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Efficacy and Safety of Oral BG00012 in Relapsing-Remitting Multiple Sclerosis (DEFINE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00420212
Recruitment Status : Completed
First Posted : January 11, 2007
Results First Posted : June 2, 2014
Last Update Posted : January 26, 2015
Sponsor:
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Relapsing-Remitting Multiple Sclerosis
Interventions Drug: BG00012
Drug: Placebo
Enrollment 1234
Recruitment Details Subjects were screened and enrolled at 198 investigational sites in 28 countries.
Pre-assignment Details From screening, 1237 eligible subjects were equally randomized. Of these, 1234 subjects received at least one dose of study treatment and comprised the intent-to-treat (ITT) and safety populations.
Arm/Group Title Placebo BG00012 240 mg Twice Daily (BID) BG00012 240 mg 3 Times Daily (TID)
Hide Arm/Group Description Participants received two placebo capsules orally three times daily (TID) Participants received two 120 mg BG00012 capsules orally twice daily (BID) and two placebo capsules orally once daily (QD) Participants received two 120 mg BG00012 capsules orally three times daily (TID)
Period Title: Overall Study
Started 408 [1] 410 [2] 416 [3]
Completed 317 315 320
Not Completed 91 95 96
Reason Not Completed
Adverse Event             22             40             36
Lost to Follow-up             9             11             11
Withdrawal by Subject             31             22             19
Physician Decision             4             4             3
Protocol Violation             4             4             8
Death             0             0             1
Other-Unspecified             21             14             18
[1]
408 participants were dosed; 410 participants were randomized
[2]
410 participants were dosed; 411 participants were randomized
[3]
416 participants were dosed; 416 participants were randomized
Arm/Group Title Placebo BG00012 240 mg Twice Daily (BID) BG00012 240 mg 3 Times Daily (TID) Total
Hide Arm/Group Description Participants received two placebo capsules orally three times daily (TID) Participants received two 120 mg BG00012 capsules orally twice daily (BID) and two placebo capsules orally once daily (QD) Participants received two 120 mg BG00012 capsules orally three times daily (TID) Total of all reporting groups
Overall Number of Baseline Participants 408 410 416 1234
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 408 participants 410 participants 416 participants 1234 participants
38.5  (9.14) 38.1  (9.11) 38.8  (8.85) 38.5  (9.03)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 408 participants 410 participants 416 participants 1234 participants
Female
306
  75.0%
296
  72.2%
306
  73.6%
908
  73.6%
Male
102
  25.0%
114
  27.8%
110
  26.4%
326
  26.4%
Mean Expanded Disability Status Scale (EDSS) score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 408 participants 410 participants 416 participants 1234 participants
2.48  (1.241) 2.40  (1.290) 2.36  (1.188) 2.42  (1.240)
[1]
Measure Description: The EDSS scores range from 0.0 (normal exam) to 10.0 (death due to MS).
Mean number of relapses within the previous 3 years  
Mean (Standard Deviation)
Unit of measure:  Number of relapses
Number Analyzed 408 participants 410 participants 416 participants 1234 participants
2.5  (1.56) 2.5  (1.44) 2.4  (1.27) 2.5  (1.43)
Mean number of relapses within the past 12 months  
Mean (Standard Deviation)
Unit of measure:  Number of relapses
Number Analyzed 408 participants 410 participants 416 participants 1234 participants
1.3  (0.67) 1.3  (0.67) 1.3  (0.60) 1.3  (0.65)
Time since first multiple sclerosis (MS) diagnosis  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 408 participants 410 participants 416 participants 1234 participants
5.8  (5.78) 5.6  (5.39) 5.1  (5.29) 5.5  (5.49)
Mean number of gadolinium (Gd) enhancing lesions   [1] 
Mean (Standard Deviation)
Unit of measure:  Number of Gd enhancing lesions
Number Analyzed 408 participants 410 participants 416 participants 1234 participants
1.6  (3.45) 1.2  (3.30) 1.2  (4.10) 1.4  (3.64)
[1]
Measure Description: This baseline measure could only be assessed in the magnetic resonance imaging (MRI) cohort. The MRI cohort included 540 intent-to-treat (ITT) subjects who were enrolled at sites that participated in the MRI portion of the study and who had MRI data (180 placebo, 176 BG00012 BID, 184 BG00012 TID). Sites could participate only if their MRI capability was validated by the independent MRI reading center. Approximately 95% of all subjects enrolled at MRI sites participated in the MRI portion of the study.
1.Primary Outcome
Title Proportion of Subjects Relapsed
Hide Description A protocol-defined relapse was defined as new or recurrent neurologic symptoms not associated with fever or infection that lasted at least 24 hours, and were separated by at least 30 days from onset of a preceding relapse. All protocol-defined relapses were evaluated by an independent neurolgic evaluation committee. The proportion of subjects with a relapse was estimated using the Kaplan-Meier method, which was based on the time-to-first-relapse survival distribution.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was based on the ITT population, defined as all subjects who were randomized and received at least 1 dose of study medication. Among subjects who switched to an alternative therapy for multiple sclerosis, all the data before the switch were used for the analysis. In all other subjects, all relapses were included in the analysis.
Arm/Group Title Placebo BG00012 240 mg Twice Daily (BID) BG00012 240 mg 3 Times Daily (TID)
Hide Arm/Group Description:
Participants received two placebo capsules orally three times daily (TID)
Participants received two 120 mg BG00012 capsules orally twice daily (BID) and two placebo capsules orally once daily (QD)
Participants received two 120 mg BG00012 capsules orally three times daily (TID)
Overall Number of Participants Analyzed 408 410 416
Measure Type: Number
Unit of Measure: Proportion of subjects,confirmed relapse
0.461 0.270 0.260
2.Secondary Outcome
Title Number of New or Newly Enlarging T2 Hyperintense Lesions
Hide Description The number of new or newly enlarging T2 hyperintense lesions at 2 years that developed in each subject compared to baseline assessed on brain magnetic resonance imaging (MRI) scans. The estimates of mean T2 lesion count were calculated from a negative binomial regression model adjusted for region and baselineT2 lesion volume
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 540 subjects included in the MRI cohort, 469 subjects (165 placebo, 152 BG00012 BID, 152 BG00012 TID) had post-baseline T2 data and were included in the analysis. Missing data before the use of alternative MS medications and visits after patients switched to alternative MS medications were imputed with the use of a constant rate assumption.
Arm/Group Title Placebo BG00012 240 mg BID BG00012 240 mg TID
Hide Arm/Group Description:
Participants received two placebo capsules orally three times daily (TID)
Participants received two 120 mg BG00012 capsules orally twice daily (BID) and two placebo capsules orally once daily (QD)
Participants received two 120 mg BG00012 capsules orally three times daily (TID)
Overall Number of Participants Analyzed 165 152 152
Mean (95% Confidence Interval)
Unit of Measure: Number of lesions
17.0
(12.9 to 22.4)
2.6
(2.0 to 3.5)
4.4
(3.2 to 5.9)
3.Secondary Outcome
Title Number of Gadolinium-enhancing T1-weighted Lesions
Hide Description The number of Gd-enhancing lesions was assessed using brain MRI scans following administration of gadolinium, a contrast agent. The mean number of Gd-enhancing lesions at 2 years was the average of the number of lesions at 2 years in a treatment group.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 540 subjects included in the MRI cohort, 469 (165 placebo,152 BG00012 BID,152 BG00012 TID) had post-baseline Gd-enhancing lesion data & were included in the analysis. Missing data before the use of alternative MS medications & visits after patients switched to alternative MS medications were imputed with the use of a constant rate assumption
Arm/Group Title Placebo BG00012 240 mg BID BG00012 240 mg TID
Hide Arm/Group Description:
Participants received two placebo capsules orally three times daily (TID)
Participants received two 120 mg BG00012 capsules orally twice daily (BID) and two placebo capsules orally once daily (QD)
Participants received two 120 mg BG00012 capsules orally three times daily (TID)
Overall Number of Participants Analyzed 165 152 152
Mean (Standard Deviation)
Unit of Measure: Number of lesions
1.8  (4.15) 0.1  (0.63) 0.5  (1.73)
4.Secondary Outcome
Title Number of Subjects With Gadolinium (Gd)-Enhancing Lesions
Hide Description Note: This outcome measure represents the categorical analysis for the previously listed secondary outcome measure "Number of Gadolinium-enhancing T1-weighted lesions"
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Of the 540 subjects included in the MRI cohort, 469 (165 placebo,152 BG00012 BID,152 BG00012 TID) had post-baseline Gd-enhancing lesion data & were included in the analysis. Missing data before the use of alternative MS medications & visits after patients switched to alternative MS medications were imputed with the use of a constant rate assumption
Arm/Group Title Placebo BG00012 240 mg Twice Daily (BID) BG00012 240 mg 3 Times Daily (TID)
Hide Arm/Group Description:
Participants received two placebo capsules orally three times daily (TID)
Participants received two 120 mg BG00012 capsules orally twice daily (BID) and two placebo capsules orally once daily (QD)
Participants received two 120 mg BG00012 capsules orally three times daily (TID)
Overall Number of Participants Analyzed 165 152 152
Measure Type: Number
Unit of Measure: Number of subjects
0 lesions 103 142 130
1 lesion 16 8 10
2 lesions 13 1 2
3-4 lesions 15 0 3
>=5 lesions 18 1 7
5.Secondary Outcome
Title Annualized Relapse Rate
Hide Description A protocol-defined relapse was defined as new or recurrent neurologic symptoms not associated with fever or infection that lasted at least 24 hours, and were separated by at least 30 days from onset of a preceding relapse. All protocol-defined relapses were evaluated by an independent neurologic evaluation committee. The adjusted annualized relapse rate was calculated from a negative binomial regression model, adjusted for baseline EDSS (≤ 2.0 vs. >2.0), age (<40 versus ≥40 years), region, and the number of relapses in the 1 year prior to enrollment.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population was defined as all subjects who were randomized and received at least 1 dose of study medication. Among subjects who switched to an alternative therapy for multiple sclerosis, all the data before the switch were used for the analysis. In all other subjects, all relapses were included in the analysis.
Arm/Group Title Placebo BG00012 240 mg BID BG00012 240 mg TID
Hide Arm/Group Description:
Participants received two placebo capsules orally three times daily (TID)
Participants received two 120 mg BG00012 capsules orally twice daily (BID) and two placebo capsules orally once daily (QD)
Participants received two 120 mg BG00012 capsules orally three times daily (TID)
Overall Number of Participants Analyzed 408 410 416
Mean (95% Confidence Interval)
Unit of Measure: Relapses per year
0.364
(0.303 to 0.436)
0.172
(0.138 to 0.214)
0.189
(0.153 to 0.234)
6.Secondary Outcome
Title Proportion of Subjects Experiencing Progression of Disability Assessed Using the Expanded Disability Status Scale (EDSS)
Hide Description The EDSS is based on a standardized neurological examination and focuses on symptoms that commonly occur in MS. EDSS scores range from 0.0 (normal) to 10.0 (death due to MS). Disability progression was defined as ≥ 1.0 point increase in subjects with a baseline EDSS of ≥1.0, or a ≥1.5 point increase in subjects with a baseline EDSS = 0, and required that the increase from baseline was confirmed ≥12 weeks later. The proportion of subjects with confirmed (12-week) disability progression was estimated using the Kaplan-Meier method, which was based on the time-to-first-progression survival distribution.
Time Frame 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population consisted of the ITT population (all subjects who were randomized and received at least 1 dose of study medication) who had a baseline EDSS assessment. Analysis were based on all observed data. Onset of disability progression must begin before a subject switched to alternative MS medication.
Arm/Group Title Placebo BG00012 240 mg BID BG00012 240 mg TID
Hide Arm/Group Description:
Participants received two placebo capsules orally three times daily (TID)
Participants received two 120 mg BG00012 capsules orally twice daily (BID) and two placebo capsules orally once daily (QD)
Participants received two 120 mg BG00012 capsules orally three times daily (TID)
Overall Number of Participants Analyzed 408 409 416
Measure Type: Number
Unit of Measure: Proportion of participants
0.271 0.164 0.177
Time Frame 2 years
Adverse Event Reporting Description The safety population consisted of all subjects who received at least 1 dose of study treatment. Safety data were analyzed by actual treatment received. Among subjects who switched to an alternative therapy for MS, all the data before the switch were used for the analysis. In all other subjects, all data were included in the analysis.
 
Arm/Group Title Placebo BG00012 240 mg Twice Daily (BID) BG00012 240 mg 3 Times Daily (TID) Total BG00012
Hide Arm/Group Description Participants received two placebo capsules orally three times daily (TID) Participants received two 120 mg BG00012 capsules orally twice daily (BID) and two placebo capsules orally once daily (QD) Participants received two 120 mg BG00012 capsules orally three times daily (TID) Combined BG00012 240 mg twice daily (BID) dose group and BG00012 240 mg 3 times daily (TID) dose group
All-Cause Mortality
Placebo BG00012 240 mg Twice Daily (BID) BG00012 240 mg 3 Times Daily (TID) Total BG00012
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo BG00012 240 mg Twice Daily (BID) BG00012 240 mg 3 Times Daily (TID) Total BG00012
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   86/408 (21.08%)   74/410 (18.05%)   65/416 (15.63%)   139/826 (16.83%) 
Blood and lymphatic system disorders         
Anaemia  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Microcytic Anaemia  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Cardiac disorders         
Acute Coronary Syndrome  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Cardiac Failure  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Cardiac Failure Congestive  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Congenital, familial and genetic disorders         
Hydrocele  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Ear and labyrinth disorders         
Vertigo Positional  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Endocrine disorders         
Goitre  1  0/408 (0.00%)  1/410 (0.24%)  2/416 (0.48%)  2/826 (0.24%) 
Endocrinopathy Diencephalic  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Gastrointestinal disorders         
Gastritis  1  0/408 (0.00%)  0/410 (0.00%)  3/416 (0.72%)  3/826 (0.36%) 
Vomiting  1  0/408 (0.00%)  1/410 (0.24%)  1/416 (0.24%)  2/826 (0.24%) 
Abdominal Hernia  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Abdominal Pain Lower  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Constipation  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Gastrontestinal Disorder  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Hiatus Hernia  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Colitis  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Colitis Ulcerative  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Gastrointestinal Haemorrhage  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Peritoneal Haemorrhage  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
General disorders         
Pyrexia  1  0/408 (0.00%)  1/410 (0.24%)  1/416 (0.24%)  2/826 (0.24%) 
Non-Cardiac Chest Pain  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Influenza Like Illness  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Pelvic Mass  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Hepatobiliary disorders         
Cholelithiasis  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Hepatitis Cholestatic  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Immune system disorders         
Hypersensitivity  1  0/408 (0.00%)  1/410 (0.24%)  1/416 (0.24%)  2/826 (0.24%) 
Anaphylactoid Reaction  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Infections and infestations         
Gastroenteritis  1  0/408 (0.00%)  4/410 (0.98%)  1/416 (0.24%)  5/826 (0.61%) 
Pneumonia  1  1/408 (0.25%)  2/410 (0.49%)  0/416 (0.00%)  2/826 (0.24%) 
Sinusitis  1  0/408 (0.00%)  1/410 (0.24%)  1/416 (0.24%)  2/826 (0.24%) 
Viral Infection  1  0/408 (0.00%)  1/410 (0.24%)  1/416 (0.24%)  2/826 (0.24%) 
Appendicitis  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
H1N1 Influenza  1  1/408 (0.25%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Influenza  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Peritonsillar Abscess  1  0/408 (0.00%)  0/410 (0.00%)  0/416 (0.00%)  1/826 (0.12%) 
Post Viral Fatigue Syndrome  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Urinary Tract Infection  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Vulval Abscess  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Anal Abscess  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Diarrhoea Infectious  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Nasopharyngitis  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Pelvic Inflammatory Disease  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Reiter's Syndrome  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Sepsis  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Tuberculosis Gastrointestinal  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Cellulitis  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Injury, poisoning and procedural complications         
Road Traffic Accident  1  0/408 (0.00%)  1/410 (0.24%)  1/416 (0.24%)  2/826 (0.24%) 
Ankle Fracture  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Concussion  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Meniscus Lesion  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Postoperative Fever  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Procedural Hypotension  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Radius Fracture  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Traumatic Brain Injury  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Wrist Fracture  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Femoral Neck Fracture  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Tendon Rupture  1  2/408 (0.49%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Tibia Fracture  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Investigations         
Allergy Test  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Blood Glucose Increased  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Colonoscopy  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Investigation  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Medical Observation  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Hepatic Enzyme Increased  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Metabolism and nutrition disorders         
Hypoglycaemia  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Musculoskeletal and connective tissue disorders         
Back Pain  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Sjogren's Syndrome  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Osteoarthritis  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Polyarthritis  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Synovial Cyst  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Benign Lung Neoplasm  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Breast Cancer  1  1/408 (0.25%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Cervix Carcinoma  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Neurilemmoma  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Transitional Cell Carcinoma  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Uterine Leiomyoma  1  2/408 (0.49%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Basal Cell Carcinoma  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Haemangioma  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Nervous system disorders         
Multiple Sclerosis Relapse  1  60/408 (14.71%)  39/410 (9.51%)  32/416 (7.69%)  71/826 (8.60%) 
Headache  1  0/408 (0.00%)  0/410 (0.00%)  2/416 (0.48%)  2/826 (0.24%) 
Neurological Symptom  1  0/408 (0.00%)  1/410 (0.24%)  1/416 (0.24%)  2/826 (0.24%) 
Altered State of Conciousness  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Epilepsy  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Glossopharyngeal Neuralgia  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Ischaemic Stroke  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Multiple Sclerosis  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Transient Global Amnesia  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Transient Ischaemic Attack  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Transverse Sinus Thrombosis  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Viith Nerve Paralysis  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Convulsion  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Encephalopathy  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Grand Mal Convulsion  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Loss of Conciousness  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Migraine  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Restless Legs Syndrome  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Psychiatric disorders         
Adjustment Disorder with Depressed Mood  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Depression  1  2/408 (0.49%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Generalized Anxiety Disorder  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Mania  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Narcissistic Personality Disorder  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Suicidal Ideation  1  1/408 (0.25%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Renal and urinary disorders         
Renal Colic  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Ureterocele  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Reproductive system and breast disorders         
Ovarian Cyst  1  1/408 (0.25%)  1/410 (0.24%)  2/416 (0.48%)  3/826 (0.36%) 
Adenomyosis  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Endometriosis  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Ovarian Cyst Ruptured  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Menstrual Disorder  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Pelvic Pain  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Uterine Haemorrhage  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Pleural Effusion  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Pneumonia Aspiration  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Skin and subcutaneous tissue disorders         
Pruritus  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Stevens-Johnson Syndrome  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Dermatitis Allergic  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Surgical and medical procedures         
Female Sterilization  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Hysterectomy  1  0/408 (0.00%)  1/410 (0.24%)  0/416 (0.00%)  1/826 (0.12%) 
Venous Stent Insertion  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Vascular disorders         
Flushing  1  0/408 (0.00%)  1/410 (0.24%)  1/416 (0.24%)  2/826 (0.24%) 
Varicose Vein  1  0/408 (0.00%)  1/410 (0.24%)  1/416 (0.24%)  2/826 (0.24%) 
Deep Vein Thrombosis  1  0/408 (0.00%)  0/410 (0.00%)  1/416 (0.24%)  1/826 (0.12%) 
Peripheral Ischaemia  1  1/408 (0.25%)  0/410 (0.00%)  0/416 (0.00%)  0/826 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 13.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo BG00012 240 mg Twice Daily (BID) BG00012 240 mg 3 Times Daily (TID) Total BG00012
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   384/408 (94.12%)   394/410 (96.10%)   393/416 (94.47%)   787/826 (95.28%) 
Ear and labyrinth disorders         
VERTIGO  1  15/408 (3.68%)  13/410 (3.17%)  29/416 (6.97%)  42/826 (5.08%) 
Gastrointestinal disorders         
DIARRHEA  1  55/408 (13.48%)  62/410 (15.12%)  78/416 (18.75%)  140/826 (16.95%) 
NAUSEA  1  38/408 (9.31%)  53/410 (12.93%)  54/416 (12.98%)  107/826 (12.95%) 
ABDOMINAL PAIN UPPER  1  28/408 (6.86%)  40/410 (9.76%)  52/416 (12.50%)  92/826 (11.14%) 
ABDOMINAL PAIN  1  22/408 (5.39%)  46/410 (11.22%)  37/416 (8.89%)  83/826 (10.05%) 
VOMITING  1  24/408 (5.88%)  40/410 (9.76%)  29/416 (6.97%)  69/826 (8.35%) 
DYSPEPSIA  1  12/408 (2.94%)  23/410 (5.61%)  24/416 (5.77%)  47/826 (5.69%) 
CONSTIPATION  1  19/408 (4.66%)  14/410 (3.41%)  18/416 (4.33%)  32/826 (3.87%) 
GASTROINTESTINAL DISORDER  1  6/408 (1.47%)  9/410 (2.20%)  20/416 (4.81%)  29/826 (3.51%) 
General disorders         
FATIGUE  1  54/408 (13.24%)  57/410 (13.90%)  63/416 (15.14%)  120/826 (14.53%) 
PYREXIA  1  21/408 (5.15%)  16/410 (3.90%)  18/416 (4.33%)  34/826 (4.12%) 
Infections and infestations         
NASOPHARYNGITIS  1  101/408 (24.75%)  108/410 (26.34%)  109/416 (26.20%)  217/826 (26.27%) 
UPPER RESPIRATORY TRACT INFECTION  1  53/408 (12.99%)  63/410 (15.37%)  51/416 (12.26%)  114/826 (13.80%) 
URINARY TRACT INFECTION  1  53/408 (12.99%)  55/410 (13.41%)  54/416 (12.98%)  109/826 (13.20%) 
INFLUENZA  1  39/408 (9.56%)  34/410 (8.29%)  48/416 (11.54%)  82/826 (9.93%) 
SINUSITIS  1  20/408 (4.90%)  17/410 (4.15%)  34/416 (8.17%)  51/826 (6.17%) 
BRONCHITIS  1  18/408 (4.41%)  21/410 (5.12%)  26/416 (6.25%)  47/826 (5.69%) 
GASTROENTERITIS  1  21/408 (5.15%)  26/410 (6.34%)  20/416 (4.81%)  46/826 (5.57%) 
RHINITIS  1  19/408 (4.66%)  12/410 (2.93%)  16/416 (3.85%)  28/826 (3.39%) 
Investigations         
ALANINE AMINOTRANSFERASE INCREASED  1  13/408 (3.19%)  29/410 (7.07%)  27/416 (6.49%)  56/826 (6.78%) 
ALBUMIN URINE PRESENT  1  12/408 (2.94%)  24/410 (5.85%)  22/416 (5.29%)  46/826 (5.57%) 
Musculoskeletal and connective tissue disorders         
BACK PAIN  1  57/408 (13.97%)  59/410 (14.39%)  46/416 (11.06%)  105/826 (12.71%) 
ARTHRALGIA  1  39/408 (9.56%)  46/410 (11.22%)  37/416 (8.89%)  83/826 (10.05%) 
PAIN IN EXTREMITY  1  29/408 (7.11%)  37/410 (9.02%)  29/416 (6.97%)  66/826 (7.99%) 
MUSCLE SPASMS  1  20/408 (4.90%)  13/410 (3.17%)  27/416 (6.49%)  40/826 (4.84%) 
MUSCULAR WEAKNESS  1  26/408 (6.37%)  12/410 (2.93%)  14/416 (3.37%)  26/826 (3.15%) 
MUSCULOSKELETAL PAIN  1  21/408 (5.15%)  11/410 (2.68%)  10/416 (2.40%)  21/826 (2.54%) 
Nervous system disorders         
MULTIPLE SCLEROSIS RELAPSE  1  181/408 (44.36%)  109/410 (26.59%)  107/416 (25.72%)  216/826 (26.15%) 
HEADACHE  1  80/408 (19.61%)  81/410 (19.76%)  78/416 (18.75%)  159/826 (19.25%) 
PARAESTHESIA  1  38/408 (9.31%)  35/410 (8.54%)  38/416 (9.13%)  73/826 (8.84%) 
HYPOAESTHESIA  1  27/408 (6.62%)  20/410 (4.88%)  24/416 (5.77%)  44/826 (5.33%) 
DIZZINESS  1  23/408 (5.64%)  19/410 (4.63%)  22/416 (5.29%)  41/826 (4.96%) 
Psychiatric disorders         
DEPRESSION  1  32/408 (7.84%)  29/410 (7.07%)  33/416 (7.93%)  62/826 (7.51%) 
INSOMNIA  1  19/408 (4.66%)  20/410 (4.88%)  20/416 (4.81%)  40/826 (4.84%) 
Renal and urinary disorders         
PROTEINURIA  1  34/408 (8.33%)  38/410 (9.27%)  50/416 (12.02%)  88/826 (10.65%) 
HAEMATURIA  1  19/408 (4.66%)  26/410 (6.34%)  26/416 (6.25%)  52/826 (6.30%) 
MICROALBUMINURIA  1  11/408 (2.70%)  21/410 (5.12%)  17/416 (4.09%)  38/826 (4.60%) 
Respiratory, thoracic and mediastinal disorders         
OROPHARYNGEAL PAIN  1  19/408 (4.66%)  25/410 (6.10%)  21/416 (5.05%)  46/826 (5.57%) 
COUGH  1  18/408 (4.41%)  22/410 (5.37%)  19/416 (4.57%)  41/826 (4.96%) 
Skin and subcutaneous tissue disorders         
PRURITIS  1  19/408 (4.66%)  42/410 (10.24%)  33/416 (7.93%)  75/826 (9.08%) 
RASH  1  13/408 (3.19%)  34/410 (8.29%)  27/416 (6.49%)  61/826 (7.38%) 
ERYTHEMA  1  5/408 (1.23%)  20/410 (4.88%)  33/416 (7.93%)  53/826 (6.42%) 
Vascular disorders         
FLUSHING  1  20/408 (4.90%)  153/410 (37.32%)  132/416 (31.73%)  285/826 (34.50%) 
HOT FLUSH  1  8/408 (1.96%)  31/410 (7.56%)  29/416 (6.97%)  60/826 (7.26%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The provisions of the agreements are 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 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
Layout table for Results Point of Contact information
Name/Title: Biogen Idec Study Medical Director
Organization: Biogen Idec
EMail: clinicaltrials@biogenidec.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT00420212    
Other Study ID Numbers: 109MS301
First Submitted: January 8, 2007
First Posted: January 11, 2007
Results First Submitted: May 5, 2014
Results First Posted: June 2, 2014
Last Update Posted: January 26, 2015