Study of Fampridine-ER Tablets in Patients With Multiple Sclerosis

• Sponsor: Acorda Therapeutics (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01328379
• Collaborator: (none)
• Enrollment: 430
• Locations: 70
• Arms: 3
• Duration (Months): 16
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the safety and efficacy of a lower dose of dalfampridine extended release tablets compared to the currently approved dose in improving walking in Multiple Sclerosis (MS) patients.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: Dalfampridine-ER 5mg; Drug: Dalfampridine-ER 10mg; Other: Placebo	Phase 3

Detailed Description

The current study is designed as a prospective placebo-controlled trial to investigate the safety and efficacy of a lower dose of dalfampridine extended release tablets (5 mg twice daily) compared to the approved commercial dose of 10 mg twice daily in improving walking in MS patients during a four-week period of treatment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 430 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Safety and Efficacy of Two Doses of Oral Dalfampridine Extended Release Tablets (5 mg and 10 mg Twice Daily) in Patients With Multiple Sclerosis
• Study Start Date: Mar 1, 2011
• Actual Primary Completion Date: Apr 1, 2012
• Actual Study Completion Date: Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dalfampridine-ER 5mg 5mg, twice daily	Drug: Dalfampridine-ER 5mg; 5mg, twice daily; Other Names: Fampridine, Dalfampridine, Ampyra
Active Comparator: Dalfampridine-ER 10mg 10mg, twice daily	Drug: Dalfampridine-ER 10mg; 10mg, twice daily; Other Names: Fampridine, Dalfampridine, Ampyra
Placebo Comparator: Placebo placebo, twice daily	Other: Placebo; placebo, twice daily

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Walking Speed Near Maximum Plasma Concentration at Steady State (CmaxSS) of Placebo and Dalfampridine-ER (5mg and 10mg), Using the Timed 25 Foot Walk (T25FW). [Baseline Visit 1 (double-blind study day 1) and approximately 3-4 hours post dose at Visit 3 (end of double-blind week 4)]

   The T25FW test is a quantitative measure of ambulatory function that is widely used by MS specialists to assess the global impact of the disease and its progression on the patient's physical disability. A patient will stand with the toes of his/her shoes on the starting line (identified by a taped mark on the floor) and timing will begin when any part of the patient's foot crosses the tape. Timing will end when any part of the patient's foot crosses the finish line (identified by a taped mark on the floor). Time will be recorded in seconds and rounded to the nearest tenth of a second using a stopwatch provided for this study.

Secondary Outcome Measures

1. Change From Baseline in Walking Speed Near Minimum Plasma Concentration at Steady State (CminSS) of Placebo, Dalfampridine-ER (5mg and 10mg), Using the Timed 25 Foot Walk (T25FW). [Baseline Visit 1 (double-blind study day 1) and approximately 12 hours post dose at Visit 3 (end of double-blind week 4)]

   The T25FW test is a quantitative measure of ambulatory function that is widely used by MS specialists to assess the global impact of the disease and its progression on the patient's physical disability. A patient will stand with the toes of his/her shoes on the starting line (identified by a taped mark on the floor) and timing will begin when any part of the patient's foot crosses the tape. Timing will end when any part of the patient's foot crosses the finish line (identified by a taped mark on the floor). Time will be recorded in seconds and rounded to the nearest tenth of a second using a stopwatch provided for this study.

2. Change From Baseline in 12-item MS Walking Scale (MSWS-12) at Visit 3 [Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4)]

   The MSWS-12 is a multi-item rating scale that asks patients to rate limitations of their mobility due to MS during the preceding two weeks on a 5-point scale (from 1= not at all to 5=extremely). The scale assesses a range of activities of daily life that rely on walking, such as climbing stairs, moving around the home and walking distances outdoors. The MSWS-12 also addresses the quality of walking, with questions on the smoothness, speed, distance, effort, and mental concentration involved in walking, as well as the need for assistive devices. For each visit, the MSWS-12 score was calculated by summing the 12 components and transforming into a scale with a range of 0 to 100. MSWS-12 Score = 100 * [(Sum of Items 1-12) - 12]/48

3. Change From Baseline in MSWS-12 at Visit 2 [Visit 1 (Baseline) and Visit 2 (start of third week double-blind treatment period )]

   The MSWS-12 is a multi-item rating scale that asks patients to rate limitations of their mobility due to MS during the preceding two weeks on a 5-point scale (from 1= not at all to 5=extremely). The scale assesses a range of activities of daily life that rely on walking, such as climbing stairs, moving around the home and walking distances outdoors. The MSWS-12 also addresses the quality of walking, with questions on the smoothness, speed, distance, effort, and mental concentration involved in walking, as well as the need for assistive devices. For each visit, the MSWS-12 score was calculated by summing the 12 components and transforming into a scale with a range of 0 to 100. MSWS-12 Score = 100 * [(Sum of Items 1-12) - 12]/48

4. Change From Baseline in Six-Minute Walk Distance at Visit 2 [Visit 1 (Baseline) and Visit 2 (start of third week double-blind treatment period )]

   The Six-Minute Walk, a test of endurance, measures the distance that a patient can walk in a period of 6 minutes. Six-minute walk distance will be reported in feet.

5. Change From Baseline in EuroQol Group 5 Dimensions (EQ-5D) Scores at Visit 3. [Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4)]

   Patients completed a brief, generic health status questionnaire: The five specific dimensional scores value patients' health related to mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each question has 3 distinguishable choices that can be analyzed using a 3-point scale (i.e. 1 = no problem, 2=some problems and 3= extreme problems). A response of 1 indicates that the patient has no problem with the dimension tested and a response of 3 indicates that the patient has extreme problems with the dimension tested. For each visit, the average score of 5 dimensions was calculated by averaging the scores of 5 dimensions. EQ-5D final score ranges from 1-3.

6. Change From Baseline in EQ-5D Visual Analogue Self-rating (VAS) Score at Visit 3. [Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4)]

   The EQ-5D is a brief questionnaire that asks patients to rate general state of health. The VAS score rates the general state of health of a patient with 100 for the best imaginable health state and 0 for the worst imaginable health state.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient has clinically definite Multiple Sclerosis as defined by the MacDonald Criteria.

• Patient must be 18 to 70 years of age, inclusive (i.e. on or after their 18th birthday, up to the day before their 71st birthday at the Screening Visit).

• Patient who has previously taken Ampyra® or dalfampridine (fampridine or 4 aminopyridine; 4-AP) in any formulation (including compounded), must have withdrawn from the drug for at least one month prior to the Screening Visit.

• Patient must be mentally competent to understand and sign the Internal Review Board (IRB)-approved informed consent prior to the performance of any study-specific procedures.

• Patient is able to perform all the required study procedures.

• In the judgement of the Investigator, the patient has MS-related walking impairment but has sufficient ambulatory ability to be able to complete two trials of the Timed 25 Foot Walk (T25FW) at the screening Visit and every study visit thereafter, with the two trials completed within 5 minutes of one another and in accordance with the specific instructions provided by the National Multiple Sclerosis Society MS Functional Composite Manual.

• Patient who is female and of childbearing potential (see Exclusion Criterion 1 for definition) must have a negative urine pregnancy test at the Screening Visit.

Exclusion Criteria:

• Patient is a female of childbearing potential (i.e., has not had a hysterectomy or bilateral oophorectomy, or is not at least two years postmenopausal), engaged in active heterosexual relations and is not using one of the following birth control methods: tubal ligation, implantable contraception device, oral, patch or injectable contraceptive, double barrier method, or sexual activity restricted to vasectomized partner.

• Patient is pregnant or breastfeeding.

• Patient has any history of seizures.

• Patient has moderate or severe renal impairment as defined by a calculated creatinine clearance of ≤ 50 mL/minute.

• Patient has active urinary tract infection (UTI) at Screening or within the 4 weeks before Screening.

• Patient has had an onset (as assessed by the treating physician) of an MS exacerbation within 60 days prior to the Screening Visit.

• Patient has started on a concomitant prescription medication regimen within the last three weeks, and/or their concomitant medication regimen is expected to change during the course of the study.

• Patient has received cyclophosphamide (Cytoxan) or mitoxantrone (Novantrone) for MS treatment within six months prior to the Screening Visit.

• Patient has started a treatment regimen of Betaseron, Avonex, Copaxone, Rebif, Tysabri, Extavia or Gilenya™ within 90 days prior to the Screening Visit or has had any change in the dosing regimen of these drugs within 30 days prior to the Screening Visit.

• Patient has received corticosteroids (other than topical preparations) within 30 days prior to the Screening Visit and/or is expected to receive regularly scheduled corticosteroid treatment during the course of the study.

• Patient has been administered botulinum toxin in the lower extremities within six months prior to the Screening Visit and/or is expected to receive botulinum toxin in the lower extremities during the course of the study.

• Patient has a known allergy to pyridine-containing substances or any of the inactive ingredients of the dalfampridine tablet (colloidal silicon dioxide, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, and titanium dioxide).

• Patient has a history of drug or alcohol abuse within the past year.

• Patient has clinically significant abnormal laboratory values.

• Patient has angina, uncontrolled hypertension, clinically significant cardiac arrhythmias, or any other clinically significant cardiovascular abnormality.

• Patient has any medical condition (including psychiatric disease)that would interfere with the interpretation of the study results or the conduct of the study.

• Patient has participated in an investigational trial 30 days prior to Screening Visit or plans to enroll in another investigational trial at any time during this study. Non-drug (i.e. observational, registry) and non- medical device trials are allowed.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	North Central Neurology Associates, PC	Cullman	Alabama	United States
2	Phoenix Neurological Associates, Ltd	Phoenix	Arizona	United States
3	Arizona Neurological Institute	Sun City	Arizona	United States
4	Clinical Research Advantage Inc.	Tempe	Arizona	United States
5	Sutter East Bay Physicians Medical Foundation	Berkeley	California	United States
6	Neuro-Pain Medical Center, Inc.	Fresno	California	United States
7	Loma Linda University Medical Center	Loma Linda	California	United States
8	Collaborative NeuroScience Network, Inc.	Long Beach	California	United States
9	University of California Davis Medical Center	Sacramento	California	United States
10	Mount Sinai Rehabilitation Hospital	Hartford	Connecticut	United States
11	Georgetown University Hospital	Washington	District of Columbia	United States
12	Neurology Associates, PA	Maitland	Florida	United States
13	University of Miami School of Medicine, Dept. of Neurology	Miami	Florida	United States
14	Neurological Associates	Pompano Beach	Florida	United States
15	Neurologique Foundation, Inc.	Ponte Vedra	Florida	United States
16	Suncoast Neuroscience Associates, Inc.	Saint Petersburg	Florida	United States
17	Negroski, Sutherland and Hanes Neurology	Sarasota	Florida	United States
18	Tallahassee Neurological Clinic, PA	Tallahassee	Florida	United States
19	Axiom Clinical Research of Florida	Tampa	Florida	United States
20	The Multiple Sclerosis Center of Vero Beach	Vero Beach	Florida	United States
21	Sheperd Center, Inc.	Atlanta	Georgia	United States
22	Northwestern University	Chicago	Illinois	United States
23	Consultants in Neurology Ltd.	Northbrook	Illinois	United States
24	Indiana University School of Medicine	Indianapolis	Indiana	United States
25	Josephson Wallack Munshower Neurology, PC	Indianapolis	Indiana	United States
26	Methodist Plaza Specialty	Des Moines	Iowa	United States
27	Ruan Neurology Clinic and Research Center	Des Moines	Iowa	United States
28	The University of Kansas Medical Center	Kansas City	Kansas	United States
29	Associates in Neurology, PSC	Lexington	Kentucky	United States
30	University of Maryland, Maryland Center for Multiple Sclerosis	Baltimore	Maryland	United States
31	Lahey Clinic	Lexington	Massachusetts	United States
32	Springfield Neurology Associates, LLC	Springfield	Massachusetts	United States
33	Wayne State University	Detroit	Michigan	United States
34	Advanced Neurology Specialists	Great Falls	Montana	United States
35	Veterans Administration Sierra Neveda Health Care System	Reno	Nevada	United States
36	Upstate Clinical Research, LLC	Albany	New York	United States
37	NYU Langone Medical Center MS Comprehensive Care Center	New York	New York	United States
38	Comprehensive Multiple Sclerosis Care Center at South Shore Neurologic Associates	Patchogue	New York	United States
39	Island Neurological Associates, PC	Plainview	New York	United States
40	University of Rochester Medical Center	Rochester	New York	United States
41	PMG Research of Charlotte	Charlotte	North Carolina	United States
42	The Neurological Institute, PA	Charlotte	North Carolina	United States
43	PMG Research of Hickory, LLC	Hickory	North Carolina	United States
44	Raleigh Neurology Associates	Raleigh	North Carolina	United States
45	PMG Research of Winston-Salem	Winston-Salem	North Carolina	United States
46	Altru Health System Clinic	Grand Forks	North Dakota	United States
47	Northern Ohio Neuroscience, LLC	Bellevue	Ohio	United States
48	Cleveland Clinic Foundation	Cleveland	Ohio	United States
49	Neurological Research Institute	Columbus	Ohio	United States
50	Ohio State University, Columbus	Columbus	Ohio	United States
51	Neurology Specialists, Inc.	Dayton	Ohio	United States
52	OMRF Multiple Sclerosis Center of Excellence	Oklahoma City	Oklahoma	United States
53	Oregon Health and Science University	Portland	Oregon	United States
54	Providence Multiple Sclerosis Center	Portland	Oregon	United States
55	The Pennsylvania State University, Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States
56	Hospital of the University of Pennsylvania	Philadelphia	Pennsylvania	United States
57	Temple University School of Medicine	Philadelphia	Pennsylvania	United States
58	The Neurology Foundation, Inc.	Providence	Rhode Island	United States
59	Wesley Neurology Clinic, PC	Cordova	Tennessee	United States
60	Advanced Neurosciences Institute	Franklin	Tennessee	United States
61	Sibyl E. Wray, MD, Neurology, PC	Knoxville	Tennessee	United States
62	Texas Neurology, PA	Dallas	Texas	United States
63	Kelsey-Seybold Clinic	Houston	Texas	United States
64	Maxine Mesinger Multiple Sclerosis Clinic; Baylor College of Medicine	Houston	Texas	United States
65	Fletcher Allen Health Care	Burlington	Vermont	United States
66	Hampton Roads Neurology	Newport News	Virginia	United States
67	Neurological Associates	Richmond	Virginia	United States
68	Virginia Commonwealth University	Richmond	Virginia	United States
69	Swedish Neuroscience Institute	Seattle	Washington	United States
70	Aurora Saint Luke's Medical Center	Milwaukee	Wisconsin	United States

Sponsors and Collaborators

• Acorda Therapeutics

Investigators

• Study Director: Andrew R. Blight, PhD, Acorda Therapeutics
• Principal Investigator: Mark Agius, MD, University of California, Davis
• Principal Investigator: Angela Applebee, MD, University of Vermont Medical Center
• Principal Investigator: S. A Azizi, MD, PhD, Temple University Hospital
• Principal Investigator: Francois Bethoux, MD, The Cleveland Clinic
• Principal Investigator: Christopher Bever, Jr., MD, University of Maryland, Maryland Center for Multiple Sclerosis
• Principal Investigator: Eric Borresen, MD, Metrolina Medical Research
• Principal Investigator: Aaron Boster, MD, Ohio State University, Columbus
• Principal Investigator: Ann Camac, MD, Lahey Clinic
• Principal Investigator: Mark Cascione, MD, Axiom Clinical Research of Florida
• Principal Investigator: Jane Chan, MD, US Department of Veterans Affairs
• Principal Investigator: Warren Chumley, MD, Associates in Neurology, PSC
• Principal Investigator: Joanna Cooper, MD, Alta Bates Summit Medical Center
• Principal Investigator: Joy Derwenskus, DO, Northwestern University
• Principal Investigator: Adam DiDio, MD, Suncoast Neuroscience Associates, Inc.
• Principal Investigator: Dennis Dietrich, MD, Advanced Neurology Specialists
• Principal Investigator: Geoffery Eubank, MD, Neurological Research Institute
• Principal Investigator: Steven Freedman, MD, Raleigh Neurology Associates
• Principal Investigator: Daniel Giang, MD, Loma Linda University Medical Center
• Principal Investigator: Lawrence Goldstick, MD, Neurology Specialists, Inc.
• Principal Investigator: Andrew Goodman, MD, University of Rochester
• Principal Investigator: Mark Gudesblatt, MD, Comprehensive Multiple Sclerosis Care Center at South Shore Neurologic Associates, P.C.
• Principal Investigator: Barry Hendin, MD, Phoenix Neurological Associates, LTD
• Principal Investigator: Craig Herrman, MD, Josephson Wallack Munshower Neurology, PC
• Principal Investigator: William Honeycutt, MD, Neurology Associates, PA
• Principal Investigator: Bruce Hughes, MD, Ruan Neurology Clinical Research Center
• Principal Investigator: Samuel Hunter, MD, PhD, Advanced Neurosciences Institute
• Principal Investigator: George Hutton, MD, Maxine Mesinger Multiple Sclerosis Clinic; Baylor College of Medicine
• Principal Investigator: Dina Jacobs, MD, University of Pennsylvania
• Principal Investigator: Todd Janus, MD, PhD, Iowa Health Des Moines
• Principal Investigator: Omar Khan, MD, Wayne State University
• Principal Investigator: Bhupendra Khatri, MD, Aurora Saint Luke's Medical Center
• Principal Investigator: Kiren Kresa-Reahl, MD, Charleston Area Medical Center Health Education and Research Institute, Inc.
• Principal Investigator: Christopher LaGanke, MD, North Central Neurology Associates, PC
• Principal Investigator: Sharon Lynch, MD, The University of Kansas Medical Center
• Principal Investigator: Michele Mass, MD, Oregon Health and Science University
• Principal Investigator: David Mattson, MD, PhD, Indiana University
• Principal Investigator: Angeli Mayadev, MD, Swedish Neuroscience Institute
• Principal Investigator: Donald Negroski, MD, Negroski, Stein, Sutherland and Hanes Neurology
• Principal Investigator: Stephen Newman, MD, Island Neurological Associates, PC
• Principal Investigator: Gabriel Pardo, MD, Mercy Multiple Sclerosis Center of Oklahoma Mercy Neuroscience Institute
• Principal Investigator: C. Fish Greenfield, MD, Texas Neurology, PA
• Principal Investigator: Rekha Pillai, MD, Neurology Clinic, PC
• Principal Investigator: T. Hemanth Rao, MD, The Neurological Institute, PA
• Principal Investigator: Syed Rizvi, MD, Rhode Island Hospital
• Principal Investigator: Matthew Roller, MD, Altru Health System Research Center
• Principal Investigator: Michael Rossen, MD, PhD, Springfield Neurology Associates, LLC
• Principal Investigator: Alan Schulman, MD, Neurological Associates
• Principal Investigator: James S Shafer, MD, The Multiple Sclerosis Center of Vero Beach
• Principal Investigator: Jatin Shah, MD, Arizona Neurological Institute
• Principal Investigator: William Sheremata, MD, University of Miami School of Medicine, Dept. of Neurology
• Principal Investigator: Brian Steingo, MD, Neurological Associates
• Principal Investigator: James Storey, Jr, MD, Upstate Clinical Research, LLC
• Principal Investigator: Ben Thrower, MD, Shepherd Center, Inc.
• Principal Investigator: Carlo Tornatore, MD, Georgetown University Hospital
• Principal Investigator: K A Lloyd, MD, Hampton Roads Neurology
• Principal Investigator: Anthony Turel, Jr, MD, The Pennsylvania State University, Milton S. Hershey Medical Center
• Principal Investigator: Sibyl E Wray, MD, Sibyl E. Wray, MD, Neurology, PC
• Principal Investigator: Daniel Wynn, MD, Consultants in Neurology Ltd.
• Principal Investigator: Robert Yapundich, MD, Unifour Medical Research, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Acorda Therapeutics
• ClinicalTrials.gov Identifier: NCT01328379
• Other Study ID Numbers: DER-401
• First Posted: Apr 4, 2011
• Last Update Posted: Sep 5, 2013
• Last Verified: Sep 1, 2013

• Additional relevant MeSH terms: Multiple Sclerosis; Sclerosis; 4-Aminopyridine

Study Results

Participant Flow

Recruitment Details	Patients were to be enrolled at a minimum of 60 investigational centers in the United States until a minimum of 405 patients had been randomized.

Arm/Group Title	Placebo	Dalfampridine-ER 5mg	Dalfampridine-ER 10mg
Arm/Group Description	placebo, twice daily	5mg, twice daily Dalfampridine-ER 5mg: 5mg, twice daily	10mg, twice daily Dalfampridine-ER 10mg: 10mg, twice daily
Period Title: Overall Study
STARTED	143	144	143
COMPLETED	142	144	143
NOT COMPLETED	1	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Dalfampridine-ER 5mg	Dalfampridine-ER 10mg	Total
Arm/Group Description	placebo, twice daily	5mg, twice daily Dalfampridine-ER 5mg: 5mg, twice daily	10mg, twice daily Dalfampridine-ER 10mg: 10mg, twice daily	Total of all reporting groups
Overall Participants	142	144	143	429
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.2 (0.83)	52.2 (0.77)	53.4 (0.79)	52.6 (0.46)
Sex: Female, Male (Count of Participants)
Female	100 70.4%	102 70.8%	98 68.5%	300 69.9%
Male	42 29.6%	42 29.2%	45 31.5%	129 30.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	10 7%	7 4.9%	3 2.1%	20 4.7%
Not Hispanic or Latino	132 93%	137 95.1%	140 97.9%	409 95.3%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Walking Speed Near Maximum Plasma Concentration at Steady State (CmaxSS) of Placebo and Dalfampridine-ER (5mg and 10mg), Using the Timed 25 Foot Walk (T25FW).
Description	The T25FW test is a quantitative measure of ambulatory function that is widely used by MS specialists to assess the global impact of the disease and its progression on the patient's physical disability. A patient will stand with the toes of his/her shoes on the starting line (identified by a taped mark on the floor) and timing will begin when any part of the patient's foot crosses the tape. Timing will end when any part of the patient's foot crosses the finish line (identified by a taped mark on the floor). Time will be recorded in seconds and rounded to the nearest tenth of a second using a stopwatch provided for this study.
Time Frame	Baseline Visit 1 (double-blind study day 1) and approximately 3-4 hours post dose at Visit 3 (end of double-blind week 4)

Outcome Measure Data

Analysis Population Description

Full Analysis Population (FAP): All randomized patients who took at least one dose of double-blind investigational medication and who have a baseline Timed 25 Foot Walk (T25FW) assessment and at least one post-baseline T25FW assessment.

Arm/Group Title	Placebo	Dalfampridine-ER 5mg	Dalfampridine-ER 10mg
Arm/Group Description	placebo, twice daily	5mg, twice daily Dalfampridine-ER 5mg: 5mg, twice daily	10mg, twice daily Dalfampridine-ER 10mg: 10mg, twice daily
Measure Participants	136	143	136
Mean (Standard Error) [feet per second]	0.363 (0.0511)	0.423 (0.0470)	0.478 (0.0569)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dalfampridine-ER 5mg
	Comments	dalfampridine-ER 5mg twice daily vs. placebo twice daily: Change from baseline in walking speed at Approximately CmaxSS at Visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.457
	Comments	To demonstrate study sensitivity with respect to efficacy and maintain an overall alpha level ≤ 0.05, a stepwise procedure was performed.
	Method	ANOVA
	Comments	ANOVA Model: Change from Baseline in Walking Speed - dependent variable and Baseline Walking Speed and Treatment - independent variables
Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	0.054
	Confidence Interval	(2-Sided) 95%; -0.088 to 0.196
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0724
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dalfampridine-ER 10mg
	Comments	dalfampridine-ER 10mg twice daily vs. placebo twice daily: Change from baseline in walking speed at Approximately CmaxSS at Visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.107
	Comments
	Method	ANOVA
	Comments	ANOVA Model: Change from Baseline in Walking Speed - dependent variable and Baseline Walking Speed and Treatment - independent variables
Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	0.118
	Confidence Interval	(2-Sided) 95%; -0.026 to 0.262
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0732
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dalfampridine-ER 5mg, Dalfampridine-ER 10mg
	Comments	dalfampridine-ER 5mg twice daily vs. dalfampridine-ER 10mg twice daily: Change from baseline in walking speed at Approximately CmaxSS at Visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.375
	Comments
	Method	ANOVA
	Comments	ANOVA Model: Change from Baseline in Walking Speed - dependent variable and Baseline Walking Speed and Treatment - independent variables
Method of Estimation	Estimation Parameter	least squares mean
	Estimated Value	0.064
	Confidence Interval	(2-Sided) 95%; -0.078 to 0.207
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0724
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in Walking Speed Near Minimum Plasma Concentration at Steady State (CminSS) of Placebo, Dalfampridine-ER (5mg and 10mg), Using the Timed 25 Foot Walk (T25FW).
Description	The T25FW test is a quantitative measure of ambulatory function that is widely used by MS specialists to assess the global impact of the disease and its progression on the patient's physical disability. A patient will stand with the toes of his/her shoes on the starting line (identified by a taped mark on the floor) and timing will begin when any part of the patient's foot crosses the tape. Timing will end when any part of the patient's foot crosses the finish line (identified by a taped mark on the floor). Time will be recorded in seconds and rounded to the nearest tenth of a second using a stopwatch provided for this study.
Time Frame	Baseline Visit 1 (double-blind study day 1) and approximately 12 hours post dose at Visit 3 (end of double-blind week 4)

Outcome Measure Data

Analysis Population Description

Full Analysis Population

Arm/Group Title	Placebo	Dalfampridine-ER 5mg	Dalfampridine-ER 10mg
Arm/Group Description	placebo, twice daily	5mg, twice daily Dalfampridine-ER 5mg: 5mg, twice daily	10mg, twice daily Dalfampridine-ER 10mg: 10mg, twice daily
Measure Participants	136	143	136
Mean (Standard Error) [feet per second]	0.301 (0.0496)	0.296 (0.0429)	0.391 (0.0513)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dalfampridine-ER 5mg
	Comments	dalfampridine-ER 5mg twice daily vs. placebo twice daily: Change from baseline in walking speed at Approximately CminSS at Visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.832
	Comments	To demonstrate study sensitivity with respect to efficacy and maintain an overall alpha level ≤ 0.05, a stepwise procedure was performed.
	Method	ANOVA
	Comments	ANOVA Model: Change from Baseline in Walking Speed - dependent variable and Baseline Walking Speed and Treatment - independent variables
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-0.014
	Confidence Interval	(2-Sided) 95%; -0.145 to 0.117
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0666
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dalfampridine-ER 10mg
	Comments	dalfampridine-ER 10mg twice daily vs. placebo twice daily: Change from baseline in walking speed at Approximately CminSS at Visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.167
	Comments
	Method	ANOVA
	Comments	ANOVA Model: Change from Baseline in Walking Speed - dependent variable and Baseline Walking Speed and Treatment - independent variables
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	0.093
	Confidence Interval	(2-Sided) 95%; -0.039 to 0.226
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0674
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dalfampridine-ER 5mg, Dalfampridine-ER 10mg
	Comments	dalfampridine-ER 5mg twice daily vs. dalfampridine-ER 10mg twice daily: Change from baseline in walking speed at Approximately CminSS at Visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.108
	Comments
	Method	ANOVA
	Comments	ANOVA Model: Change from Baseline in Walking Speed - dependent variable and Baseline Walking Speed and Treatment - independent variables
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	0.107
	Confidence Interval	(2-Sided) 95%; -0.024 to 0.238
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0666
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in 12-item MS Walking Scale (MSWS-12) at Visit 3
Description	The MSWS-12 is a multi-item rating scale that asks patients to rate limitations of their mobility due to MS during the preceding two weeks on a 5-point scale (from 1= not at all to 5=extremely). The scale assesses a range of activities of daily life that rely on walking, such as climbing stairs, moving around the home and walking distances outdoors. The MSWS-12 also addresses the quality of walking, with questions on the smoothness, speed, distance, effort, and mental concentration involved in walking, as well as the need for assistive devices. For each visit, the MSWS-12 score was calculated by summing the 12 components and transforming into a scale with a range of 0 to 100. MSWS-12 Score = 100 * [(Sum of Items 1-12) - 12]/48
Time Frame	Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4)

Outcome Measure Data

Analysis Population Description

Full Analysis Population

Arm/Group Title	Placebo	Dalfampridine-ER 5mg	Dalfampridine-ER 10mg
Arm/Group Description	placebo, twice daily	5mg, twice daily Dalfampridine-ER 5mg: 5mg, twice daily	10mg, twice daily Dalfampridine-ER 10mg: 10mg, twice daily
Measure Participants	136	143	136
Mean (Standard Error) [scores on a scale]	-8.35 (1.774)	-9.73 (1.741)	-11.10 (1.818)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dalfampridine-ER 5mg
	Comments	dalfampridine-ER 5mg twice daily vs. placebo twice daily: Change from baseline in MSWS-12 at visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.866
	Comments
	Method	ANOVA
	Comments	ANOVA model with change from baseline in MSWS-12 Score as the dependent variable and baseline MSWS-12 Score and treatment as the independent variables
Method of Estimation	Estimation Parameter	Lease Squares Mean
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -5.05 to 4.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.367
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dalfampridine-ER 10mg
	Comments	dalfampridine-ER 10mg twice daily vs. placebo twice daily: Change from baseline in MSWS-12 at visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.286
	Comments
	Method	ANOVA
	Comments	ANOVA model with change from baseline in MSWS-12 Score as the dependent variable and baseline MSWS-12 Score and treatment as the independent variables
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-2.56
	Confidence Interval	(2-Sided) 95%; -7.26 to 2.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.393
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dalfampridine-ER 5mg, Dalfampridine-ER 10mg
	Comments	dalfampridine-ER 5mg twice daily vs. dalfampridine-ER 10mg twice daily: Change from baseline in MSWS-12 at visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.362
	Comments
	Method	ANOVA
	Comments	ANOVA model with change from baseline in MSWS-12 Score as the dependent variable and baseline MSWS-12 Score and treatment as the independent variables
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-2.16
	Confidence Interval	(2-Sided) 95%; -6.81 to 2.49
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.366
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in MSWS-12 at Visit 2
Description	The MSWS-12 is a multi-item rating scale that asks patients to rate limitations of their mobility due to MS during the preceding two weeks on a 5-point scale (from 1= not at all to 5=extremely). The scale assesses a range of activities of daily life that rely on walking, such as climbing stairs, moving around the home and walking distances outdoors. The MSWS-12 also addresses the quality of walking, with questions on the smoothness, speed, distance, effort, and mental concentration involved in walking, as well as the need for assistive devices. For each visit, the MSWS-12 score was calculated by summing the 12 components and transforming into a scale with a range of 0 to 100. MSWS-12 Score = 100 * [(Sum of Items 1-12) - 12]/48
Time Frame	Visit 1 (Baseline) and Visit 2 (start of third week double-blind treatment period )

Outcome Measure Data

Analysis Population Description

Full Analysis Population

Arm/Group Title	Placebo	Dalfampridine-ER 5mg	Dalfampridine-ER 10mg
Arm/Group Description	placebo, twice daily	5mg, twice daily Dalfampridine-ER 5mg: 5mg, twice daily	10mg, twice daily Dalfampridine-ER 10mg: 10mg, twice daily
Measure Participants	136	142	136
Mean (Standard Error) [scores on a scale]	-9.48 (1.713)	-9.54 (1.526)	-10.04 (1.817)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dalfampridine-ER 5mg
	Comments	dalfampridine-ER 5mg twice daily vs. placebo twice daily: Change from baseline in MSWS-12 at visit 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.708
	Comments
	Method	ANOVA
	Comments	ANOVA model with change from baseline in MSWS-12 Score as the dependent variable and baseline MSWS-12 Score and treatment as the independent variables
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; -3.56 to 5.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.237
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dalfampridine-ER 10mg
	Comments	dalfampridine-ER 10mg twice daily vs. placebo twice daily: Change from baseline in MSWS-12 at visit 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.868
	Comments
	Method	ANOVA
	Comments	ANOVA model with change from baseline in MSWS-12 Score as the dependent variable and baseline MSWS-12 Score and treatment as the independent variables
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -4.81 to 4.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.258
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dalfampridine-ER 5mg, Dalfampridine-ER 10mg
	Comments	dalfampridine-ER 5mg twice daily vs. dalfampridine-ER 10mg twice daily: Change from baseline in MSWS-12 at visit 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.588
	Comments
	Method	ANOVA
	Comments	ANOVA model with change from baseline in MSWS-12 Score as the dependent variable and baseline MSWS-12 Score and treatment as the independent variables
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-1.21
	Confidence Interval	(2-Sided) 95%; -5.61 to 3.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.236
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Six-Minute Walk Distance at Visit 2
Description	The Six-Minute Walk, a test of endurance, measures the distance that a patient can walk in a period of 6 minutes. Six-minute walk distance will be reported in feet.
Time Frame	Visit 1 (Baseline) and Visit 2 (start of third week double-blind treatment period )

Outcome Measure Data

Analysis Population Description

Full Analysis Population

Arm/Group Title	Placebo	Dalfampridine-ER 5mg	Dalfampridine-ER 10mg
Arm/Group Description	placebo, twice daily	5mg, twice daily Dalfampridine-ER 5mg: 5mg, twice daily	10mg, twice daily Dalfampridine-ER 10mg: 10mg, twice daily
Measure Participants	49	53	51
Mean (Standard Error) [Feet]	41.7 (23.36)	76.8 (27.31)	128.6 (21.66)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dalfampridine-ER 5mg
	Comments	dalfampridine-ER 5mg twice daily vs. placebo twice daily: Change from baseline in Six-Minute Walk Distance at visit 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.308
	Comments
	Method	ANOVA
	Comments	Change from Baseline in Six-Minute Walk Distance as dependent variable and Baseline Six-Minute Walk Distance and Treatment as independent variables.
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	35.4
	Confidence Interval	(2-Sided) 95%; -33.0 to 103.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 34.57
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dalfampridine-ER 10mg
	Comments	dalfampridine-ER 10mg twice daily vs. placebo twice daily: Change from baseline in Six-Minute Walk Distance at visit 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	ANOVA
	Comments	Change from Baseline in Six-Minute Walk Distance as dependent variable and Baseline Six-Minute Walk Distance and Treatment as independent variables.
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	87.1
	Confidence Interval	(2-Sided) 95%; 18.2 to 156.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 34.90
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dalfampridine-ER 5mg, Dalfampridine-ER 10mg
	Comments	dalfampridine-ER 5mg twice daily vs. dalfampridine-ER 10mg twice daily: Change from baseline in Six-Minute Walk Distance at visit 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.133
	Comments
	Method	ANOVA
	Comments	Change from Baseline in Six-Minute Walk Distance as dependent variable and Baseline Six-Minute Walk Distance and Treatment as independent variables.
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	51.7
	Confidence Interval	(2-Sided) 95%; -15.9 to 119.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 34.21
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in EuroQol Group 5 Dimensions (EQ-5D) Scores at Visit 3.
Description	Patients completed a brief, generic health status questionnaire: The five specific dimensional scores value patients' health related to mobility, self-care, usual activities, pain and discomfort, and anxiety and depression. Each question has 3 distinguishable choices that can be analyzed using a 3-point scale (i.e. 1 = no problem, 2=some problems and 3= extreme problems). A response of 1 indicates that the patient has no problem with the dimension tested and a response of 3 indicates that the patient has extreme problems with the dimension tested. For each visit, the average score of 5 dimensions was calculated by averaging the scores of 5 dimensions. EQ-5D final score ranges from 1-3.
Time Frame	Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4)

Outcome Measure Data

Analysis Population Description

Full Analysis Population

Arm/Group Title	Placebo	Dalfampridine-ER 5mg	Dalfampridine-ER 10mg
Arm/Group Description	placebo, twice daily	5mg, twice daily Dalfampridine-ER 5mg: 5mg, twice daily	10mg, twice daily Dalfampridine-ER 10mg: 10mg, twice daily
Measure Participants	132	139	126
Mean (Standard Error) [units on a scale]	-0.07 (0.023)	-0.05 (0.020)	-0.07 (0.024)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dalfampridine-ER 5mg
	Comments	dalfampridine-ER 5mg twice daily vs. placebo twice daily: Change from baseline in Average EQ-5D score at Visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.320
	Comments
	Method	ANOVA
	Comments	ANOVA model with change from baseline score as the dependant variable and baseline score and treatment as the independent variables.
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.0 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.03
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dalfampridine-ER 10mg
	Comments	dalfampridine-ER 10mg twice daily vs. placebo twice daily: Change from baseline in Average EQ-5D score at Visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.734
	Comments
	Method	ANOVA
	Comments	ANOVA model with change from baseline score as the dependant variable and baseline score and treatment as the independent variables.
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95%; -0.1 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.03
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dalfampridine-ER 5mg, Dalfampridine-ER 10mg
	Comments	dalfampridine-ER 5mg twice daily vs. dalfampridine-ER 10mg twice daily: Change from baseline in Average EQ-5D score at Visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.185
	Comments
	Method	ANOVA
	Comments	ANOVA model with change from baseline score as the dependant variable and baseline score and treatment as the independent variables.
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95%; -0.1 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.03
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in EQ-5D Visual Analogue Self-rating (VAS) Score at Visit 3.
Description	The EQ-5D is a brief questionnaire that asks patients to rate general state of health. The VAS score rates the general state of health of a patient with 100 for the best imaginable health state and 0 for the worst imaginable health state.
Time Frame	Baseline Visit 1 (double-blind study day 1) and Visit 3 (end of double-blind week 4)

Outcome Measure Data

Analysis Population Description

Full Analysis Population. The number of participants analyzed corresponds with number of subjects who completed the questionnaire in each treatment group.

Arm/Group Title	Placebo	Dalfampridine-ER 5mg	Dalfampridine-ER 10mg
Arm/Group Description	placebo, twice daily	5mg, twice daily Dalfampridine-ER 5mg: 5mg, twice daily	10mg, twice daily Dalfampridine-ER 10mg: 10mg, twice daily
Measure Participants	131	139	127
Mean (Standard Error) [units on a scale]	7.0 (1.43)	2.6 (1.53)	4.2 (1.48)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dalfampridine-ER 5mg
	Comments	dalfampridine-ER 5mg twice daily vs. placebo twice daily: Change from baseline in EQ-5D VAS score at Visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.055
	Comments
	Method	ANOVA
	Comments	ANOVA model with change from baseline score as the dependant variable and baseline score and treatment as the independent variables.
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-3.4
	Confidence Interval	(2-Sided) 95%; -7.0 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.79
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Dalfampridine-ER 10mg
	Comments	dalfampridine-ER 10mg twice daily vs. placebo twice daily: Change from baseline in EQ-5D VAS score at Visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.530
	Comments
	Method	ANOVA
	Comments	ANOVA model with change from baseline score as the dependant variable and baseline score and treatment as the independent variables.
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -4.7 to 2.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.83
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Dalfampridine-ER 5mg, Dalfampridine-ER 10mg
	Comments	dalfampridine-ER 5mg twice daily vs. dalfampridine-ER 10mg twice daily: Change from baseline in EQ-5D VAS score at Visit 3
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.203
	Comments
	Method	ANOVA
	Comments	ANOVA model with change from baseline score as the dependant variable and baseline score and treatment as the independent variables.
Method of Estimation	Estimation Parameter	Least Squares Mean
	Estimated Value	2.3
	Confidence Interval	(2-Sided) 95%; -1.2 to 5.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.80
	Estimation Comments

Adverse Events

Time Frame	On or after start of double-blind treatment through 14 days after the last dose for non-serious events, or up to 30 days after the last dose for serious adverse events (SAEs).
Adverse Event Reporting Description	Adverse events are treatment-emergent adverse events (TEAEs) that had a date of onset or worsening, on or after start of double-blind treatment. Number of participants exposed to study medication in the Dalfampridine-ER 10mg group (142) is 1 less than total # completed. 1 patient was randomized to Dalfampridine-ER 10mg but actually received placebo
Arm/Group Title	Placebo		Dalfampridine-ER 5mg		Dalfampridine-ER 10mg
Arm/Group Description	placebo, twice daily		5mg, twice daily Dalfampridine-ER 5mg: 5mg, twice daily		10mg, twice daily Dalfampridine-ER 10mg: 10mg, twice daily
All Cause Mortality
	Placebo		Dalfampridine-ER 5mg		Dalfampridine-ER 10mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Dalfampridine-ER 5mg		Dalfampridine-ER 10mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/143 (0%)		2/144 (1.4%)		2/142 (1.4%)
Ear and labyrinth disorders
Vertigo	0/143 (0%)	0	0/144 (0%)	0	1/142 (0.7%)	1
Infections and infestations
Breast abscess	0/143 (0%)	0	1/144 (0.7%)	1	0/142 (0%)	0
Breast cellulitis	0/143 (0%)	0	1/144 (0.7%)	1	0/142 (0%)	0
Urosepsis	0/143 (0%)	0	1/144 (0.7%)	1	0/142 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian adenoma	0/143 (0%)	0	0/144 (0%)	0	1/142 (0.7%)	1
Nervous system disorders
Loss of consciousness	0/143 (0%)	0	0/144 (0%)	0	1/142 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Placebo		Dalfampridine-ER 5mg		Dalfampridine-ER 10mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	77/143 (53.8%)		80/144 (55.6%)		84/142 (59.2%)
Gastrointestinal disorders
Diarrhoea	6/143 (4.2%)	8	3/144 (2.1%)	3	3/142 (2.1%)	3
Dyspepsia	1/143 (0.7%)	1	6/144 (4.2%)	7	1/142 (0.7%)	1
Nausea	5/143 (3.5%)	5	11/144 (7.6%)	12	11/142 (7.7%)	12
General disorders
Fatigue	3/143 (2.1%)	3	4/144 (2.8%)	5	4/142 (2.8%)	4
Infections and infestations
Nasopharyngitis	3/143 (2.1%)	3	2/144 (1.4%)	2	6/142 (4.2%)	6
Upper respiratory tract infection	1/143 (0.7%)	2	5/144 (3.5%)	5	3/142 (2.1%)	3
Urinary tract infection	8/143 (5.6%)	9	9/144 (6.3%)	9	14/142 (9.9%)	14
Injury, poisoning and procedural complications
Fall	7/143 (4.9%)	9	10/144 (6.9%)	13	3/142 (2.1%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	2/143 (1.4%)	3	5/144 (3.5%)	5	3/142 (2.1%)	4
Back pain	4/143 (2.8%)	4	5/144 (3.5%)	5	6/142 (4.2%)	6
Muscle spasms	4/143 (2.8%)	4	6/144 (4.2%)	6	3/142 (2.1%)	3
Pain in extremity	4/143 (2.8%)	4	4/144 (2.8%)	6	6/142 (4.2%)	6
Nervous system disorders
Balance disorder	6/143 (4.2%)	7	3/144 (2.1%)	3	2/142 (1.4%)	2
Dizziness	3/143 (2.1%)	3	7/144 (4.9%)	7	15/142 (10.6%)	17
Headache	16/143 (11.2%)	17	13/144 (9%)	15	18/142 (12.7%)	18
Paraesthesia	4/143 (2.8%)	4	2/144 (1.4%)	2	7/142 (4.9%)	12
Psychiatric disorders
Insomnia	6/143 (4.2%)	6	7/144 (4.9%)	7	11/142 (7.7%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor (Acorda) has right to review and comment on proposed publications within a specified time frame, up to 60 days; multi-center trials require joint publication unless specifically permitted otherwise.