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ENDORSE: BG00012 Monotherapy Safety and Efficacy Extension Study in Multiple Sclerosis (MS)

Sponsor
Biogen (Industry)
Overall Status
Completed
CT.gov ID
NCT00835770
Collaborator
(none)
1,736
Enrollment
246
Locations
2
Arms
129.1
Actual Duration (Months)
7.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the long-term safety profile of BG00012 (dimethyl fumarate). Secondary objectives of this study are to evaluate the long-term efficacy of BG00012 using clinical endpoints and disability progression, to evaluate further the long-term effects of BG00012 on multiple sclerosis (MS) brain lesions on magnetic resonance imaging (MRI) scans in participants who had MRI scans as part of Studies 109MS301 (NCT00420212) and 109MS302 (NCT00451451) and to evaluate the long-term effects of BG00012 on health economics assessments and the visual function test.

Condition or Disease Intervention/Treatment Phase
  • Drug: dimethyl fumarate
  • Drug: Placebo
 Phase 3

Detailed Description

The initial BG00012 dosage for the extension study (240 mg BID or 240 mg TID) was the same as that used in the Phase 3 Studies 109MS301 (NCT00420212) and 109MS302 (NCT00451451). Subsequent to the initiation of this study, BG00012 was approved in several countries for the treatment of MS at a dose of 240 mg BID. For this reason, all participants continuing in this study will receive the currently marketed dose of 240 mg BID.

Study Design

Study Type:
Interventional
Actual Enrollment :
1736 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Dose-Blind, Multicenter, Extension Study to Determine the Long-Term Safety and Efficacy of Two Doses of BG00012 Monotherapy in Subjects With Relapsing-Remitting Multiple Sclerosis
Actual Study Start Date :
Feb 3, 2009
Actual Primary Completion Date :
Nov 8, 2019
Actual Study Completion Date :
Nov 8, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: BG00012 plus placebo

In the first phase, participants will receive BG00012 240 mg (two 120 mg capsules) twice a day (BID) and 2 placebo capsules once a day. In the second phase participants will receive open-label BG00012 240 mg BID, for atleast 8 years.

Drug: dimethyl fumarate
BG00012 capsules
Other Names:
  • BG00012
  • Tecfidera
  • DMF

    • Drug: Placebo
    Capsules taken to maintain the blind in the 240 mg BID treatment group.
    Experimental: BG00012

    In the first phase participants will receive BG00012 240 mg (two 120 mg capsules) three times a day (TID). In the second phase participants will receive open-label BG00012 240 mg BID for atleast 8 years.

    Drug: dimethyl fumarate
    BG00012 capsules
    Other Names:
  • BG00012
  • Tecfidera
  • DMF

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Treatment-Emergent Adverse Events (AEs) [Day 1 up to Week 561]

      An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.

    Secondary Outcome Measures

    1. Percentage of Participants Who Had Relapses [Day 1 up to Week 384]

      Relapses were defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours.

    2. Annualized Relapse Rate (ARR) [Day 1 up to Week 384]

      The annualized relapse rate is calculated as the total number of relapses occurred during the period for all participants, divided by the total number of participant-years followed in the period.

    3. Change From Baseline in the Expanded Disability Status Scale (EDSS) at Week 384 [Baseline, Week 384]

      EDSS scale ranges from 0 (Normal neurological exam, no disability) to 10 (Death) in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist. Sustained disability progression was defined as at least a 1.0 point increase on the EDSS from a baseline EDSS ≥1.0 that was sustained for at least 24 weeks, or a 1.5 point increase on the EDSS from a baseline EDSS =0 that was sustained for at least 24 weeks.

    4. Number of Gadolinium (Gd)-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI) [Baseline up to Week 288]

      The Gd-enhancing lesions was evaluated using MRI technique.

    5. Volume of Gd-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI) [Baseline up to Week 288]

      The Gd-enhancing lesions was evaluated using MRI technique.

    6. Number of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI) [Baseline up to Week 288]

      The T2 lesions was evaluated using MRI technique.

    7. Volume of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI) [Baseline up to Week 288]

      The T2 lesions was evaluated using MRI technique.

    8. Number of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI) [Baseline up to Week 288]

      The T1 hypointense lesions was evaluated using MRI technique.

    9. Volume of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI) [Baseline up to Week 288]

      The T1 hypointense lesions was evaluated using MRI technique.

    10. Percent Change From Baseline in Brain Atrophy [Baseline up to Week 288]

      Brain atrophy was measured using magnetic resonance imaging (MRI) technique.

    11. Percent Change From Baseline in Magnetization Transfer Ratio (MTR) [Baseline up to Week 288]

      Magnetization Transfer Ratio (MTR) was measured using MRI technique.

    12. Change From Baseline in Short Form-36 Health Survey (SF-36®) at Week 384 [Baseline, Week 384]

      The SF-36 is a brief (36-item) scale reflecting the impact of both dysfunctions and general health perception the questionnaire measures: 1.physical function (PF),2. role physical (RF),3. bodily pain (BP),4. role emotional (RE),5. social function (SF), 6. general health (GH),7. vitality (VT), 8. mental health (MH). 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. The questions related to each dimension are scored on a scale from 0 (worst score) to 100 (best score), with higher scores indicating better function.

    13. Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - EQ-5D Index Score at Week 384 [Baseline, Week 384]

      The EQ-5D is a generic health-related quality of life instrument consisting of 2 components, EQ-5D index score and EQ-VAS. The EQ-5D provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has (1) "no problems", (2) "some problems", or (3) "severe problems". A positive change from baseline indicates improvement.

    14. Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - Visual Analog Scale (VAS) at Week 384 [Baseline, Week 384]

      The EQ-5D is a generic health-related quality of life instrument consisting of 2 components, EQ-5D index score and EQ-VAS. In EQ-VAS participants are asked to rate their current health on a 20 centimeter (cm) scale from 0 to 100 where 0 represents "worst imaginable health state" and 100 represents "best imaginable health state". A positive change from baseline indicates improvement.

    15. Change From Baseline in Visual Function Test Scores at Week 384 [Baseline, Week 384]

      Participants were tested using the contrast level of 100%, 2.5%, and 1.25% charts, and the scores were defined as the number of letters identified correctly for each chart (the maximum score was 60). Higher scores indicate better functioning. A positive change from baseline indicates better functioning.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    19 Years to 58 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Key Inclusion Criteria:

    -Subjects who participated in and completed as per protocol previous BG00012 clinical studies 109MS301 (NCT00420212) or 109MS302 (NCT00451451).

    Key Exclusion Criteria:

    • Any significant change in medical history from 109MS301 or 109MS302 that would have excluded subject's participation from their previous study.

    • Subjects from 109MS301 or 109MS302 who discontinued oral study treatment due to an AE or due to reasons other than protocol-defined relapse/disability progression.

    • Subjects from 109MS301 or 109MS302 who discontinued study treatment due to disability progression or relapses and did not follow the modified visit schedule up to Week 96.

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

    Contacts and Locations

    Locations

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    246 Research Site Stoke on Trent United Kingdom ST4 6QG

    Sponsors and Collaborators

    • Biogen

    Investigators

    • Study Director: Medical Director, Biogen

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Biogen
    ClinicalTrials.gov Identifier:
    NCT00835770
    Other Study ID Numbers:
    • 109MS303
    • 2008-004753-14
    First Posted:
    Feb 4, 2009
    Last Update Posted:
    Dec 31, 2020
    Last Verified:
    Dec 1, 2020
    Keywords provided by Biogen
    relapsing
    multiple sclerosis
    remitting
    oral
    Additional relevant MeSH terms:
    Multiple Sclerosis
    Multiple Sclerosis, Relapsing-Remitting
    Sclerosis
    Dimethyl Fumarate

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled at 298 investigative sites from 03 February 2009 to 08 November 2019.
    Pre-assignment Detail The study included participants who completed studies NCT00420212 and NCT00451451. A total of 1736 participants were treated in the open label phase extension study NCT00835770, out of which 759 completed the study.
    Arm/Group Title BG00012 240 mg BID BG00012 240 mg TID
    Arm/Group Description Participants received BG00012 240 milligram (mg), 2 capsules (120 mg each) orally, twice a day (BID) and 2 matching placebo capsules once a day (QD) for up to 8 years. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, three times a day (TID) for up to 8 years.
    Period Title: Overall Study
    STARTED 868 868
    COMPLETED 384 375
    NOT COMPLETED 484 493

    Baseline Characteristics

    Arm/Group Title BG00012 240 mg BID BG00012 240 mg TID Total
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Total of all reporting groups
    Overall Participants 868 868 1736
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    39.6
    (8.93)
    40.1
    (9.23)
    39.8
    (9.08)
    Sex: Female, Male (Count of Participants)
    Female
    616
    71%
    596
    68.7%
    1212
    69.8%
    Male
    252
    29%
    272
    31.3%
    524
    30.2%
    Race/Ethnicity, Customized (Count of Participants)
    White
    285
    32.8%
    309
    35.6%
    594
    34.2%
    Black or African American
    10
    1.2%
    16
    1.8%
    26
    1.5%
    Asian
    82
    9.4%
    80
    9.2%
    162
    9.3%
    Other
    32
    3.7%
    24
    2.8%
    56
    3.2%
    Not Reported Due To Confidentiality Regulations
    459
    52.9%
    439
    50.6%
    898
    51.7%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Treatment-Emergent Adverse Events (AEs)
    Description An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
    Time Frame Day 1 up to Week 561

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who had any post-baseline safety follow-up in study NCT00835770, defined as any treatment emergent AE in study NCT00835770 or any post-baseline laboratory, vital signs, or physical exam assessment in study NCT00835770, and received at least one dose of study treatment in study NCT00835770.
    Arm/Group Title BG00012 240 mg BID BG00012 240 mg TID
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years.
    Measure Participants 868 868
    Count of Participants [Participants]
    824
    94.9%
    814
    93.8%
    2. Secondary Outcome
    Title Percentage of Participants Who Had Relapses
    Description Relapses were defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours.
    Time Frame Day 1 up to Week 384

    Outcome Measure Data

    Analysis Population Description
    ITT population included participants who had entered study NCT00835770 and received at least one dose of study treatment. Data for this outcome measure (OM) was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 501 502 249 248 118 118
    Number [percentage of participants]
    40
    4.6%
    41
    4.7%
    34
    2%
    36
    NaN
    31
    NaN
    31
    NaN
    3. Secondary Outcome
    Title Annualized Relapse Rate (ARR)
    Description The annualized relapse rate is calculated as the total number of relapses occurred during the period for all participants, divided by the total number of participant-years followed in the period.
    Time Frame Day 1 up to Week 384

    Outcome Measure Data

    Analysis Population Description
    ITT population included participants who had entered study NCT00835770 and received at least one dose of study treatment. Data for this OM was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 501 502 249 248 118 118
    Number [relapses per participant-years]
    0.159
    0.179
    0.200
    0.199
    0.184
    0.212
    4. Secondary Outcome
    Title Change From Baseline in the Expanded Disability Status Scale (EDSS) at Week 384
    Description EDSS scale ranges from 0 (Normal neurological exam, no disability) to 10 (Death) in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist. Sustained disability progression was defined as at least a 1.0 point increase on the EDSS from a baseline EDSS ≥1.0 that was sustained for at least 24 weeks, or a 1.5 point increase on the EDSS from a baseline EDSS =0 that was sustained for at least 24 weeks.
    Time Frame Baseline, Week 384

    Outcome Measure Data

    Analysis Population Description
    ITT population included participants who had entered study NCT00835770 and received at least one dose of study treatment. 'Number Analyzed' =Number of participants analyzed at specific timepoint. Data for this OM was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 501 502 249 248 118 118
    Baseline
    2.44
    (1.251)
    2.43
    (1.144)
    2.50
    (1.135)
    2.54
    (1.218)
    2.57
    (1.249)
    2.68
    (1.231)
    Change at Week 384
    0.28
    (1.160)
    0.26
    (1.213)
    0.37
    (1.328)
    0.53
    (1.278)
    0.39
    (1.217)
    0.49
    (1.319)
    5. Secondary Outcome
    Title Number of Gadolinium (Gd)-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI)
    Description The Gd-enhancing lesions was evaluated using MRI technique.
    Time Frame Baseline up to Week 288

    Outcome Measure Data

    Analysis Population Description
    MRI population. 'Number Analyzed' =Number of participants analyzed at specific timepoint. Data for this OM was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 213 222 105 103 49 60
    Week 48
    0.4
    (1.87)
    0.4
    (1.29)
    0.2
    (0.66)
    0.3
    (1.14)
    0.5
    (1.19)
    0.4
    (1.14)
    Week 96
    0.4
    (1.77)
    0.4
    (1.28)
    0.1
    (0.38)
    0.2
    (0.82)
    0.6
    (1.33)
    0.3
    (0.73)
    Week 144
    0.3
    (1.66)
    0.4
    (1.30)
    0.2
    (0.44)
    0.1
    (0.29)
    0.5
    (2.48)
    0.3
    (1.59)
    Week 192
    0.4
    (2.02)
    0.5
    (1.85)
    0.5
    (1.72)
    0.3
    (0.96)
    0.2
    (0.60)
    0.6
    (2.01)
    Week 240
    0.5
    (3.14)
    0.5
    (2.29)
    0.2
    (0.50)
    0.2
    (0.51)
    0.2
    (0.58)
    0.3
    (0.75)
    Week 288
    0.2
    (0.74)
    0.5
    (1.81)
    0.1
    (0.40)
    0.7
    (2.76)
    0.0
    (0.00)
    0.3
    (0.77)
    6. Secondary Outcome
    Title Volume of Gd-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI)
    Description The Gd-enhancing lesions was evaluated using MRI technique.
    Time Frame Baseline up to Week 288

    Outcome Measure Data

    Analysis Population Description
    MRI population. 'Number Analyzed' =Number of participants analyzed at specific timepoint. Data for this OM was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 213 222 105 103 49 60
    Baseline
    31.7
    (179.28)
    48.6
    (205.43)
    96.0
    (260.79)
    142.5
    (459.76)
    37.1
    (138.82)
    41.7
    (116.55)
    Week 48
    59.6
    (526.51)
    70.0
    (366.63)
    18.8
    (91.47)
    25.3
    (108.19)
    42.5
    (123.67)
    42.7
    (148.11)
    Week 96
    49.1
    (245.14)
    56.1
    (271.29)
    27.7
    (204.80)
    13.3
    (67.01)
    64.3
    (183.16)
    22.3
    (60.83)
    Week 144
    44.1
    (291.14)
    47.0
    (169.68)
    18.8
    (66.15)
    3.8
    (25.03)
    42.6
    (142.55)
    92.9
    (397.69)
    Week 192
    39.1
    (217.89)
    54.5
    (251.31)
    45.8
    (156.88)
    19.9
    (79.19)
    12.0
    (40.56)
    55.1
    (169.16)
    Week 240
    96.8
    (650.06)
    69.3
    (374.67)
    21.7
    (77.87)
    14.1
    (45.22)
    17.5
    (46.19)
    17.1
    (48.41)
    Week 288
    18.2
    (93.28)
    53.1
    (250.87)
    7.9
    (30.09)
    230.2
    (1092.11)
    0.0
    (0.00)
    34.1
    (102.87)
    7. Secondary Outcome
    Title Number of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI)
    Description The T2 lesions was evaluated using MRI technique.
    Time Frame Baseline up to Week 288

    Outcome Measure Data

    Analysis Population Description
    MRI population. 'Number Analyzed' =Number of participants analyzed at specific timepoint. Data for this OM was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 213 222 105 103 49 60
    Week 48
    1.6
    (4.07)
    2.2
    (6.15)
    2.7
    (4.96)
    2.4
    (5.45)
    3.4
    (6.57)
    2.1
    (3.83)
    Week 96
    3.4
    (8.35)
    4.1
    (10.01)
    3.8
    (7.24)
    2.9
    (6.78)
    4.9
    (8.51)
    3.4
    (5.13)
    Week 144
    4.2
    (9.81)
    5.2
    (10.01)
    4.0
    (7.27)
    4.3
    (10.12)
    5.7
    (9.45)
    5.2
    (9.68)
    Week 192
    5.8
    (14.04)
    7.5
    (15.14)
    5.6
    (10.09)
    5.6
    (14.19)
    5.5
    (9.94)
    5.6
    (13.35)
    Week 240
    7.4
    (17.09)
    9.5
    (20.33)
    8.2
    (14.87)
    7.7
    (17.89)
    6.8
    (11.74)
    7.5
    (16.76)
    Week 288
    8.2
    (18.53)
    12.4
    (28.23)
    7.5
    (13.89)
    10.4
    (22.05)
    8.9
    (15.04)
    6.0
    (8.90)
    8. Secondary Outcome
    Title Volume of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI)
    Description The T2 lesions was evaluated using MRI technique.
    Time Frame Baseline up to Week 288

    Outcome Measure Data

    Analysis Population Description
    MRI population. 'Number Analyzed' =Number of participants analyzed at specific timepoint. Data for this OM was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 213 222 105 103 49 60
    Baseline
    10231.9
    (11214.17)
    10408.3
    (12166.80)
    8883.7
    (8570.10)
    10806.3
    (12060.05)
    12628.9
    (11258.69)
    13044.4
    (14608.50)
    Week 48
    9951.9
    (10750.15)
    9849.6
    (10986.36)
    8992.1
    (7952.13)
    10114.5
    (10121.61)
    11160.7
    (9565.55)
    12979.0
    (14415.86)
    Week 96
    10331.3
    (11359.81)
    10434.0
    (12201.38)
    8645.2
    (7787.60)
    9985.7
    (10715.73)
    11318.1
    (9873.73)
    13974.1
    (15432.10)
    Week 144
    9930.1
    (10686.26)
    10280.7
    (11324.58)
    8829.4
    (7482.93)
    9792.3
    (9842.28)
    10188.5
    (8064.09)
    12949.7
    (14036.15)
    Week 192
    9837.7
    (10845.04)
    10760.0
    (11987.16)
    9077.6
    (7794.52)
    10576.3
    (12029.26)
    10421.9
    (8773.41)
    11671.5
    (13124.47)
    Week 240
    10611.2
    (11633.95)
    11087.5
    (12464.90)
    9711.1
    (8709.46)
    10591.4
    (11613.26)
    11009.9
    (9551.94)
    12254.4
    (13732.10)
    Week 288
    9611.8
    (9447.18)
    9800.8
    (11279.84)
    8819.8
    (8866.90)
    10537.6
    (10684.47)
    11586.3
    (9728.19)
    10404.8
    (12245.75)
    9. Secondary Outcome
    Title Number of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI)
    Description The T1 hypointense lesions was evaluated using MRI technique.
    Time Frame Baseline up to Week 288

    Outcome Measure Data

    Analysis Population Description
    MRI population. 'Number Analyzed' =Number of participants analyzed at specific timepoint. Data for this OM was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 213 222 105 103 49 60
    Week 48
    0.8
    (2.13)
    1.0
    (2.37)
    1.8
    (3.81)
    1.7
    (3.71)
    2.0
    (4.22)
    1.3
    (2.64)
    Week 96
    1.7
    (3.63)
    1.9
    (3.91)
    1.8
    (3.33)
    2.1
    (5.00)
    3.0
    (5.85)
    1.9
    (3.44)
    Week 144
    2.0
    (4.61)
    2.8
    (5.19)
    2.0
    (3.69)
    2.6
    (7.02)
    3.1
    (6.20)
    2.9
    (5.19)
    Week 192
    2.9
    (7.03)
    3.4
    (6.79)
    2.9
    (5.12)
    3.8
    (10.71)
    3.3
    (6.74)
    3.0
    (7.14)
    Week 240
    3.4
    (8.25)
    4.8
    (9.39)
    4.0
    (7.52)
    4.9
    (13.30)
    4.0
    (8.06)
    4.2
    (10.20)
    Week 288
    2.7
    (5.72)
    5.9
    (12.02)
    4.5
    (7.38)
    3.6
    (4.51)
    1.0
    (1.10)
    5.6
    (6.81)
    10. Secondary Outcome
    Title Volume of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI)
    Description The T1 hypointense lesions was evaluated using MRI technique.
    Time Frame Baseline up to Week 288

    Outcome Measure Data

    Analysis Population Description
    MRI population. 'Number Analyzed' =Number of participants analyzed at specific timepoint. Data for this OM was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 213 222 105 103 49 60
    Baseline
    3640.1
    (5598.31)
    3447.3
    (4900.96)
    2754.2
    (3552.30)
    3623.1
    (5549.13)
    3204.3
    (4221.55)
    3572.6
    (4915.24)
    Week 48
    3829.5
    (5824.26)
    3715.5
    (5112.21)
    2891.9
    (3034.00)
    3936.0
    (5271.89)
    3271.0
    (4157.24)
    3743.3
    (5374.24)
    Week 96
    3841.2
    (5682.74)
    3853.7
    (5428.66)
    2921.0
    (3327.93)
    3849.4
    (5167.13)
    3510.4
    (4672.80)
    3949.7
    (5018.63)
    Week 144
    3767.4
    (4969.23)
    4074.0
    (5413.85)
    3145.6
    (3366.27)
    4006.9
    (5062.08)
    3499.2
    (4198.50)
    4126.1
    (5695.44)
    Week 192
    3834.9
    (4942.19)
    4177.4
    (5301.68)
    3385.4
    (3575.44)
    4330.0
    (5136.67)
    3592.0
    (4069.39)
    4089.3
    (4996.13)
    Week 240
    4038.6
    (5145.85)
    4238.2
    (5248.84)
    3406.4
    (3936.73)
    3823.9
    (4274.82)
    3503.4
    (3933.75)
    4057.7
    (5223.62)
    Week 288
    3603.3
    (4394.60)
    3973.1
    (5202.05)
    3350.6
    (4140.34)
    4187.5
    (4835.43)
    3264.9
    (3639.91)
    2959.1
    (3918.62)
    11. Secondary Outcome
    Title Percent Change From Baseline in Brain Atrophy
    Description Brain atrophy was measured using magnetic resonance imaging (MRI) technique.
    Time Frame Baseline up to Week 288

    Outcome Measure Data

    Analysis Population Description
    MRI population. 'Number Analyzed' =Number of participants analyzed at specific timepoint. Data for this OM was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 213 222 105 103 49 60
    Change at Week 48
    -1.206
    (1.1006)
    -1.263
    (1.0848)
    -1.487
    (1.3086)
    -1.320
    (1.4021)
    -1.496
    (1.1316)
    -1.414
    (1.1882)
    Change at Week 96
    -1.372
    (1.1382)
    -1.500
    (1.0893)
    -1.589
    (1.3630)
    -1.775
    (1.7191)
    -1.883
    (1.2383)
    -1.810
    (1.4556)
    Change at Week 144
    -1.708
    (1.4109)
    -1.876
    (1.2604)
    -2.139
    (1.5884)
    -2.353
    (1.7897)
    -2.386
    (1.3168)
    -2.252
    (2.2124)
    Change at Week 192
    -2.138
    (1.6831)
    -2.117
    (1.4000)
    -2.230
    (1.7755)
    -2.476
    (1.7062)
    -2.645
    (1.2284)
    -2.417
    (2.0486)
    Change at Week 240
    -2.313
    (1.6309)
    -2.253
    (1.3721)
    -2.271
    (1.4817)
    -2.593
    (1.9043)
    -2.249
    (1.2985)
    -2.790
    (2.2188)
    Change at Week 288
    -2.216
    (1.5744)
    -2.271
    (1.2193)
    -2.470
    (1.6757)
    -2.849
    (1.9648)
    -2.657
    (1.7051)
    -2.496
    (1.3699)
    12. Secondary Outcome
    Title Percent Change From Baseline in Magnetization Transfer Ratio (MTR)
    Description Magnetization Transfer Ratio (MTR) was measured using MRI technique.
    Time Frame Baseline up to Week 288

    Outcome Measure Data

    Analysis Population Description
    MRI population. 'Number Analyzed' =Number of participants analyzed at specific timepoint. Data for this OM was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 213 222 105 103 49 60
    Change at Week 48
    -0.325
    (5.4932)
    -0.383
    (4.8621)
    1.034
    (7.3548)
    -0.567
    (4.4766)
    -0.081
    (13.6416)
    -0.334
    (1.5103)
    Change at Week 96
    -0.427
    (6.6493)
    -0.532
    (4.9880)
    1.630
    (7.6584)
    -0.947
    (7.0771)
    -4.269
    (12.6065)
    0.215
    (1.4270)
    Change at Week 144
    -0.042
    (9.2548)
    0.509
    (7.2692)
    1.525
    (8.6421)
    1.411
    (12.2825)
    -4.460
    (10.3887)
    3.119
    (8.1676)
    Change at Week 192
    1.038
    (10.8680)
    0.955
    (8.6105)
    3.012
    (9.3831)
    3.103
    (13.0046)
    1.384
    (15.7611)
    3.841
    (10.8600)
    Change at Week 240
    -0.002
    (15.6190)
    1.647
    (8.3094)
    3.213
    (9.6621)
    4.108
    (13.8103)
    2.959
    (16.8386)
    0.673
    (25.9962)
    Change at Week 288
    0.002
    (4.0206)
    -0.391
    (4.6415)
    -0.666
    (2.0741)
    -0.622
    (2.2922)
    -0.466
    (0.9410)
    -1.114
    (2.4539)
    13. Secondary Outcome
    Title Change From Baseline in Short Form-36 Health Survey (SF-36®) at Week 384
    Description The SF-36 is a brief (36-item) scale reflecting the impact of both dysfunctions and general health perception the questionnaire measures: 1.physical function (PF),2. role physical (RF),3. bodily pain (BP),4. role emotional (RE),5. social function (SF), 6. general health (GH),7. vitality (VT), 8. mental health (MH). 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. The questions related to each dimension are scored on a scale from 0 (worst score) to 100 (best score), with higher scores indicating better function.
    Time Frame Baseline, Week 384

    Outcome Measure Data

    Analysis Population Description
    ITT population included participants who had entered study NCT00835770 and received at least one dose of study treatment. 'Number Analyzed' =Number of participants analyzed at specific timepoint. Data for this OM was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 501 502 249 248 118 118
    Baseline: Physical Functioning Score
    68.48
    (25.938)
    71.78
    (24.849)
    69.67
    (24.481)
    67.97
    (26.279)
    69.10
    (25.226)
    68.20
    (25.370)
    Change at Week 384: Physical Functioning Score
    0.73
    (21.972)
    -4.79
    (24.641)
    -7.37
    (22.253)
    -6.89
    (23.194)
    -6.19
    (21.719)
    -6.25
    (28.350)
    Baseline: Role-Physical Score
    56.46
    (41.254)
    58.42
    (41.280)
    56.35
    (40.896)
    59.87
    (41.747)
    55.26
    (40.390)
    53.57
    (42.029)
    Change at Week 384: Role-Physical Score
    3.20
    (48.259)
    -2.75
    (47.283)
    -10.00
    (43.188)
    -8.24
    (53.177)
    -12.21
    (40.595)
    -1.04
    (54.568)
    Baseline: Bodily-Pain Score
    69.68
    (25.587)
    70.42
    (24.688)
    68.51
    (26.163)
    69.44
    (26.016)
    69.30
    (25.766)
    68.59
    (26.102)
    Change at Week 384: Bodily-Pain Score
    1.32
    (28.525)
    -1.47
    (25.779)
    -2.92
    (23.486)
    -4.36
    (25.935)
    -3.60
    (22.138)
    -4.46
    (33.297)
    Baseline: General Health Score
    53.99
    (21.563)
    55.44
    (20.768)
    54.45
    (18.690)
    52.42
    (20.028)
    51.21
    (18.707)
    52.58
    (19.675)
    Change at Week 384: General Health Score
    0.87
    (18.744)
    -2.12
    (20.595)
    -2.28
    (16.752)
    -0.52
    (22.035)
    -5.64
    (18.270)
    1.21
    (21.674)
    Baseline: Vitality Score
    50.48
    (20.966)
    52.21
    (19.842)
    50.63
    (19.130)
    50.64
    (21.069)
    51.30
    (19.703)
    50.33
    (20.019)
    Change at Week 384: Vitality Score
    1.11
    (19.857)
    -0.73
    (19.033)
    -4.67
    (17.934)
    0.40
    (20.822)
    -6.71
    (20.236)
    1.03
    (19.829)
    Baseline: Social Functioning Score
    71.46
    (24.451)
    71.53
    (24.394)
    69.67
    (24.581)
    72.23
    (24.699)
    69.02
    (24.688)
    69.53
    (25.100)
    Change at Week 384: Social Functioning Score
    -2.16
    (25.575)
    -3.30
    (24.912)
    -5.69
    (22.184)
    -2.08
    (27.724)
    -10.76
    (34.350)
    -0.52
    (25.780)
    Baseline: Role-Emotional Score
    64.87
    (40.653)
    65.57
    (40.015)
    62.86
    (42.715)
    62.61
    (41.280)
    60.29
    (41.393)
    64.26
    (41.854)
    Change at Week 384: Role-Emotional Score
    0.43
    (49.950)
    0.47
    (43.513)
    -12.22
    (42.532)
    4.17
    (44.656)
    -13.18
    (42.501)
    -3.55
    (48.769)
    Baseline: Mental Health Score
    65.01
    (19.818)
    66.24
    (19.060)
    65.42
    (17.658)
    65.15
    (19.233)
    62.30
    (17.347)
    63.61
    (18.414)
    Change at Week 384: Mental Health Score
    1.32
    (19.715)
    2.31
    (18.095)
    -3.91
    (19.897)
    2.33
    (17.524)
    -0.29
    (21.989)
    -2.06
    (20.066)
    Baseline: Mental Component Score
    45.40
    (11.130)
    45.63
    (10.272)
    45.13
    (10.932)
    45.31
    (10.907)
    44.00
    (10.702)
    45.03
    (10.642)
    Change at Week 384: Mental Component Score
    0.05
    (12.415)
    0.87
    (10.028)
    -2.55
    (10.328)
    1.97
    (10.657)
    -2.59
    (12.895)
    0.08
    (10.328)
    Baseline: Physical Component Score
    43.53
    (9.884)
    44.44
    (10.048)
    43.74
    (9.739)
    43.56
    (10.267)
    43.68
    (10.359)
    43.15
    (10.091)
    Change at Week 384: Physical Component Score
    0.55
    (9.373)
    -1.94
    (10.532)
    -2.29
    (8.929)
    -3.25
    (9.998)
    -2.70
    (8.860)
    -1.59
    (10.765)
    14. Secondary Outcome
    Title Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - EQ-5D Index Score at Week 384
    Description The EQ-5D is a generic health-related quality of life instrument consisting of 2 components, EQ-5D index score and EQ-VAS. The EQ-5D provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has (1) "no problems", (2) "some problems", or (3) "severe problems". A positive change from baseline indicates improvement.
    Time Frame Baseline, Week 384

    Outcome Measure Data

    Analysis Population Description
    ITT population included participants who had entered study NCT00835770 and received at least one dose of study treatment. 'Number Analyzed' =Number of participants analyzed at specific timepoint. Data for this OM was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 501 502 249 248 118 118
    Baseline
    0.73
    (0.210)
    0.73
    (0.222)
    0.72
    (0.223)
    0.71
    (0.244)
    0.71
    (0.246)
    0.72
    (0.189)
    Change at Week 384
    0.01
    (0.251)
    0.00
    (0.233)
    -0.07
    (0.269)
    0.00
    (0.249)
    -0.04
    (0.253)
    -0.03
    (0.241)
    15. Secondary Outcome
    Title Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - Visual Analog Scale (VAS) at Week 384
    Description The EQ-5D is a generic health-related quality of life instrument consisting of 2 components, EQ-5D index score and EQ-VAS. In EQ-VAS participants are asked to rate their current health on a 20 centimeter (cm) scale from 0 to 100 where 0 represents "worst imaginable health state" and 100 represents "best imaginable health state". A positive change from baseline indicates improvement.
    Time Frame Baseline, Week 384

    Outcome Measure Data

    Analysis Population Description
    ITT population included participants who had entered study NCT00835770 and received at least one dose of study treatment. 'Number Analyzed' =Number of participants analyzed at specific timepoint. Data for this OM was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 501 502 249 248 118 118
    Baseline
    70.97
    (18.460)
    70.48
    (19.993)
    70.40
    (17.630)
    69.44
    (19.907)
    66.80
    (18.846)
    69.07
    (20.094)
    Change at Week 384
    -0.48
    (19.631)
    -1.67
    (18.855)
    -7.24
    (18.419)
    -3.17
    (22.003)
    -1.71
    (25.330)
    -4.11
    (16.270)
    16. Secondary Outcome
    Title Change From Baseline in Visual Function Test Scores at Week 384
    Description Participants were tested using the contrast level of 100%, 2.5%, and 1.25% charts, and the scores were defined as the number of letters identified correctly for each chart (the maximum score was 60). Higher scores indicate better functioning. A positive change from baseline indicates better functioning.
    Time Frame Baseline, Week 384

    Outcome Measure Data

    Analysis Population Description
    ITT population included participants who had entered study NCT00835770 and received at least one dose of study treatment. 'Number Analyzed' =Number of participants analyzed at specific timepoint. Data for this OM was summarized as per treatment received in previous studies (NCT00420212 and NCT00451451).
    Arm/Group Title BG00012 240 mg BID (Prior BG00012 240 mg BID) BG00012 240 mg TID (Prior BG00012 240 mg TID) BG00012 240 mg BID (Prior BG00012 Matched Placebo) BG00012 240 mg TID (Prior BG00012 Matched Placebo) BG00012 240 mg BID (Prior Glatiramer Acetate [GA]) BG00012 240 mg TID (Prior Glatiramer Acetate [GA])
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received BG00012 240 mg BID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received BG00012 240 mg TID in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received placebo matched to BG00012 in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants who had received Glatiramer Acetate (GA) in the previous studies were included in this arm group. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years. Participants who had received GA in the previous studies were included in this arm group.
    Measure Participants 501 502 249 248 118 118
    Baseline: 100% Chart
    54.7
    (7.95)
    55.0
    (7.84)
    55.1
    (7.26)
    54.8
    (7.12)
    54.3
    (8.26)
    55.0
    (6.73)
    Change at Week 384: 100% Chart
    -0.4
    (6.76)
    -1.9
    (6.81)
    -1.4
    (8.48)
    -1.2
    (7.53)
    -1.6
    (8.05)
    -0.7
    (5.17)
    Baseline: 2.5% Chart
    32.4
    (12.17)
    32.6
    (11.76)
    32.4
    (11.42)
    32.3
    (11.99)
    31.8
    (12.36)
    31.7
    (12.41)
    Change at Week 384: 2.5% Chart
    -2.4
    (10.77)
    -3.3
    (10.43)
    -1.5
    (11.77)
    -4.9
    (11.14)
    -4.0
    (11.90)
    -2.1
    (9.86)
    Baseline: 1.25% Chart
    24.1
    (12.45)
    24.2
    (12.28)
    23.8
    (12.11)
    23.7
    (12.96)
    23.4
    (11.76)
    22.2
    (13.25)
    Change at Week 384: 1.25% Chart
    -5.8
    (13.39)
    -6.0
    (11.77)
    -4.1
    (13.04)
    -7.4
    (12.42)
    -6.7
    (13.78)
    -5.0
    (12.74)

    Adverse Events

    Time Frame From start of the study up to follow-up (up to Week 561)
    Adverse Event Reporting Description Safety population included all participants who had any post-baseline safety follow-up in study NCT00835770, defined as any treatment emergent AE in Study NCT00835770 or any post-baseline laboratory, vital signs, or physical exam assessment in study NCT00835770, and received at least one dose of study treatment in study NCT00835770.
    Arm/Group Title BG00012 240 mg BID BG00012 240 mg TID
    Arm/Group Description Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, BID and 2 matching placebo capsules QD for up to 8 years. Participants received BG00012 240 mg, 2 capsules (120 mg each) orally, TID for up to 8 years.
    All Cause Mortality
    BG00012 240 mg BID BG00012 240 mg TID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 5/868 (0.6%) 6/868 (0.7%)
    Serious Adverse Events
    BG00012 240 mg BID BG00012 240 mg TID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 279/868 (32.1%) 272/868 (31.3%)
    Blood and lymphatic system disorders
    Anaemia 0/868 (0%) 1/868 (0.1%)
    Eosinophilia 0/868 (0%) 1/868 (0.1%)
    Iron deficiency anaemia 2/868 (0.2%) 0/868 (0%)
    Leukopenia 1/868 (0.1%) 0/868 (0%)
    Lymphopenia 1/868 (0.1%) 1/868 (0.1%)
    Neutropenia 0/868 (0%) 1/868 (0.1%)
    Thrombocytopenia 1/868 (0.1%) 1/868 (0.1%)
    Cardiac disorders
    Acute coronary syndrome 1/868 (0.1%) 0/868 (0%)
    Acute myocardial infarction 1/868 (0.1%) 0/868 (0%)
    Atrial fibrillation 2/868 (0.2%) 1/868 (0.1%)
    Cardiac arrest 0/868 (0%) 2/868 (0.2%)
    Cardiac failure congestive 1/868 (0.1%) 0/868 (0%)
    Coronary artery disease 2/868 (0.2%) 0/868 (0%)
    Left ventricular dysfunction 1/868 (0.1%) 0/868 (0%)
    Mitral valve prolapse 1/868 (0.1%) 0/868 (0%)
    Myocardial infarction 1/868 (0.1%) 5/868 (0.6%)
    Myocardial ischaemia 0/868 (0%) 1/868 (0.1%)
    Wolff-parkinson-white syndrome 1/868 (0.1%) 0/868 (0%)
    Congenital, familial and genetic disorders
    Cytogenetic abnormality 0/868 (0%) 1/868 (0.1%)
    Limb malformation 1/868 (0.1%) 0/868 (0%)
    Ear and labyrinth disorders
    Hypoacusis 0/868 (0%) 1/868 (0.1%)
    Sudden hearing loss 0/868 (0%) 1/868 (0.1%)
    Vertigo positional 0/868 (0%) 1/868 (0.1%)
    Endocrine disorders
    Autoimmune thyroiditis 0/868 (0%) 1/868 (0.1%)
    Basedow's disease 2/868 (0.2%) 0/868 (0%)
    Goitre 0/868 (0%) 1/868 (0.1%)
    Hyperthyroidism 1/868 (0.1%) 0/868 (0%)
    Eye disorders
    Cataract 1/868 (0.1%) 0/868 (0%)
    Glaucoma 1/868 (0.1%) 0/868 (0%)
    Retinal ischaemia 0/868 (0%) 1/868 (0.1%)
    Ulcerative keratitis 0/868 (0%) 1/868 (0.1%)
    Vision blurred 0/868 (0%) 1/868 (0.1%)
    Gastrointestinal disorders
    Abdominal hernia 1/868 (0.1%) 0/868 (0%)
    Abdominal pain 0/868 (0%) 1/868 (0.1%)
    Colitis 0/868 (0%) 1/868 (0.1%)
    Colitis ulcerative 1/868 (0.1%) 1/868 (0.1%)
    Crohn's disease 0/868 (0%) 1/868 (0.1%)
    Diarrhoea 1/868 (0.1%) 0/868 (0%)
    Duodenal ulcer 0/868 (0%) 1/868 (0.1%)
    Duodenal ulcer perforation 1/868 (0.1%) 0/868 (0%)
    Duodenitis 0/868 (0%) 1/868 (0.1%)
    Gastric haemorrhage 1/868 (0.1%) 0/868 (0%)
    Gastritis 2/868 (0.2%) 3/868 (0.3%)
    Gastrointestinal haemorrhage 0/868 (0%) 1/868 (0.1%)
    Gastrointestinal inflammation 1/868 (0.1%) 0/868 (0%)
    Gastrointestinal mucosal disorder 1/868 (0.1%) 0/868 (0%)
    Gastrointestinal necrosis 1/868 (0.1%) 0/868 (0%)
    Gastrooesophageal reflux disease 1/868 (0.1%) 1/868 (0.1%)
    Haemorrhoids 0/868 (0%) 1/868 (0.1%)
    Inguinal hernia 1/868 (0.1%) 3/868 (0.3%)
    Intestinal haemorrhage 0/868 (0%) 1/868 (0.1%)
    Intestinal obstruction 0/868 (0%) 1/868 (0.1%)
    Pancreatitis 1/868 (0.1%) 0/868 (0%)
    Peritonitis 1/868 (0.1%) 0/868 (0%)
    Small intestinal obstruction 1/868 (0.1%) 0/868 (0%)
    Subileus 1/868 (0.1%) 0/868 (0%)
    Umbilical hernia 2/868 (0.2%) 0/868 (0%)
    Volvulus 0/868 (0%) 1/868 (0.1%)
    General disorders
    Capsular contracture associated with breast implant 1/868 (0.1%) 0/868 (0%)
    Chest pain 0/868 (0%) 1/868 (0.1%)
    Gait disturbance 1/868 (0.1%) 0/868 (0%)
    Impaired healing 1/868 (0.1%) 0/868 (0%)
    Non-cardiac chest pain 0/868 (0%) 3/868 (0.3%)
    Oedema peripheral 0/868 (0%) 1/868 (0.1%)
    Pyrexia 3/868 (0.3%) 1/868 (0.1%)
    Serositis 0/868 (0%) 1/868 (0.1%)
    Treatment failure 0/868 (0%) 1/868 (0.1%)
    Hepatobiliary disorders
    Bile duct stone 1/868 (0.1%) 1/868 (0.1%)
    Biliary colic 0/868 (0%) 2/868 (0.2%)
    Cholecystitis 3/868 (0.3%) 1/868 (0.1%)
    Cholecystitis acute 1/868 (0.1%) 1/868 (0.1%)
    Cholecystitis chronic 0/868 (0%) 2/868 (0.2%)
    Cholelithiasis 2/868 (0.2%) 7/868 (0.8%)
    Chronic hepatitis 1/868 (0.1%) 0/868 (0%)
    Hepatic failure 0/868 (0%) 1/868 (0.1%)
    Immune system disorders
    Anaphylactic reaction 0/868 (0%) 1/868 (0.1%)
    Drug hypersensitivity 1/868 (0.1%) 0/868 (0%)
    Infections and infestations
    Appendicitis 2/868 (0.2%) 4/868 (0.5%)
    Bacterial infection 1/868 (0.1%) 0/868 (0%)
    Bacteriuria 1/868 (0.1%) 0/868 (0%)
    Bronchitis 1/868 (0.1%) 0/868 (0%)
    Bronchopneumonia 0/868 (0%) 2/868 (0.2%)
    Bronchopulmonary aspergillosis 1/868 (0.1%) 0/868 (0%)
    Cellulitis 2/868 (0.2%) 2/868 (0.2%)
    Chronic sinusitis 0/868 (0%) 2/868 (0.2%)
    Chronic tonsillitis 1/868 (0.1%) 0/868 (0%)
    Dengue fever 2/868 (0.2%) 0/868 (0%)
    Diarrhoea infectious 0/868 (0%) 1/868 (0.1%)
    Diverticulitis 1/868 (0.1%) 0/868 (0%)
    Endometritis 0/868 (0%) 1/868 (0.1%)
    Escherichia infection 1/868 (0.1%) 0/868 (0%)
    Gastroenteritis 2/868 (0.2%) 1/868 (0.1%)
    Gastroenteritis norovirus 0/868 (0%) 1/868 (0.1%)
    Gastroenteritis rotavirus 0/868 (0%) 1/868 (0.1%)
    Gastrointestinal bacterial infection 0/868 (0%) 1/868 (0.1%)
    Genital herpes 0/868 (0%) 1/868 (0.1%)
    Haematoma infection 1/868 (0.1%) 0/868 (0%)
    Herpes simplex 1/868 (0.1%) 0/868 (0%)
    Herpes zoster 1/868 (0.1%) 3/868 (0.3%)
    Infected skin ulcer 1/868 (0.1%) 0/868 (0%)
    Lower respiratory tract infection 0/868 (0%) 1/868 (0.1%)
    Meningitis viral 1/868 (0.1%) 0/868 (0%)
    Nasopharyngitis 1/868 (0.1%) 0/868 (0%)
    Oesophageal candidiasis 1/868 (0.1%) 0/868 (0%)
    Oral candidiasis 0/868 (0%) 1/868 (0.1%)
    Osteomyelitis 0/868 (0%) 1/868 (0.1%)
    Papilloma viral infection 1/868 (0.1%) 0/868 (0%)
    Pelvic abscess 0/868 (0%) 1/868 (0.1%)
    Peritonsillar abscess 0/868 (0%) 1/868 (0.1%)
    Peritonsillitis 0/868 (0%) 1/868 (0.1%)
    Pneumonia 6/868 (0.7%) 1/868 (0.1%)
    Pneumonia bacterial 0/868 (0%) 1/868 (0.1%)
    Post procedural infection 1/868 (0.1%) 0/868 (0%)
    Progressive multifocal leukoencephalopathy (PML) 0/868 (0%) 1/868 (0.1%)
    Pulmonary tuberculoma 0/868 (0%) 1/868 (0.1%)
    Pyelonephritis acute 0/868 (0%) 1/868 (0.1%)
    Pyelonephritis chronic 1/868 (0.1%) 0/868 (0%)
    Pyothorax 1/868 (0.1%) 0/868 (0%)
    Rectal abscess 1/868 (0.1%) 0/868 (0%)
    Respiratory tract infection 1/868 (0.1%) 0/868 (0%)
    Respiratory tract infection viral 1/868 (0.1%) 0/868 (0%)
    Scrub typhus 1/868 (0.1%) 0/868 (0%)
    Septic shock 1/868 (0.1%) 0/868 (0%)
    Sinusitis 2/868 (0.2%) 0/868 (0%)
    Subcutaneous abscess 1/868 (0.1%) 0/868 (0%)
    Tooth abscess 1/868 (0.1%) 0/868 (0%)
    Upper respiratory tract infection 1/868 (0.1%) 0/868 (0%)
    Urinary tract infection 10/868 (1.2%) 4/868 (0.5%)
    Urosepsis 0/868 (0%) 1/868 (0.1%)
    Vaginal infection 1/868 (0.1%) 0/868 (0%)
    Vestibular neuronitis 0/868 (0%) 1/868 (0.1%)
    Viral infection 1/868 (0.1%) 1/868 (0.1%)
    Injury, poisoning and procedural complications
    Accident 0/868 (0%) 1/868 (0.1%)
    Accident at work 1/868 (0.1%) 0/868 (0%)
    Acetabulum fracture 0/868 (0%) 1/868 (0.1%)
    Animal bite 0/868 (0%) 2/868 (0.2%)
    Ankle fracture 2/868 (0.2%) 2/868 (0.2%)
    Avulsion fracture 1/868 (0.1%) 0/868 (0%)
    Brain contusion 1/868 (0.1%) 0/868 (0%)
    Clavicle fracture 0/868 (0%) 1/868 (0.1%)
    Comminuted fracture 0/868 (0%) 1/868 (0.1%)
    Concussion 0/868 (0%) 1/868 (0.1%)
    Contusion 3/868 (0.3%) 1/868 (0.1%)
    Drug toxicity 0/868 (0%) 1/868 (0.1%)
    Fall 13/868 (1.5%) 18/868 (2.1%)
    Femoral neck fracture 3/868 (0.3%) 4/868 (0.5%)
    Femur fracture 3/868 (0.3%) 0/868 (0%)
    Fibula fracture 0/868 (0%) 3/868 (0.3%)
    Foot fracture 2/868 (0.2%) 0/868 (0%)
    Hand fracture 0/868 (0%) 1/868 (0.1%)
    Hip fracture 1/868 (0.1%) 1/868 (0.1%)
    Humerus fracture 0/868 (0%) 4/868 (0.5%)
    Incision site haematoma 1/868 (0.1%) 0/868 (0%)
    Incisional hernia 0/868 (0%) 1/868 (0.1%)
    Joint dislocation 1/868 (0.1%) 0/868 (0%)
    Joint injury 0/868 (0%) 1/868 (0.1%)
    Joint sprain 0/868 (0%) 1/868 (0.1%)
    Ligament injury 1/868 (0.1%) 0/868 (0%)
    Ligament rupture 2/868 (0.2%) 0/868 (0%)
    Lower limb fracture 1/868 (0.1%) 3/868 (0.3%)
    Lumbar vertebral fracture 0/868 (0%) 1/868 (0.1%)
    Meniscus lesion 1/868 (0.1%) 1/868 (0.1%)
    Multiple injuries 1/868 (0.1%) 0/868 (0%)
    Muscle rupture 0/868 (0%) 2/868 (0.2%)
    Overdose 2/868 (0.2%) 0/868 (0%)
    Postoperative hernia 1/868 (0.1%) 0/868 (0%)
    Pubis fracture 1/868 (0.1%) 0/868 (0%)
    Radius fracture 3/868 (0.3%) 0/868 (0%)
    Respiratory fume inhalation disorder 0/868 (0%) 1/868 (0.1%)
    Rib fracture 0/868 (0%) 2/868 (0.2%)
    Road traffic accident 4/868 (0.5%) 5/868 (0.6%)
    Skeletal injury 1/868 (0.1%) 1/868 (0.1%)
    Spinal compression fracture 0/868 (0%) 1/868 (0.1%)
    Splenic rupture 0/868 (0%) 1/868 (0.1%)
    Thoracic vertebral fracture 0/868 (0%) 2/868 (0.2%)
    Tibia fracture 1/868 (0.1%) 5/868 (0.6%)
    Ulna fracture 0/868 (0%) 1/868 (0.1%)
    Wound 1/868 (0.1%) 0/868 (0%)
    Investigations
    Anticoagulation drug level above therapeutic 0/868 (0%) 1/868 (0.1%)
    Investigation 1/868 (0.1%) 0/868 (0%)
    Lymphocyte count decreased 0/868 (0%) 1/868 (0.1%)
    Metabolism and nutrition disorders
    Dehydration 1/868 (0.1%) 1/868 (0.1%)
    Diabetes mellitus 1/868 (0.1%) 1/868 (0.1%)
    Hyperglycaemia 0/868 (0%) 1/868 (0.1%)
    Obesity 2/868 (0.2%) 1/868 (0.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/868 (0%) 1/868 (0.1%)
    Arthritis 1/868 (0.1%) 0/868 (0%)
    Back pain 4/868 (0.5%) 0/868 (0%)
    Bursitis 1/868 (0.1%) 0/868 (0%)
    Chondropathy 1/868 (0.1%) 0/868 (0%)
    Foot deformity 2/868 (0.2%) 2/868 (0.2%)
    Intervertebral disc degeneration 0/868 (0%) 1/868 (0.1%)
    Intervertebral disc disorder 1/868 (0.1%) 0/868 (0%)
    Intervertebral disc protrusion 5/868 (0.6%) 1/868 (0.1%)
    Musculoskeletal pain 0/868 (0%) 1/868 (0.1%)
    Myositis 1/868 (0.1%) 0/868 (0%)
    Osteoarthritis 5/868 (0.6%) 4/868 (0.5%)
    Osteonecrosis 1/868 (0.1%) 1/868 (0.1%)
    Pathological fracture 0/868 (0%) 1/868 (0.1%)
    Periarthritis 1/868 (0.1%) 3/868 (0.3%)
    Rhabdomyolysis 2/868 (0.2%) 0/868 (0%)
    Rotator cuff syndrome 2/868 (0.2%) 0/868 (0%)
    Spinal deformity 0/868 (0%) 1/868 (0.1%)
    Spondylolisthesis 1/868 (0.1%) 0/868 (0%)
    Synovitis 0/868 (0%) 1/868 (0.1%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenolymphoma 0/868 (0%) 1/868 (0.1%)
    Anal cancer 2/868 (0.2%) 0/868 (0%)
    Basal cell carcinoma 3/868 (0.3%) 2/868 (0.2%)
    Benign breast neoplasm 1/868 (0.1%) 0/868 (0%)
    Benign ovarian tumour 1/868 (0.1%) 0/868 (0%)
    Bowenoid papulosis 1/868 (0.1%) 0/868 (0%)
    Brain cancer metastatic 1/868 (0.1%) 0/868 (0%)
    Breast cancer 4/868 (0.5%) 8/868 (0.9%)
    Breast cancer in situ 1/868 (0.1%) 0/868 (0%)
    Breast cancer stage II 0/868 (0%) 1/868 (0.1%)
    Breast neoplasm 0/868 (0%) 1/868 (0.1%)
    Carcinoid tumour of the pancreas 1/868 (0.1%) 0/868 (0%)
    Cervix neoplasm 1/868 (0.1%) 0/868 (0%)
    Chronic myeloid leukaemia 0/868 (0%) 1/868 (0.1%)
    Endometrial cancer 1/868 (0.1%) 0/868 (0%)
    Fibroma 0/868 (0%) 1/868 (0.1%)
    Glioma 1/868 (0.1%) 0/868 (0%)
    Haemangioma 0/868 (0%) 1/868 (0.1%)
    Leiomyoma 0/868 (0%) 1/868 (0.1%)
    Lung adenocarcinoma stage II 1/868 (0.1%) 0/868 (0%)
    Lung squamous cell carcinoma stage unspecified 1/868 (0.1%) 0/868 (0%)
    Malignant melanoma 2/868 (0.2%) 2/868 (0.2%)
    Meningioma 1/868 (0.1%) 0/868 (0%)
    Mesothelioma malignant 1/868 (0.1%) 0/868 (0%)
    Metastatic malignant melanoma 1/868 (0.1%) 0/868 (0%)
    Metastatic neoplasm 1/868 (0.1%) 1/868 (0.1%)
    Pancreatic carcinoma 0/868 (0%) 1/868 (0.1%)
    Pharyngeal neoplasm benign 0/868 (0%) 1/868 (0.1%)
    Rectal cancer 0/868 (0%) 1/868 (0.1%)
    Renal cell carcinoma 3/868 (0.3%) 0/868 (0%)
    Salivary gland cancer 0/868 (0%) 1/868 (0.1%)
    Squamous cell carcinoma 1/868 (0.1%) 1/868 (0.1%)
    Squamous cell carcinoma of the cervix 1/868 (0.1%) 0/868 (0%)
    Squamous endometrial carcinoma 1/868 (0.1%) 0/868 (0%)
    Thyroid cancer 2/868 (0.2%) 1/868 (0.1%)
    Transitional cell carcinoma 0/868 (0%) 1/868 (0.1%)
    Uterine leiomyoma 6/868 (0.7%) 3/868 (0.3%)
    Nervous system disorders
    Cerebral haemorrhage 1/868 (0.1%) 0/868 (0%)
    Cerebral ischaemia 0/868 (0%) 1/868 (0.1%)
    Cerebrovascular insufficiency 1/868 (0.1%) 0/868 (0%)
    Cervicobrachial syndrome 0/868 (0%) 1/868 (0.1%)
    Complex partial seizures 0/868 (0%) 1/868 (0.1%)
    Convulsion 3/868 (0.3%) 2/868 (0.2%)
    Dementia 1/868 (0.1%) 0/868 (0%)
    Disturbance in attention 0/868 (0%) 1/868 (0.1%)
    Dysarthria 1/868 (0.1%) 0/868 (0%)
    Epilepsy 1/868 (0.1%) 1/868 (0.1%)
    Headache 1/868 (0.1%) 0/868 (0%)
    Hemiparesis 0/868 (0%) 1/868 (0.1%)
    Hypoaesthesia 0/868 (0%) 2/868 (0.2%)
    Intracranial aneurysm 1/868 (0.1%) 0/868 (0%)
    Lumbar radiculopathy 0/868 (0%) 1/868 (0.1%)
    Migraine 1/868 (0.1%) 1/868 (0.1%)
    Multiple sclerosis 4/868 (0.5%) 2/868 (0.2%)
    Multiple sclerosis relapse 116/868 (13.4%) 122/868 (14.1%)
    Muscle spasticity 1/868 (0.1%) 0/868 (0%)
    Neuralgia 1/868 (0.1%) 2/868 (0.2%)
    Optic neuritis 0/868 (0%) 2/868 (0.2%)
    Paraesthesia 0/868 (0%) 1/868 (0.1%)
    Paraparesis 2/868 (0.2%) 0/868 (0%)
    Parkinson's disease 1/868 (0.1%) 0/868 (0%)
    Quadriparesis 1/868 (0.1%) 0/868 (0%)
    Radiculitis 1/868 (0.1%) 0/868 (0%)
    Relapsing-remitting multiple sclerosis 2/868 (0.2%) 1/868 (0.1%)
    Sciatica 1/868 (0.1%) 1/868 (0.1%)
    Subarachnoid haemorrhage 1/868 (0.1%) 0/868 (0%)
    Syncope 2/868 (0.2%) 1/868 (0.1%)
    Transient global amnesia 1/868 (0.1%) 0/868 (0%)
    Trigeminal neuralgia 1/868 (0.1%) 2/868 (0.2%)
    Uhthoff's phenomenon 1/868 (0.1%) 0/868 (0%)
    Pregnancy, puerperium and perinatal conditions
    Abortion missed 0/868 (0%) 1/868 (0.1%)
    Abortion spontaneous 1/868 (0.1%) 1/868 (0.1%)
    Complication of pregnancy 1/868 (0.1%) 0/868 (0%)
    Psychiatric disorders
    Acute psychosis 1/868 (0.1%) 1/868 (0.1%)
    Alcoholism 1/868 (0.1%) 0/868 (0%)
    Anorexia nervosa 0/868 (0%) 1/868 (0.1%)
    Anxiety disorder 1/868 (0.1%) 0/868 (0%)
    Burnout syndrome 1/868 (0.1%) 0/868 (0%)
    Catatonia 1/868 (0.1%) 0/868 (0%)
    Completed suicide 0/868 (0%) 2/868 (0.2%)
    Delirium 0/868 (0%) 1/868 (0.1%)
    Depression 0/868 (0%) 3/868 (0.3%)
    Drug abuse 2/868 (0.2%) 0/868 (0%)
    Hallucination 1/868 (0.1%) 0/868 (0%)
    Major depression 0/868 (0%) 2/868 (0.2%)
    Mood disorder due to a general medical condition 1/868 (0.1%) 0/868 (0%)
    Morbid thoughts 1/868 (0.1%) 0/868 (0%)
    Neurosis 1/868 (0.1%) 0/868 (0%)
    Psychiatric decompensation 0/868 (0%) 1/868 (0.1%)
    Psychotic behaviour 1/868 (0.1%) 0/868 (0%)
    Psychotic disorder 0/868 (0%) 1/868 (0.1%)
    Psychotic disorder due to a general medical condition 0/868 (0%) 1/868 (0.1%)
    Stress 1/868 (0.1%) 0/868 (0%)
    Suicide attempt 1/868 (0.1%) 0/868 (0%)
    Renal and urinary disorders
    Haematuria 1/868 (0.1%) 0/868 (0%)
    Hydronephrosis 1/868 (0.1%) 1/868 (0.1%)
    Nephrolithiasis 1/868 (0.1%) 2/868 (0.2%)
    Nephrotic syndrome 1/868 (0.1%) 0/868 (0%)
    Neurogenic bladder 1/868 (0.1%) 0/868 (0%)
    Renal failure acute 1/868 (0.1%) 0/868 (0%)
    Reproductive system and breast disorders
    Breast necrosis 1/868 (0.1%) 0/868 (0%)
    Cervical dysplasia 0/868 (0%) 2/868 (0.2%)
    Cystocele 1/868 (0.1%) 0/868 (0%)
    Dysfunctional uterine bleeding 1/868 (0.1%) 0/868 (0%)
    Endometrial hyperplasia 1/868 (0.1%) 0/868 (0%)
    Endometriosis 0/868 (0%) 3/868 (0.3%)
    Fibrocystic breast disease 1/868 (0.1%) 0/868 (0%)
    Menorrhagia 1/868 (0.1%) 2/868 (0.2%)
    Metrorrhagia 1/868 (0.1%) 3/868 (0.3%)
    Ovarian cyst 2/868 (0.2%) 1/868 (0.1%)
    Ovarian cyst ruptured 0/868 (0%) 1/868 (0.1%)
    Pelvic adhesions 0/868 (0%) 1/868 (0.1%)
    Pelvic pain 0/868 (0%) 1/868 (0.1%)
    Uterine polyp 1/868 (0.1%) 1/868 (0.1%)
    Respiratory, thoracic and mediastinal disorders
    Asthma 1/868 (0.1%) 0/868 (0%)
    Choking 0/868 (0%) 1/868 (0.1%)
    Chronic obstructive pulmonary disease 2/868 (0.2%) 1/868 (0.1%)
    Paranasal cyst 0/868 (0%) 1/868 (0.1%)
    Pleural effusion 1/868 (0.1%) 0/868 (0%)
    Pleurisy 0/868 (0%) 1/868 (0.1%)
    Pneumonia aspiration 1/868 (0.1%) 0/868 (0%)
    Pulmonary artery thrombosis 1/868 (0.1%) 0/868 (0%)
    Pulmonary embolism 2/868 (0.2%) 1/868 (0.1%)
    Pulmonary sarcoidosis 0/868 (0%) 1/868 (0.1%)
    Skin and subcutaneous tissue disorders
    Decubitus ulcer 1/868 (0.1%) 0/868 (0%)
    Dermatitis allergic 0/868 (0%) 1/868 (0.1%)
    Skin ulcer 1/868 (0.1%) 0/868 (0%)
    Surgical and medical procedures
    Abdominoplasty 1/868 (0.1%) 0/868 (0%)
    Aortic valve replacement 1/868 (0.1%) 0/868 (0%)
    Appendicectomy 1/868 (0.1%) 0/868 (0%)
    Bladder neck suspension 0/868 (0%) 1/868 (0.1%)
    Bunion operation 0/868 (0%) 1/868 (0.1%)
    Caesarean section 0/868 (0%) 1/868 (0.1%)
    Carpal tunnel decompression 0/868 (0%) 1/868 (0.1%)
    Cholecystectomy 1/868 (0.1%) 0/868 (0%)
    Cochlea implant 0/868 (0%) 1/868 (0.1%)
    Cystocele repair 1/868 (0.1%) 0/868 (0%)
    Female sterilisation 1/868 (0.1%) 1/868 (0.1%)
    Hip arthroplasty 1/868 (0.1%) 0/868 (0%)
    Hysterectomy 0/868 (0%) 1/868 (0.1%)
    Knee arthroplasty 0/868 (0%) 1/868 (0.1%)
    Mammoplasty 1/868 (0.1%) 0/868 (0%)
    Medical device change 0/868 (0%) 1/868 (0.1%)
    Medical device removal 0/868 (0%) 1/868 (0.1%)
    Ovarian cystectomy 1/868 (0.1%) 0/868 (0%)
    Percutaneous coronary intervention 1/868 (0.1%) 0/868 (0%)
    Postoperative care 0/868 (0%) 1/868 (0.1%)
    Surgery 0/868 (0%) 1/868 (0.1%)
    Thyroidectomy 0/868 (0%) 1/868 (0.1%)
    Umbilical hernia repair 1/868 (0.1%) 0/868 (0%)
    Varicose vein operation 1/868 (0.1%) 0/868 (0%)
    Vascular disorders
    Circulatory collapse 1/868 (0.1%) 0/868 (0%)
    Deep vein thrombosis 1/868 (0.1%) 1/868 (0.1%)
    Hypertension 1/868 (0.1%) 0/868 (0%)
    Hypertensive crisis 0/868 (0%) 1/868 (0.1%)
    Venous thrombosis 1/868 (0.1%) 0/868 (0%)
    Venous thrombosis limb 0/868 (0%) 1/868 (0.1%)
    Other (Not Including Serious) Adverse Events
    BG00012 240 mg BID BG00012 240 mg TID
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 779/868 (89.7%) 767/868 (88.4%)
    Blood and lymphatic system disorders
    Lymphopenia 52/868 (6%) 42/868 (4.8%)
    Gastrointestinal disorders
    Abdominal pain 50/868 (5.8%) 55/868 (6.3%)
    Abdominal pain upper 69/868 (7.9%) 76/868 (8.8%)
    Diarrhoea 111/868 (12.8%) 118/868 (13.6%)
    Nausea 56/868 (6.5%) 61/868 (7%)
    Vomiting 42/868 (4.8%) 45/868 (5.2%)
    General disorders
    Fatigue 100/868 (11.5%) 102/868 (11.8%)
    Pyrexia 47/868 (5.4%) 43/868 (5%)
    Infections and infestations
    Bronchitis 82/868 (9.4%) 98/868 (11.3%)
    Gastroenteritis 52/868 (6%) 33/868 (3.8%)
    Herpes zoster 47/868 (5.4%) 38/868 (4.4%)
    Influenza 87/868 (10%) 67/868 (7.7%)
    Nasopharyngitis 220/868 (25.3%) 226/868 (26%)
    Pharyngitis 44/868 (5.1%) 50/868 (5.8%)
    Sinusitis 65/868 (7.5%) 63/868 (7.3%)
    Upper respiratory tract infection 143/868 (16.5%) 136/868 (15.7%)
    Urinary tract infection 196/868 (22.6%) 164/868 (18.9%)
    Injury, poisoning and procedural complications
    Fall 60/868 (6.9%) 63/868 (7.3%)
    Investigations
    Alanine aminotransferase increased 53/868 (6.1%) 59/868 (6.8%)
    Albumin urine present 66/868 (7.6%) 62/868 (7.1%)
    Lymphocyte count decreased 56/868 (6.5%) 42/868 (4.8%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 97/868 (11.2%) 115/868 (13.2%)
    Back pain 125/868 (14.4%) 125/868 (14.4%)
    Muscle spasms 38/868 (4.4%) 49/868 (5.6%)
    Musculoskeletal pain 35/868 (4%) 49/868 (5.6%)
    Pain in extremity 102/868 (11.8%) 92/868 (10.6%)
    Nervous system disorders
    Dizziness 60/868 (6.9%) 45/868 (5.2%)
    Headache 145/868 (16.7%) 131/868 (15.1%)
    Hypoaesthesia 64/868 (7.4%) 49/868 (5.6%)
    Multiple sclerosis relapse 324/868 (37.3%) 335/868 (38.6%)
    Paraesthesia 57/868 (6.6%) 59/868 (6.8%)
    Psychiatric disorders
    Anxiety 31/868 (3.6%) 46/868 (5.3%)
    Depression 102/868 (11.8%) 87/868 (10%)
    Insomnia 52/868 (6%) 51/868 (5.9%)
    Renal and urinary disorders
    Haematuria 49/868 (5.6%) 61/868 (7%)
    Microalbuminuria 55/868 (6.3%) 61/868 (7%)
    Proteinuria 76/868 (8.8%) 81/868 (9.3%)
    Respiratory, thoracic and mediastinal disorders
    Cough 54/868 (6.2%) 66/868 (7.6%)
    Skin and subcutaneous tissue disorders
    Erythema 47/868 (5.4%) 32/868 (3.7%)
    Pruritus 50/868 (5.8%) 38/868 (4.4%)
    Rash 45/868 (5.2%) 40/868 (4.6%)
    Vascular disorders
    Flushing 170/868 (19.6%) 165/868 (19%)
    Hot flush 44/868 (5.1%) 53/868 (6.1%)
    Hypertension 51/868 (5.9%) 43/868 (5%)

    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 US Biogen Clinical Trial Center
    Organization Biogen
    Phone 866-633-4636
    Email clinicaltrials@biogen.com
    Responsible Party:
    Biogen
    ClinicalTrials.gov Identifier:
    NCT00835770
    Other Study ID Numbers:
    • 109MS303
    • 2008-004753-14
    First Posted:
    Feb 4, 2009
    Last Update Posted:
    Dec 31, 2020
    Last Verified:
    Dec 1, 2020