ENABLE: Open-Label Study to Assess the Effect of Long-Term Prolonged-Release Fampridine (BIIB041) on Quality of Life as Reported by Participants With Multiple Sclerosis

Sponsor

Biogen (Industry)

Overall Status

Completed

CT.gov ID

NCT01480076

Collaborator

(none)

901

Enrollment

Locations

Arm

Duration (Months)

15.3

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of the study is to assess the effect of long-term treatment with prolonged-release fampridine (BIIB041) 10 mg twice daily on the physical component scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) as reported by treatment responders. The secondary objectives of this study are to compare the change in the PCS of the SF-36 between treatment responders and non-responders, to evaluate change from baseline in additional quality of life measures among treatment responders as well as changes from baseline in treatment responders versus non-responders and to assess the safety and tolerability of prolonged-release fampridine 10 mg twice daily.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Fampridine	Phase 4

Detailed Description

This study has 2 components: a 4-week run-in period during which participants are treated with prolonged-release fampridine and undergo subjective and objective assessments of walking ability, the results of which are used to determine who responded to study treatment, and an observational period, during which treatment responders will continue prolonged-release fampridine treatment. The participants who do not meet the criteria to continue study treatment will be offered the opportunity to continue study participation but will not continue prolonged-release fampridine treatment.

Study Design

Study Type:

Interventional

Actual Enrollment :

901 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-Label, Multicenter, Multinational Study to Assess the Effect of Long-Term Prolonged-Release Fampridine (BIIB041) 10 mg Twice Daily on Quality of Life as Reported by Subjects With Multiple Sclerosis

Study Start Date :

Feb 1, 2012

Actual Primary Completion Date :

Jul 1, 2013

Actual Study Completion Date :

Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: (BIIB041) Fampridine All participants take 10 mg fampridine twice daily for the first 4 weeks. If deemed a treatment responder, a participant continues 10 mg fampridine twice daily for 44 weeks. Treatment non-responders can continue without treatment by completing quality of life questionnaires.	Drug: Fampridine Supplied as a 10 mg twice daily tablet and taken twice daily. Doses must be spaced at least 12 hours apart. Other Names: Fampyra BIIB041 Ampyra dalfampridine fampridine prolonged-release tablets

Arm

Intervention/Treatment

Experimental: (BIIB041) Fampridine

All participants take 10 mg fampridine twice daily for the first 4 weeks. If deemed a treatment responder, a participant continues 10 mg fampridine twice daily for 44 weeks. Treatment non-responders can continue without treatment by completing quality of life questionnaires.

Drug: Fampridine

Supplied as a 10 mg twice daily tablet and taken twice daily. Doses must be spaced at least 12 hours apart.

Other Names:

Fampyra

BIIB041

Ampyra

dalfampridine

fampridine prolonged-release tablets

Outcome Measures

Primary Outcome Measures

Change From Baseline in the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) At Months 3, 6, 9, and 12: Responders [Baseline, Months 3, 6, 9, 12]
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. Within-group least squares means are presented.

Secondary Outcome Measures

Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders [Baseline, Months 3, 6, 9, 12]
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). In contrast to the primary endpoint, this analysis was done using data from both responder and non-responder groups; therefore, 'responder group' and 'visit by responder group interaction' were included as fixed effects.
Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12 [Baseline, Months 3, 6, 9, 12]
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12 [Baseline, Months 3, 6, 9, 12]
The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 [Baseline, Months 3, 6, 9, 12]
The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12 [Baseline, Months 3, 6, 9, 12]
The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12 [Baseline, Months 3, 6, 9, 12]
EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 [Baseline, Months 3, 6, 9, 12]
EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying United Kingdom (UK) weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12 [Baseline, Months 3, 6, 9, 12]
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 [Baseline, Months 3, 6, 9, 12]
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 [Baseline, Months 3, 6, 9, 12]
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 [Baseline, Months 3, 6, 9, 12]
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders [Baseline, Months 3, 6, 9, and 12]
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders [Baseline, Months 3, 6, 9, and 12]
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders [Baseline, Months 3, 6, 9, and 12]
The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders [Baseline, Months 3, 6, 9, and 12]
The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders [Baseline, Months 3, 6, 9, and 12]
The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders [Baseline, Months 3, 6, 9, and 12]
EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders [Baseline, Months 3, 6, 9, and 12]
EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying UK weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders [Baseline, Months 3, 6, 9, and 12]
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders [Baseline, Months 3, 6, 9, and 12]
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders [Baseline, Months 3, 6, 9, and 12]
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders [Baseline, Months 3, 6, 9, and 12]
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [Baseline, Months 3, 6, 9, 12]
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [Baseline, Months 3, 6, 9, 12]
The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [Baseline, Months 3, 6, 9, and 12]
The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [Months 3, 6, 9, and 12]
The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [Baseline, Months 3, 6, 9, 12]
The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [Baseline, Months 3, 6, 9, 12]
EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [Baseline, Months 3, 6, 9, 12]
EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying UK weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [Baseline, Months 3, 6, 9, and 12]
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [Baseline, Months 3, 6, 9, and 12]
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [Baseline, Months 3, 6, 9, and 12]
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [Baseline, Months 3, 6, 9, and 12]
WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [From signing of Informed Consent (SAEs) or from first dose of study treatment (AEs) through Week 50 or Early Termination (14 +/- 7 days after last dose)]
AE: any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. SAE: any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the subject at immediate risk of death (a life threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, could have jeopardized the subject or may have required intervention to prevent one of the other outcomes listed in the definition above.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Key Inclusion Criteria:

Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations.
Must have a diagnosis of primary-progressive, secondary-progressive, progressive-remitting, or relapsing-remitting multiple sclerosis (MS) per revised McDonald Committee criteria ([Polman et al, 2011]) as defined by Lublin and Reingold [Lublin and Reingold 1996] of at least 3 months duration.
Have a walking impairment as determined by the Investigator.
Able to perform the Timed 25-foot Walk Test with or without a walking aid.
Female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment.
Able to understand and comply with the requirements of the protocol.

Key Exclusion Criteria:

Known allergy to pyridine-containing substances or to any of the inactive ingredients in the prolonged-release fampridine tablet.
Any history of seizure, epilepsy, or other convulsive disorder, with the exception of febrile seizures in childhood.
An estimated creatinine clearance of <80 mL/minute.
Subject needs to take medicinal products that are inhibitors of organic cation transporter 2 (OCT2 [e.g., cimetidine]).
Female subjects who are currently pregnant or who are considering becoming pregnant while participating in the study.
Female subjects who are currently breastfeeding.
Previous exposure to fampridine.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country
1	Research Site	Concord	New South Wales	Australia
2	Research Site	Kogarah	New South Wales	Australia
3	Research Site	Liverpool	New South Wales	Australia
4	Research Site	New Lambton Heights	New South Wales	Australia
5	Research Site	Auchenflower	Queensland	Australia
6	Research Site	Box Hill	Victoria	Australia
7	Research Site	Clayton	Victoria	Australia
8	Research Site	Fitzroy	Victoria	Australia
9	Research Site	Heidelberg	Victoria	Australia
10	Research Site	Brasschaat		Belgium
11	Research Site	Brussels		Belgium
12	Research Site	Diepenbeek		Belgium
13	Research Site	Fraiture-en-Condroz		Belgium
14	Research Site	Gent		Belgium
15	Research Site	Liege		Belgium
16	Research Site	Melsbroek		Belgium
17	Research Site	Overpelt		Belgium
18	Research Site	Sijsele-Damme		Belgium
19	Research Site	Wilrijk		Belgium
20	Research Site	Copenhagen		Denmark
21	Research Site	Nice	Alpes-Maritimes	France
22	Research Site	Strasbourg	Bas-Rhin	France
23	Research Site	Caen	Calvados	France
24	Research Site	Bordeaux Cedex	Gironde 5	France
25	Research Site	Rennes	Ille-et-Vilaine	France
26	Research Site	Nantes	Loire-Atlantique 6	France
27	Research Site	Reims	Marne	France
28	Research Site	Clemont-Ferrand	Rhone	France
29	Research Site	Paris	Seine-Saint-Denis 14	France
30	Research Site	Amiens	Somme	France
31	Research Site	Paris		France
32	Research Site	Heidenheim	Bad Wuerttemberg	Germany
33	Research Site	Kassel	Hessen	Germany
34	Research Site	Oldenburg	Niedersachsen	Germany
35	Research Site	Muenster	Nordrhein-Westfalen	Germany
36	Research Site	Berlin		Germany
37	Research Site	Erbach		Germany
38	Research Site	Hamburg		Germany
39	Research Site	Jena		Germany
40	Research Site	Osnabrueck		Germany
41	Research Site	Schwendi		Germany
42	Research Site	Bari		Italy
43	Research Site	Firenze		Italy
44	Research Site	Milano		Italy
45	Research Site	Padova		Italy
46	Research Site	Roma		Italy
47	Research Site	Eindhoven		Netherlands
48	Research Site	Hoorn		Netherlands
49	Research Site	Nijmegen		Netherlands
50	Research Site	Tilburg		Netherlands
51	Research Site	Amadora		Portugal
52	Research Site	Coimbra		Portugal
53	Research Site	Lisboa		Portugal
54	Research Site	Porto		Portugal
55	Research Site	Salford	Greater Manchester	United Kingdom
56	Research Site	Nottingham	Northamptonshire	United Kingdom
57	Research Site	Glasgow	Stirlingshire	United Kingdom
58	Research Site	Liverpool		United Kingdom
59	Research Site	London		United Kingdom

Sponsors and Collaborators

Biogen

Investigators

Study Director: Medical Director, Biogen

Study Documents (Full-Text)

None provided.

More Information

Publications

Macdonell R, Nagels G, Laplaud DA, Pozzilli C, de Jong B, Martins da Silva A, Nicholas R, Lechner-Scott J, Gaebler JA, Agarwal S, Wang P, Yeh M, Hovenden M, Soelberg Sørensen P. Improved patient-reported health impact of multiple sclerosis: The ENABLE study of PR-fampridine. Mult Scler. 2016 Jun;22(7):944-54. doi: 10.1177/1352458515606809. Epub 2015 Oct 7.

Responsible Party:

Biogen

ClinicalTrials.gov Identifier:

NCT01480076

Other Study ID Numbers:

218MS403

First Posted:

Nov 28, 2011

Last Update Posted:

Mar 21, 2017

Last Verified:

Feb 1, 2017

Keywords provided by Biogen

Quality of Life

Multiple Sclerosis

Additional relevant MeSH terms:

Multiple Sclerosis

Sclerosis

4-Aminopyridine

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail

Arm/Group Title	Fampridine
Arm/Group Description	All participants took 10 mg fampridine twice daily for the first 4 weeks. If deemed a treatment responder, the participant continued 10 mg fampridine twice daily for 44 weeks. Treatment non-responders continued without treatment by completing quality of life questionnaires.
Period Title: Overall Study
STARTED	901
Intent to Treat Population	835
COMPLETED	611
NOT COMPLETED	290

Baseline Characteristics

Arm/Group Title	Responder	Non-responder	Total
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. If deemed a treatment responder, the participant continued 10 mg fampridine twice daily for 44 weeks.	Participants took 10 mg fampridine twice daily for the first 4 weeks. Treatment non-responders continued without treatment by completing quality of life questionnaires.	Total of all reporting groups
Overall Participants	707	128	835
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.3 (9.70)	50.5 (10.0)	49.5 (9.75)
Sex: Female, Male (Count of Participants)
Female	402 56.9%	79 61.7%	481 57.6%
Male	305 43.1%	49 38.3%	354 42.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) At Months 3, 6, 9, and 12: Responders
Description	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. Within-group least squares means are presented.
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.
Measure Participants	666
Month 3	4.2 (0.36)
Month 6	3.4 (0.38)
Month 9	3.2 (0.37)
Month 12	2.9 (0.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3: Mixed effect model for repeated measures with visit, baseline PCS score, baseline Expanded Disability Status Scale (EDSS) score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	within group p-value
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6: Mixed effect model for repeated measures with visit, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	within group p-value
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Difference of Month 3 versus Month 6: Mixed effect model for repeated measures with visit, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	0.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.22
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9: Mixed effect model for repeated measures with visit, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	within-group p-value
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Difference of Month 6 versus Month 9: Mixed effect model for repeated measures with visit, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2531
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	0.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.21
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12: Mixed effect model for repeated measures with visit, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	within group p-value
	Method	mixed effect model
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Difference of Month 9 versus Month 12: Mixed effect model for repeated measures with visit, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2299
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	0.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.21
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders
Description	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). In contrast to the primary endpoint, this analysis was done using data from both responder and non-responder groups; therefore, 'responder group' and 'visit by responder group interaction' were included as fixed effects.
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder	Non-responder
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	666	81
Overall	3.3 (0.34)	-0.4 (0.63)
Month 3	4.0 (0.36)	-0.2 (0.67)
Month 6	3.3 (0.37)	0.2 (0.77)
Month 9	3.0 (0.37)	-1.1 (0.80)
Month 12	2.8 (0.37)	-0.5 (0.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5405
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	3.7
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.58
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7272
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	4.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.64
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7484
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	3.0
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.75
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1877
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	4.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.78
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5460
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline PCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	3.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.79
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12
Description	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder	Non-responder
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	667	81
Overall	3.1 (0.53)	0.1 (0.95)
Month 3	4.2 (0.55)	-0.6 (1.03)
Month 6	3.3 (0.56)	0.6 (1.12)
Month 9	2.3 (0.58)	1.0 (1.22)
Month 12	2.5 (0.57)	-0.6 (1.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9073
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	3.0
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.89
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5542
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	4.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.99
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5810
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0140
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	2.7
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.08
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4138
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2740
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	1.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.19
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6453
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MCS score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0090
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	3.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.18
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12
Description	The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder	Non-responder
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	669	79
Overall	-10.3 (0.99)	-2.1 (1.79)
Month 3	-13.0 (1.00)	-2.1 (1.83)
Month 6	-10.6 (1.03)	-3.0 (1.99)
Month 9	-8.9 (1.06)	-0.3 (2.19)
Month 12	-8.6 (1.06)	-2.8 (2.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2475
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-8.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.66
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2422
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-10.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.72
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1262
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-7.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.90
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8858
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-8.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.12
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2111
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 physical score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0072
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-5.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.16
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12
Description	The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder	Non-responder
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	669	79
Overall	-7.8 (0.97)	-1.0 (1.77)
Month 3	-9.6 (1.01)	-0.2 (1.91)
Month 6	-7.7 (1.03)	-2.6 (2.06)
Month 9	-6.8 (1.06)	-0.8 (2.26)
Month 12	-7.0 (1.06)	-0.5 (2.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5577
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-6.7
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.64
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9365
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-9.4
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.82
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2008
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0102
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-5.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.98
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7134
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0066
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-6.0
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.20
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8202
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder status, visit by responder status interaction, baseline MSIS-29 psychological score, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0049
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-6.4
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.28
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12
Description	The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder	Non-responder
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	498	45
Overall	-1.4 (0.22)	0.8 (0.56)
Month 3	-2.3 (0.23)	-0.4 (0.58)
Month 6	-1.4 (0.25)	0.8 (0.70)
Month 9	-1.2 (0.25)	1.8 (0.73)
Month 12	-0.8 (0.26)	1.1 (0.83)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1324
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.56
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4759
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0016
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.59
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2489
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0017
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-2.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.71
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0126
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-3.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.75
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0033
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1758
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the total activity limitation score of PRIMUS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0246
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.84
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12
Description	EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder	Non-responder
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	659	79
Overall	6.7 (0.95)	-4.4 (1.73)
Month 3	8.0 (1.00)	-3.2 (1.91)
Month 6	6.1 (1.02)	-3.6 (2.06)
Month 9	6.3 (1.04)	-4.9 (2.21)
Month 12	6.3 (1.05)	-6.0 (2.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0111
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder Versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	11.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.61
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0970
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder Versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	11.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.82
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0789
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder Versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	9.7
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.00
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0284
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder Versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	11.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.16
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0108
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder Versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of the current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	12.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.29
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12
Description	EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying United Kingdom (UK) weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder	Non-responder
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	661	78
Overall	0.05 (0.01)	0.00 (0.02)
Month 3	0.07 (0.01)	0.01 (0.02)
Month 6	0.05 (0.01)	0.01 (0.02)
Month 9	0.04 (0.01)	0.01 (0.03)
Month 12	0.04 (0.01)	-0.01 (0.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8392
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0162
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	0.04
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.02
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6956
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0042
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	0.06
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.02
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7949
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0679
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	0.04
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.02
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0027
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8053
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2638
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	0.03
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.03
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8502
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of current health state of EQ-5D scores, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0917
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	0.05
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.03
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12
Description	WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder	Non-responder
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	191	14
Overall	-2.5 (1.87)	-8.3 (4.60)
Month 3	-3.0 (2.15)	-4.0 (5.81)
Month 6	-5.3 (1.95)	-7.6 (5.07)
Month 9	-1.1 (2.31)	-9.6 (7.77)
Month 12	-0.7 (2.24)	-12.1 (6.54)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1795
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0715
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2065
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	5.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 4.60
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1649
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4894
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8611
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	1.0
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.89
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0073
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1343
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6468
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	2.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.09
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6441
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2176
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2814
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	8.5
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.91
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7533
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0653
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage of work time missed due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0876
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	11.4
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.65
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12
Description	WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder	Non-responder
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	217	16
Overall	-4.2 (1.88)	-8.4 (4.56)
Month 3	-6.9 (2.09)	-1.8 (5.53)
Month 6	-6.5 (2.01)	-5.6 (5.38)
Month 9	-3.0 (2.18)	-17.9 (6.80)
Month 12	-0.3 (2.22)	-8.4 (6.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0281
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0654
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3400
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	4.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 4.47
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7490
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3592
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-5.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.53
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0015
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2967
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8735
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.34
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1696
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0089
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0297
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	14.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.83
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8806
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2170
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage impairment while working due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2392
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	8.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.86
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12
Description	WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder	Non-responder
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	186	13
Overall	-5.2 (2.24)	-8.7 (5.69)
Month 3	-7.7 (2.49)	-4.5 (6.57)
Month 6	-7.8 (2.43)	-2.9 (6.73)
Month 9	-2.4 (2.86)	-15.9 (9.83)
Month 12	-2.9 (2.47)	-11.7 (7.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0219
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1259
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5312
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	3.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.68
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0022
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4968
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6283
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.64
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0016
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6631
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4770
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-4.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.77
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4027
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1077
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1781
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	13.5
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 9.98
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2422
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0994
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of percentage overall work impairment due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2194
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	8.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.13
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12
Description	WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder	Non-responder
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	650	77
Overall	-11.4 (1.31)	-4.1 (2.37)
Month 3	-13.5 (1.42)	-3.1 (2.83)
Month 6	-12.3 (1.43)	-4.7 (2.94)
Month 9	-10.4 (1.44)	-4.1 (3.08)
Month 12	-9.2 (1.45)	-4.4 (3.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0860
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-7.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.20
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2777
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-10.4
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.76
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1078
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0082
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-7.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.87
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1838
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0364
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-6.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.02
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1714
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder versus Non-responder: Mixed effect model for repeated measures with visit, responder group, visit and responder group interaction, baseline of regular activity productivity loss due to MS, baseline EDSS score, MS disease type, age, gender, total number of relapses experienced within the past 12 months and country as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1259
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	-4.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.14
	Estimation Comments

13. Secondary Outcome

Title	Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders
Description	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Relapsing-Remitting MS	Secondary-Progressive MS	Primary-Progressive MS	Progressive-Relapsing MS
Arm/Group Description	Participants in the Responder group with relapsing-remitting MS (RRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with secondary-progressive MS (SPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with primary-progressive MS (PPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with progressive-relapsing MS (PRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.
Measure Participants	256	264	115	31
Overall	4.5 (0.39)	3.8 (0.38)	2.5 (0.49)	3.2 (0.89)
Month 3	5.5 (0.42)	4.5 (0.41)	3.1 (0.55)	2.7 (1.01)
Month 6	4.4 (0.46)	3.9 (0.45)	2.3 (0.61)	3.9 (1.13)
Month 9	4.2 (0.45)	3.2 (0.45)	3.0 (0.60)	3.2 (1.12)
Month 12	4.0 (0.45)	3.4 (0.45)	1.7 (0.61)	2.9 (1.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, RRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, SPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, PPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, PRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0069
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0040
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0047
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline PCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0118
	Comments
	Method	mixed effect model
	Comments

14. Secondary Outcome

Title	Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders
Description	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Relapsing-Remitting MS	Secondary-Progressive MS	Primary-Progressive MS	Progressive-Relapsing MS
Arm/Group Description	Participants in the Responder group with relapsing-remitting MS (RRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with secondary-progressive MS (SPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with primary-progressive MS (PPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with progressive-relapsing MS (PRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.
Measure Participants	256	264	116	31
Overall	4.0 (0.59)	3.0 (0.58)	3.2 (0.74)	2.0 (1.36)
Month 3	4.9 (0.64)	4.5 (0.63)	3.9 (0.83)	2.6 (1.54)
Month 6	4.3 (0.67)	2.9 (0.66)	3.5 (0.89)	2.9 (1.65)
Month 9	3.1 (0.70)	2.1 (0.69)	2.7 (0.93)	2.0 (1.74)
Month 12	3.5 (0.68)	2.6 (0.67)	2.5 (0.89)	0.5 (1.68)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, RRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, SPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, PPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, PRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1398
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0935
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0760
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0019
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0037
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2489
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0052
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline MCS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7714
	Comments
	Method	mixed effect model
	Comments

15. Secondary Outcome

Title	Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders
Description	The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Relapsing-Remitting MS	Secondary-Progressive MS	Primary-Progressive MS	Progressive-Relapsing MS
Arm/Group Description	Participants in the Responder group with relapsing-remitting MS (RRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with secondary-progressive MS (SPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with primary-progressive MS (PPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with progressive-relapsing MS (PRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.
Measure Participants	256	264	118	31
Overall	-12.1 (1.12)	-10.3 (1.09)	-8.3 (1.40)	-12.5 (2.58)
Month 3	-15.0 (1.16)	-13.3 (1.13)	-10.6 (1.47)	-12.6 (2.72)
Month 6	-12.0 (1.22)	-10.9 (1.19)	-8.4 (1.58)	-14.9 (2.94)
Month 9	-10.5 (1.27)	-8.9 (1.25)	-7.9 (1.67)	-10.4 (3.13)
Month 12	-10.9 (1.27)	-8.2 (1.25)	-6.2 (1.66)	-11.9 (3.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 physical score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	mixed effect model
	Comments

16. Secondary Outcome

Title	Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders
Description	The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Relapsing-Remitting MS	Secondary-Progressive MS	Primary-Progressive MS	Progressive-Relapsing MS
Arm/Group Description	Participants in the Responder group with relapsing-remitting MS (RRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with secondary-progressive MS (SPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with primary-progressive MS (PPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with progressive-relapsing MS (PRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.
Measure Participants	257	263	118	31
Overall	-9.4 (1.09)	-6.5 (1.07)	-8.3 (1.37)	-7.5 (2.53)
Month 3	-11.2 (1.17)	-8.9 (1.15)	-9.1 (1.51)	-8.6 (2.80)
Month 6	-8.8 (1.23)	-6.8 (1.22)	-8.7 (1.62)	-7.9 (3.06)
Month 9	-8.3 (1.29)	-5.1 (1.27)	-8.2 (1.70)	-8.3 (3.21)
Month 12	-9.3 (1.29)	-5.3 (1.28)	-7.4 (1.71)	-5.1 (3.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0032
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0021
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0097
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0103
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline MSIS-29 psychological score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1227
	Comments
	Method	mixed effect model
	Comments

17. Secondary Outcome

Title	Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders
Description	The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Relapsing-Remitting MS	Secondary-Progressive MS	Primary-Progressive MS	Progressive-Relapsing MS
Arm/Group Description	Participants in the Responder group with relapsing-remitting MS (RRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with secondary-progressive MS (SPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with primary-progressive MS (PPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with progressive-relapsing MS (PRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.
Measure Participants	198	187	87	26
Overall	-2.5 (0.29)	-1.1 (0.27)	-0.5 (0.39)	-1.7 (0.70)
Month 3	-3.2 (0.31)	-2.1 (0.29)	-1.6 (0.42)	-1.9 (0.77)
Month 6	-2.3 (0.35)	-1.3 (0.34)	-0.8 (0.48)	-1.6 (0.88)
Month 9	-2.4 (0.35)	-0.7 (0.33)	-0.3 (0.48)	-2.0 (0.88)
Month 12	-2.0 (0.37)	-0.5 (0.36)	0.7 (0.52)	-1.2 (0.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, RRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, SPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, PPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1754
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, PRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0192
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0157
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1012
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0749
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0455
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4699
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0235
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1978
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1977
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline of the total ALS score, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2250
	Comments
	Method	mixed effect model
	Comments

18. Secondary Outcome

Title	Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders
Description	EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Relapsing-Remitting MS	Secondary-Progressive MS	Primary-Progressive MS	Progressive-Relapsing MS
Arm/Group Description	Participants in the Responder group with relapsing-remitting MS (RRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with secondary-progressive MS (SPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with primary-progressive MS (PPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with progressive-relapsing MS (PRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.
Measure Participants	256	258	116	29
Overall	8.8 (1.06)	6.5 (1.04)	6.7 (1.34)	4.7 (2.53)
Month 3	10.1 (1.17)	8.2 (1.15)	7.3 (1.53)	4.6 (2.91)
Month 6	8.0 (1.22)	6.1 (1.21)	6.0 (1.63)	4.1 (3.12)
Month 9	8.2 (1.25)	5.6 (1.24)	7.9 (1.66)	5.5 (3.22)
Month 12	8.8 (1.26)	6.1 (1.26)	5.5 (1.70)	4.5 (3.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0649
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1138
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1850
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0887
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1853
	Comments
	Method	mixed effect model
	Comments

19. Secondary Outcome

Title	Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders
Description	EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying UK weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Relapsing-Remitting MS	Secondary-Progressive MS	Primary-Progressive MS	Progressive-Relapsing MS
Arm/Group Description	Participants in the Responder group with relapsing-remitting MS (RRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with secondary-progressive MS (SPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with primary-progressive MS (PPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with progressive-relapsing MS (PRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.
Measure Participants	254	262	114	31
Overall	0.05 (0.01)	0.04 (0.01)	0.05 (0.02)	0.07 (0.03)
Month 3	0.07 (0.01)	0.06 (0.01)	0.05 (0.02)	0.06 (0.03)
Month 6	0.04 (0.01)	0.05 (0.01)	0.05 (0.02)	0.09 (0.04)
Month 9	0.05 (0.01)	0.02 (0.01)	0.04 (0.02)	0.02 (0.04)
Month 12	0.04 (0.01)	0.03 (0.01)	0.05 (0.02)	0.10 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0027
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0167
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0024
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0669
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0018
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0190
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0106
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0009
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1937
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0445
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6475
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0097
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0386
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0219
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline of the current health state of EQ-5D scores, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0076
	Comments
	Method	mixed effect model
	Comments

20. Secondary Outcome

Title	Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders
Description	WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Relapsing-Remitting MS	Secondary-Progressive MS	Primary-Progressive MS	Progressive-Relapsing MS
Arm/Group Description	Participants in the Responder group with relapsing-remitting MS (RRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with secondary-progressive MS (SPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with primary-progressive MS (PPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with progressive-relapsing MS (PRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.
Measure Participants	93	55	34	9
Overall	-2.9 (2.01)	-1.5 (2.51)	-2.5 (2.86)	-4.0 (5.82)
Month 3	-3.1 (2.49)	-2.6 (3.18)	-3.3 (3.81)	-1.1 (8.51)
Month 6	-6.4 (2.23)	-5.3 (2.79)	-3.3 (3.15)	-2.3 (6.29)
Month 9	-1.9 (2.86)	2.0 (3.68)	-1.1 (4.44)	-10.0 (8.77)
Month 12	-0.3 (2.67)	-0.1 (3.44)	-2.2 (4.12)	-2.7 (8.24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1471
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5503
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3854
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4893
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2166
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4149
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3849
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8980
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0046
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0594
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2975
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7155
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5070
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5848
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8020
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2540
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9057
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9679
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5875
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of work time missed due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7440
	Comments
	Method	mixed effect model
	Comments

21. Secondary Outcome

Title	Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders
Description	WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Relapsing-Remitting MS	Secondary-Progressive MS	Primary-Progressive MS	Progressive-Relapsing MS
Arm/Group Description	Participants in the Responder group with relapsing-remitting MS (RRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with secondary-progressive MS (SPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with primary-progressive MS (PPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with progressive-relapsing MS (PRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.
Measure Participants	106	62	40	9
Overall	-5.8 (1.95)	-4.2 (2.43)	0.8 (2.78)	-7.3 (5.95)
Month 3	-8.6 (2.28)	-8.0 (2.88)	-1.7 (3.38)	-2.9 (7.57)
Month 6	-6.7 (2.20)	-8.7 (2.79)	-2.5 (3.26)	-8.3 (6.88)
Month 9	-5.0 (2.49)	-1.8 (3.17)	0.5 (3.85)	-4.9 (8.51)
Month 12	-2.9 (2.56)	1.4 (3.35)	6.8 (3.95)	-13.1 (8.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0032
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0828
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7756
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2200
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0061
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6258
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6987
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0025
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0021
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4385
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2275
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0446
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5757
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8936
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5675
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2539
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6673
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0849
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of impairment while working due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1187
	Comments
	Method	mixed effect model
	Comments

22. Secondary Outcome

Title	Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders
Description	WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Relapsing-Remitting MS	Secondary-Progressive MS	Primary-Progressive MS	Progressive-Relapsing MS
Arm/Group Description	Participants in the Responder group with relapsing-remitting MS (RRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with secondary-progressive MS (SPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with primary-progressive MS (PPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with progressive-relapsing MS (PRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.
Measure Participants	92	52	33	9
Overall	-7.5 (2.41)	-6.8 (3.09)	-0.8 (3.54)	-6.5 (6.97)
Month 3	-10.7 (2.74)	-10.4 (3.56)	-1.7 (4.18)	2.9 (9.51)
Month 6	-9.2 (2.81)	-11.9 (3.60)	-3.3 (4.22)	-6.5 (8.10)
Month 9	-4.9 (3.49)	-2.6 (4.61)	1.2 (5.62)	-9.7 (11.15)
Month 12	-5.3 (2.84)	-2.1 (3.73)	0.4 (4.42)	-12.6 (8.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0022
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0299
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8135
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3526
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0039
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6924
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7639
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0013
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4340
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4224
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1628
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5666
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8315
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3852
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0652
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5719
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9237
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of overall work impairment due to MS, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1310
	Comments
	Method	mixed effect model
	Comments

23. Secondary Outcome

Title	Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders
Description	WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Relapsing-Remitting MS	Secondary-Progressive MS	Primary-Progressive MS	Progressive-Relapsing MS
Arm/Group Description	Participants in the Responder group with relapsing-remitting MS (RRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with secondary-progressive MS (SPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with primary-progressive MS (PPMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants in the Responder group with progressive-relapsing MS (PRMS). Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.
Measure Participants	251	252	116	31
Overall	-14.9 (1.49)	-9.8 (1.47)	-7.1 (1.86)	-12.2 (3.39)
Month 3	-16.2 (1.74)	-13.4 (1.72)	-8.7 (2.29)	-11.0 (4.28)
Month 6	-15.1 (1.76)	-11.1 (1.76)	-9.0 (2.35)	-14.2 (4.35)
Month 9	-14.9 (1.79)	-7.5 (1.78)	-7.1 (2.35)	-10.8 (4.46)
Month 12	-13.5 (1.79)	-7.1 (1.79)	-3.7 (2.37)	-13.0 (4.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0102
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0026
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0161
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, RRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, SPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, PPMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1151
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, PRMS. Mixed effect model for repeated measures with visit, baseline of percentage of regular activity productivity loss, MS type, age, gender, country, visit and MS type interaction, baseline EDSS score and total number of relapses experienced within the past 12 months as fixed effects. An unstructured covariance was used to model within-participant error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0040
	Comments
	Method	mixed effect model
	Comments

24. Secondary Outcome

Title	Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
Description	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder: Taking Additional MS Therapy	Non-responder: Taking Additional MS Therapy	Responder: Not Taking Additional MS Therapy	Non-responder: Not Taking Additional MS Therapy
Arm/Group Description	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	521	58	145	23
Overall	3.1 (0.36)	-0.3 (0.71)	3.9 (0.48)	-0.6 (1.08)
Month 3	4.0 (0.38)	0.1 (0.77)	4.1 (0.53)	-1.2 (1.19)
Month 6	3.1 (0.40)	0.6 (0.89)	3.9 (0.58)	-0.8 (1.35)
Month 9	2.7 (0.40)	-1.2 (0.91)	4.0 (0.58)	-0.7 (1.46)
Month 12	2.5 (0.40)	-0.8 (0.94)	3.6 (0.58)	0.2 (1.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6769
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5780
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	3.4
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.68
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	4.5
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.10
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8886
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3221
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	3.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.75
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	5.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.23
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4668
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5695
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0058
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	2.4
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.88
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	4.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.40
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2040
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6306
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder (Taking Additional MS Therapy) versus Non- responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	3.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.90
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0020
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	4.7
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.51
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4052
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8626
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	3.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.93
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline PCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0263
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	3.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.49
	Estimation Comments

25. Secondary Outcome

Title	Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
Description	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder: Taking Additional MS Therapy	Non-responder: Taking Additional MS Therapy	Responder: Not Taking Additional MS Therapy	Non-responder: Not Taking Additional MS Therapy
Arm/Group Description	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	522	58	145	23
Overall	2.8 (0.56)	-0.1 (1.09)	3.9 (0.74)	0.6 (1.64)
Month 3	4.0 (0.59)	-1.3 (1.18)	4.8 (0.81)	1.1 (1.82)
Month 6	3.0 (0.60)	0.2 (1.29)	4.1 (0.85)	1.5 (1.96)
Month 9	2.1 (0.62)	1.3 (1.40)	2.8 (0.89)	0.0 (2.24)
Month 12	2.1 (0.61)	-0.7 (1.40)	3.9 (0.87)	-0.3 (2.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8999
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7156
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0050
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	2.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.03
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0490
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	3.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.68
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2740
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5556
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	5.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.15
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0476
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	3.7
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.88
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8627
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4312
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0305
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	2.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.27
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2059
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	2.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.03
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3685
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0016
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9862
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5561
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	0.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.38
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2281
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	2.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.32
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0006
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6004
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9040
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0401
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	2.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.38
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the 2-way and 3-way interactions among them, baseline MCS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0651
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	4.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.23
	Estimation Comments

26. Secondary Outcome

Title	Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
Description	The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder: Taking Additional MS Therapy	Non-responder: Taking Additional MS Therapy	Responder: Not Taking Additional MS Therapy	Non-responder: Not Taking Additional MS Therapy
Arm/Group Description	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	524	57	145	22
Overall	-9.6 (1.05)	-1.5 (2.03)	-12.2 (1.38)	-3.2 (3.10)
Month 3	-12.6 (1.07)	-1.4 (2.08)	-14.0 (1.43)	-4.0 (3.22)
Month 6	-10.0 (1.10)	-2.2 (2.28)	-12.2 (1.52)	-5.2 (3.47)
Month 9	-8.0 (1.13)	-0.4 (2.48)	-11.8 (1.61)	0.5 (4.02)
Month 12	-7.8 (1.13)	-2.1 (2.57)	-11.1 (1.61)	-4.3 (3.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4540
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2949
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-8.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.93
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0046
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-9.0
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.16
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-12.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.07
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5020
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2157
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-11.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.00
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0026
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-10.0
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.30
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3435
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1357
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-7.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.22
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0511
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-7.0
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.58
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8703
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9049
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0019
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-7.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.44
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0033
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-12.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 4.15
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4087
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2755
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0251
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-5.7
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.52
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 physical score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0989
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-6.7
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 4.08
	Estimation Comments

27. Secondary Outcome

Title	Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
Description	The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder: Taking Additional MS Therapy	Non-responder: Taking Additional MS Therapy	Responder: Not Taking Additional MS Therapy	Non-responder: Not Taking Additional MS Therapy
Arm/Group Description	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	525	57	144	22
Overall	-7.1 (1.02)	-0.3 (2.00)	-9.7 (1.36)	-2.8 (3.06)
Month 3	-9.0 (1.07)	0.2 (2.17)	-11.1 (1.49)	-1.0 (3.39)
Month 6	-7.1 (1.10)	-2.6 (2.37)	-9.5 (1.56)	-2.6 (3.60)
Month 9	-6.1 (1.13)	-0.2 (2.57)	-8.9 (1.64)	-2.4 (4.22)
Month 12	-6.2 (1.13)	1.3 (2.70)	-9.1 (1.67)	-5.1 (4.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8767
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3673
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-6.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.91
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0273
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-6.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.12
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9091
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7718
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-9.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.11
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0038
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-10.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.50
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2720
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4767
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0553
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-4.5
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.32
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0632
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-6.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.73
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder (Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9398
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, Non-responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5655
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0204
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-5.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.54
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1414
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-6.4
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 4.37
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6279
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2239
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0049
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-7.5
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.67
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline MSIS-29 psychological score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3457
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-4.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 4.32
	Estimation Comments

28. Secondary Outcome

Title	Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
Description	The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder: Taking Additional MS Therapy	Non-responder: Taking Additional MS Therapy	Responder: Not Taking Additional MS Therapy	Non-responder: Not Taking Additional MS Therapy
Arm/Group Description	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	395	33	103	12
Overall	-1.3 (0.24)	0.8 (0.63)	-1.9 (0.37)	0.8 (1.11)
Month 3	-2.1 (0.25)	-0.5 (0.67)	-2.9 (0.40)	-0.0 (1.14)
Month 6	-1.2 (0.27)	0.6 (0.81)	-2.1 (0.46)	1.3 (1.33)
Month 9	-1.1 (0.27)	2.0 (0.82)	-1.6 (0.46)	1.1 (1.67)
Month 12	-0.7 (0.29)	1.1 (0.93)	-1.0 (0.50)	1.0 (1.81)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2087
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4487
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0013
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.64
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0188
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-2.7
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.15
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4243
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9989
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0207
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.68
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0161
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-2.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.18
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4256
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3313
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0238
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.83
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0150
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-3.4
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.39
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0171
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5146
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-3.0
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.84
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1224
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-2.7
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.72
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0168
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2272
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0570
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5832
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0561
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.94
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the total ALS score, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2971
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.86
	Estimation Comments

29. Secondary Outcome

Title	Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
Description	EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder: Taking Additional MS Therapy	Non-responder: Taking Additional MS Therapy	Responder: Not Taking Additional MS Therapy	Non-responder: Not Taking Additional MS Therapy
Arm/Group Description	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	518	58	141	21
Overall	6.0 (1.00)	-5.8 (1.95)	8.6 (1.33)	-0.8 (3.04)
Month 3	7.6 (1.06)	-3.9 (2.16)	8.6 (1.49)	-1.2 (3.46)
Month 6	5.2 (1.09)	-5.6 (2.35)	8.6 (1.56)	1.5 (3.72)
Month 9	5.5 (1.11)	-6.1 (2.51)	8.7 (1.62)	-1.8 (4.13)
Month 12	5.5 (1.12)	-7.7 (2.67)	8.7 (1.67)	-1.5 (4.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0029
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8041
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	11.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 1.85
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0026
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	9.4
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.10
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0689
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7182
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	11.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.10
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0061
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	9.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.57
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0179
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6911
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	10.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.31
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0666
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	7.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.85
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0158
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6684
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	11.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.49
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0141
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	10.5
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 4.28
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0042
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7329
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	13.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.65
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0242
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	10.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 4.49
	Estimation Comments

30. Secondary Outcome

Title	Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
Description	EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying UK weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder: Taking Additional MS Therapy	Non-responder: Taking Additional MS Therapy	Responder: Not Taking Additional MS Therapy	Non-responder: Not Taking Additional MS Therapy
Arm/Group Description	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	519	56	142	22
Overall	0.04 (0.01)	-0.00 (0.02)	0.06 (0.02)	0.02 (0.03)
Month 3	0.07 (0.01)	0.02 (0.02)	0.07 (0.02)	-0.02 (0.04)
Month 6	0.05 (0.01)	-0.00 (0.03)	0.05 (0.02)	0.03 (0.04)
Month 9	0.03 (0.01)	-0.00 (0.03)	0.06 (0.02)	0.02 (0.05)
Month 12	0.03 (0.01)	-0.03 (0.03)	0.07 (0.02)	0.04 (0.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9151
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6128
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0331
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	0.05
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.02
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1919
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	0.05
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.04
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4481
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5454
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0516
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	0.05
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.02
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0175
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	0.09
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.04
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9371
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0056
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5475
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0699
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	0.05
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.03
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5870
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	0.02
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.05
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0245
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9926
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0027
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6368
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3358
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	0.03
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.03
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5089
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	0.03
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.05
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0141
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4280
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3827
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0748
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	0.06
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.03
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the current health state of EQ-5D index scores, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5663
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	0.03
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 0.05
	Estimation Comments

31. Secondary Outcome

Title	Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
Description	WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder: Taking Additional MS Therapy	Non-responder: Taking Additional MS Therapy	Responder: Not Taking Additional MS Therapy	Non-responder: Not Taking Additional MS Therapy
Arm/Group Description	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	149	12	42	2
Overall	-3.0 (2.10)	-11.9 (4.93)	-2.4 (2.72)	14.9 (12.11)
Month 3	-3.7 (2.43)	-8.3 (6.14)	-2.0 (3.43)	28.6 (17.71)
Month 6	-6.0 (2.21)	-10.3 (5.52)	-4.3 (2.98)	6.4 (12.11)
Month 9	-1.2 (2.60)	-12.8 (8.32)	-2.1 (4.09)	13.9 (21.98)
Month 12	-1.0 (2.53)	-16.2 (7.16)	-1.1 (3.79)	10.6 (15.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1544
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0167
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3868
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2214
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0743
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	8.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 4.96
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1601
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-17.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 12.22
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1251
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1764
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5528
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1080
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4644
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	4.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.27
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0887
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-30.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 17.91
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0071
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0640
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1552
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5979
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4444
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	4.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.58
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3863
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-10.7
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 12.27
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6352
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1265
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6161
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5280
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1769
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	11.5
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 8.51
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4743
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-16.0
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 22.24
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6901
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0245
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7707
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4989
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0387
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	15.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.31
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % work time missed due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4635
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-11.7
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 15.88
	Estimation Comments

32. Secondary Outcome

Title	Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
Description	WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder: Taking Additional MS Therapy	Non-responder: Taking Additional MS Therapy	Responder: Not Taking Additional MS Therapy	Non-responder: Not Taking Additional MS Therapy
Arm/Group Description	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	168	13	49	3
Overall	-3.1 (2.10)	-7.3 (5.00)	-6.4 (2.69)	-11.5 (10.86)
Month 3	-6.1 (2.35)	-1.0 (6.02)	-8.1 (3.24)	-3.3 (14.07)
Month 6	-5.6 (2.26)	-3.8 (5.89)	-8.0 (3.06)	-15.9 (13.27)
Month 9	-1.9 (2.44)	-19.0 (7.31)	-5.6 (3.55)	-6.0 (18.93)
Month 12	1.1 (2.49)	-5.5 (7.56)	-3.8 (3.65)	-20.7 (15.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1392
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1448
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0187
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2920
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3968
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	4.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 4.95
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6420
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	5.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 10.95
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0100
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8634
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0134
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8147
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4035
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-5.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.06
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7385
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-4.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 14.25
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0139
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5207
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0091
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2312
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7578
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.89
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5575
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	7.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 13.42
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4486
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0102
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1185
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7523
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0214
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	17.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.38
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9826
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	0.4
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 19.12
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6627
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4674
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2965
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1778
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3903
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	6.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.65
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % impairment while working due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2794
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	16.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 15.53
	Estimation Comments

33. Secondary Outcome

Title	Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
Description	WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder: Taking Additional MS Therapy	Non-responder: Taking Additional MS Therapy	Responder: Not Taking Additional MS Therapy	Non-responder: Not Taking Additional MS Therapy
Arm/Group Description	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	145	11	41	2
Overall	-4.8 (2.55)	-9.9 (6.26)	-6.7 (3.32)	1.2 (14.53)
Month 3	-7.9 (2.84)	-6.6 (6.99)	-7.1 (3.85)	18.0 (21.17)
Month 6	-7.8 (2.78)	-1.8 (7.48)	-7.7 (3.85)	-8.2 (15.87)
Month 9	-1.6 (3.22)	-18.5 (10.69)	-5.5 (5.15)	3.7 (25.71)
Month 12	-1.8 (2.81)	-12.6 (7.95)	-6.5 (4.02)	-8.6 (15.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0628
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1166
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0451
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9327
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4177
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	5.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.28
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5885
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-7.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 14.64
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0059
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3467
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0654
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.3965
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8548
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.11
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2405
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-25.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 21.35
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0056
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8105
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0470
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6067
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4309
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-6.0
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 7.56
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9761
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	0.5
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 16.09
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.6261
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0860
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2884
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8854
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1226
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	16.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 10.88
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7249
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-9.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 26.07
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5129
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1138
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1086
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.5746
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1831
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	10.8
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 8.07
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the % overall work impairment due to MS, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.8917
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	2.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 15.54
	Estimation Comments

34. Secondary Outcome

Title	Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
Description	WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).
Time Frame	Baseline, Months 3, 6, 9, and 12

Outcome Measure Data

Analysis Population Description
Participants in the intent-to-treat population (all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit) who were included in the mixed effect model for repeated measures analysis.

Arm/Group Title	Responder: Taking Additional MS Therapy	Non-responder: Taking Additional MS Therapy	Responder: Not Taking Additional MS Therapy	Non-responder: Not Taking Additional MS Therapy
Arm/Group Description	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants (not taking additional MS therapy) took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	509	56	141	21
Overall	-10.6 (1.39)	-4.2 (2.69)	-13.3 (1.83)	-3.1 (4.15)
Month 3	-12.7 (1.53)	-3.4 (3.24)	-15.7 (2.20)	-1.8 (5.15)
Month 6	-11.5 (1.54)	-6.3 (3.40)	-14.6 (2.23)	-0.5 (5.20)
Month 9	-9.8 (1.55)	-5.9 (3.50)	-12.0 (2.28)	1.6 (5.86)
Month 12	-8.5 (1.56)	-1.3 (3.70)	-10.9 (2.31)	-11.6 (5.72)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Overall, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Overall, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1152
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Overall, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.4578
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Overall, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0125
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-6.4
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 2.56
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Overall, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0158
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-10.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 4.23
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 3, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 3, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2894
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 3, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7230
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 3, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0038
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-9.3
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.20
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 3, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0097
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-13.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.37
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 6, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 6, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0628
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 6, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9232
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 6, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.1249
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-5.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.37
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 6, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0093
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-14.1
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.42
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 9, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 9, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0937
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 9, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7814
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 9, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.2561
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-3.9
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.47
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 9, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0255
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-13.6
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.07
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Responder
	Comments	Month 12, Responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Non-responder
	Comments	Month 12, Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.7241
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Progressive-Relapsing MS
	Comments	Month 12, Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0427
	Comments
	Method	mixed effect model
	Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Responder, Non-responder
	Comments	Month 12, Responder (Taking Additional MS Therapy) versus Non-responder (Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.0498
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	-7.2
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 3.67
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Primary-Progressive MS, Progressive-Relapsing MS
	Comments	Month 12, Responder (Not Taking Additional MS Therapy) versus Non-responder (Not Taking Additional MS Therapy): Mixed effect model for repeated measures with visit, responder group, additional MS therapy, the two-way and three-way interactions among them, baseline of the regular activity productivity loss, age, gender, country, baseline EDSS score and total number of relapses experienced as fixed effects. An unstructured covariance was used to model within-patient error.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value	0.9078
	Comments
	Method	mixed effect model
	Comments

Method of Estimation	Estimation Parameter	difference of LS means
	Estimated Value	0.7
	Confidence Interval	(2-Sided) % to
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.95
	Estimation Comments

35. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
Description	AE: any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. SAE: any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the subject at immediate risk of death (a life threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, could have jeopardized the subject or may have required intervention to prevent one of the other outcomes listed in the definition above.
Time Frame	From signing of Informed Consent (SAEs) or from first dose of study treatment (AEs) through Week 50 or Early Termination (14 +/- 7 days after last dose)

Outcome Measure Data

Analysis Population Description
Intent-to-treat population: all participants who received at least 1 dose of study treatment and who provided at least 1 efficacy assessment at Baseline and the 3-month visit.

Arm/Group Title	Responder	Non-responder	All Participants
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.	All participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
Measure Participants	707	128	835
AE	522 73.8%	64 50%	586 70.2%
SAE	76 10.7%	3 2.3%	79 9.5%
Severe AE	48 6.8%	2 1.6%	50 6%
Study treatment related AE	248 35.1%	37 28.9%	285 34.1%
Study treatment related SAE	7 1%	0 0%	7 0.8%
Death	2 0.3%	0 0%	2 0.2%
AE leading to study drug discontinuation	32 4.5%	8 6.3%	40 4.8%
AE leading to study discontinuation	18 2.5%	1 0.8%	19 2.3%

Adverse Events

	Responder		Non-responder		All Participants
Time Frame	From signing of Informed Consent (SAEs) or from first dose of study treatment (AEs) through Week 50 or Early Termination (14 +/- 7 days after last dose).
Adverse Event Reporting Description

Arm/Group Title	Responder		Non-responder		All Participants
Arm/Group Description	Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks.		Participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.		All participants took 10 mg fampridine twice daily for the first 4 weeks. Those deemed treatment responders continued 10 mg fampridine twice daily for 44 weeks. Those deemed treatment non-responders continued without treatment by completing quality of life questionnaires.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Responder		Non-responder		All Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	76/707 (10.7%)		3/128 (2.3%)		79/835 (9.5%)
Blood and lymphatic system disorders
Anaemia	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Microcytic Anaemia	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Cardiac disorders
Arrhythmia	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Atrial Fibrillation	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Cardiovascular Disorder	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Myocardial Infarction	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Gastrointestinal disorders
Colitis	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
General disorders
Death	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Hepatobiliary disorders
Cholecystitis Acute	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Infections and infestations
Urinary Tract Infection	3/707 (0.4%)		1/128 (0.8%)		4/835 (0.5%)
Appendicitis	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Chronic Sinusitis	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Gastrointestinal Viral Infection	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Peritonitis	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Pneumonia Influenzal	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Urosepsis	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Viral Infection	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Injury, poisoning and procedural complications
Fall	9/707 (1.3%)		0/128 (0%)		9/835 (1.1%)
Upper Limb Fracture	2/707 (0.3%)		0/128 (0%)		2/835 (0.2%)
Avulsion Fracture	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Fibula Fracture	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Hand Fracture	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Hip Fracture	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Joint Injury	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Lower Limb Fracture	0/707 (0%)		1/128 (0.8%)		1/835 (0.1%)
Traumatic Intracranial Haemorrhage	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Wound	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Wrist Fracture	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Metabolism and nutrition disorders
Fluid Retention	0/707 (0%)		1/128 (0.8%)		1/835 (0.1%)
Musculoskeletal and connective tissue disorders
Bursitis	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Cervical Spinal Stenosis	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Exostosis	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Foot Deformity	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Musculoskeletal Pain	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Musculoskeletal Stiffness	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Rotator Cuff Syndrome	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Synovial Cyst	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Vertebral Foraminal Stenosis	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Melanoma Stage IV	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Uterine Leiomyoma	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Nervous system disorders
Multiple Sclerosis Relapse	19/707 (2.7%)		0/128 (0%)		19/835 (2.3%)
Grand Mal Convulsion	2/707 (0.3%)		0/128 (0%)		2/835 (0.2%)
Multiple Sclerosis	2/707 (0.3%)		0/128 (0%)		2/835 (0.2%)
Cerebral Venous Thrombosis	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Cerebrovascular Accident	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Convulsion	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Dyskinesia	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Epilepsy	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Muscle Spasticity	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Paraesthesia	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Paraparesis	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Progressive Multiple Sclerosis	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Syncope	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Trigeminal Neuralgia	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Uhthoff's Phenomenon	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Psychiatric disorders
Hypomania	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Suicide Attempt	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Renal and urinary disorders
Bladder Disorder	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Bladder Dysfunction	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Reproductive system and breast disorders
Benign Prostatic Hyperplasia	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Erectile Dysfunction	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Metrorrhagia	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Ovarian Cyst Ruptured	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Respiratory, thoracic and mediastinal disorders
Lung Disorder	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Skin and subcutaneous tissue disorders
Decubitus Ulcer	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Surgical and medical procedures
Liposuction	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Stent Placement	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Stent Removal	1/707 (0.1%)		0/128 (0%)		1/835 (0.1%)
Other (Not Including Serious) Adverse Events
	Responder		Non-responder		All Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	314/707 (44.4%)		41/128 (32%)		355/835 (42.5%)
Gastrointestinal disorders
Nausea	60/707 (8.5%)		6/128 (4.7%)		66/835 (7.9%)
General disorders
Fatigue	31/707 (4.4%)		7/128 (5.5%)		38/835 (4.6%)
Infections and infestations
Urinary Tract Infection	58/707 (8.2%)		7/128 (5.5%)		65/835 (7.8%)
Nasopharyngitis	60/707 (8.5%)		1/128 (0.8%)		61/835 (7.3%)
Injury, poisoning and procedural complications
Fall	50/707 (7.1%)		5/128 (3.9%)		55/835 (6.6%)
Nervous system disorders
Headache	74/707 (10.5%)		6/128 (4.7%)		80/835 (9.6%)
Multiple Sclerosis Relapse	63/707 (8.9%)		2/128 (1.6%)		65/835 (7.8%)
Dizziness	35/707 (5%)		8/128 (6.3%)		43/835 (5.1%)
Psychiatric disorders
Insomnia	83/707 (11.7%)		12/128 (9.4%)		95/835 (11.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.

Results Point of Contact

Name/Title	Biogen Study Medical Director
Organization	Biogen
Phone
Email	clinicaltrials@biogen.com

Responsible Party:

Biogen

ClinicalTrials.gov Identifier:

NCT01480076

Other Study ID Numbers:

218MS403

First Posted:

Nov 28, 2011

Last Update Posted:

Mar 21, 2017

Last Verified:

Feb 1, 2017