Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Long Term Safety and Efficacy Study of Teriflunomide 7 mg or 14 mg in Patients With Relapsing-Remitting Multiple Sclerosis

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: NCT00803049
Recruitment Status : Completed
First Posted : December 5, 2008
Results First Posted : January 30, 2017
Last Update Posted : January 30, 2017
Sponsor:
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Multiple Sclerosis
Intervention Drug: Teriflunomide (HMR1726)
Enrollment 742
Recruitment Details The study was conducted at 117 centres in 21 countries between 16 October 2006 and 23 December 2015. A total of 742 participants who completed study EFC6049 (NCT00134563), entered in this extension study (LTS6050 [NCT00803049]).
Pre-assignment Details Participants who received placebo in EFC6049 study were randomized in 1:1 ratio to receive either teriflunomide 7 mg/day or 14 mg/day and, those who received teriflunomide 7 mg/day or 14 mg/day in EFC6049 (NCT00134563) received same double-blind treatment in this extension study.
Arm/Group Title Placebo/Teriflunomide 7 mg Teriflunomide 7 mg/7 mg Placebo/Teriflunomide 14 mg Teriflunomide 14 mg/14 mg
Hide Arm/Group Description Participants who completed treatment of placebo (for teriflunomide) tablet once daily (QD) for 108 weeks in EFC6049 study, received teriflunomide tablet 7 mg QD for 288 weeks in this extension study. Participants who completed treatment of teriflunomide 7 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 7 mg tablet QD for 288 weeks in this extension study. Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049, study received teriflunomide 14 mg tablet QD for 288 weeks in this extension study. Participants who completed treatment of teriflunomide 14 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Period Title: Overall Study
Started 129 [1] 252 [1] 108 [1] 253 [1]
Treated 129 252 108 251
Safety Population 129 254 [2] 107 [3] 250 [3]
Completed 68 134 64 151
Not Completed 61 118 44 102
Reason Not Completed
Adverse Event             21             33             13             27
Lack of Efficacy             10             19             6             13
Lost to Follow-up             0             2             0             3
Death             2             1             0             2
Progressive Disease             6             10             6             6
Withdrawal by Subject             19             43             16             44
Protocol Violation             0             1             1             0
Randomized and Not Treated             0             0             0             2
Other than Specified Above             3             9             2             5
[1]
Randomized in extension study
[2]
Included 1 participant from Placebo/Teriflunomide 14 mg and 1 from Teriflunomide14 mg/14 mg arm
[3]
1 participant received Teriflunomide 7 mg and analysed in Teriflunomide 7 mg/7 mg arm
Arm/Group Title Placebo/Teriflunomide 7 mg Teriflunomide 7 mg/7 mg Placebo/Teriflunomide 14 mg Teriflunomide 14 mg/14 mg Total
Hide Arm/Group Description Participants who completed treatment of placebo (for teriflunomide) tablet once daily (QD) for 108 weeks in EFC6049 study, received teriflunomide tablet 7 mg QD for 288 weeks in this extension study. Participants who completed treatment of teriflunomide 7 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 7 mg tablet QD for 288 weeks in this extension study. Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049, study received teriflunomide 14 mg tablet QD for 288 weeks in this extension study. Participants who completed treatment of teriflunomide 14 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 14 mg tablet QD for 288 weeks in this extension study. Total of all reporting groups
Overall Number of Baseline Participants 129 252 108 253 742
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 129 participants 252 participants 108 participants 253 participants 742 participants
39.6  (8.5) 38.0  (8.8) 37.6  (8.5) 38.6  (8.4) 38.4  (8.6)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 129 participants 252 participants 108 participants 253 participants 742 participants
Female
94
  72.9%
175
  69.4%
85
  78.7%
182
  71.9%
536
  72.2%
Male
35
  27.1%
77
  30.6%
23
  21.3%
71
  28.1%
206
  27.8%
1.Primary Outcome
Title Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
Hide Description Adverse event (AE) was defined as any untoward medical occurrence in a participant who received investigational medicinal product (IMP) without regard to possibility of causal relationship with this treatment. TEAEs: AEs that developed or worsened or became serious during on-treatment period which was defined as the period from the time of first dose of study drug (in LTS6050) up to 4 weeks (28 days) after last dose of study drug. Serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included both serious and non-serious AEs.
Time Frame Baseline (LTS6050) up to 28 days after last dose of study drug up to 450 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: all participants randomized in the LTS6050 study and exposed to IMP during the LTS6050 study treatment period, regardless of the amount of treatment administered. The safety analysis was conducted as the treatment received.
Arm/Group Title Placebo/Teriflunomide 7 mg Teriflunomide 7 mg/7 mg Placebo/Teriflunomide 14 mg Teriflunomide 14 mg/14 mg
Hide Arm/Group Description:
Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049 study, received teriflunomide tablet 7 mg QD for 288 weeks in this extension study.
Participants who completed treatment of teriflunomide 7 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 7 mg tablet QD for 288 weeks in this extension study.
Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049, study received teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Participants who completed treatment of teriflunomide 14 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Overall Number of Participants Analyzed 129 254 107 250
Measure Type: Number
Unit of Measure: percentage of participants
Any TEAE 93.8 91.3 94.4 91.2
Any Treatment Emergent SAE 24.8 28.0 21.5 24.8
Any TEAE Leading to Death 2.3 0.8 0 0.8
Any TEAE Leading to Permanent Discontinuation 17.1 12.2 12.1 10.8
2.Secondary Outcome
Title Time to 12 Week Sustained Disability Progression (DP): Kaplan-Meier Estimates of the Rate of DP
Hide Description Sustained DP defined as sustained increase of at least 1 point from baseline (EFC6049) expanded disability status scale (EDSS) score (0.5 point for participants with baseline EDSS>5.5) persisting for at least 12 weeks. EDSS: an ordinal scale qualifies disability in participants with MS. EDSS total score range: 0 (normal neurological examination) to 10 (death due to Multiple Sclerosis [MS]). Probability of DP at 12 weeks was estimated using Kaplan-Meier method on time to DP defined as date of first DP minus (-) date of randomization in EFC6049 study +1 day. Participants free of DP (no DP observed on treatment) were censored at the date of last on-treatment EDSS evaluation in LTS6050. Kaplan-Meier method consists in computing probabilities of non-occurrence of event at any observed time of event and multiplying successive probabilities for time ≤t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t.
Time Frame Up to 10.8 years (EFC6049: 108 weeks + LTS6050: 450 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) (EFC6049+ LTS6050) population: all participants randomized in both EFC6049 and LTS6050 studies that had at least 1-day IMP exposure during both EFC6049 and LTS6050 studies. Analysis for this outcome measure was performed on the combined data of EFC6049 andLTS6050 study, as pre-specified in the protocol.
Arm/Group Title Placebo/Teriflunomide 7 mg Teriflunomide 7 mg/7 mg Placebo/Teriflunomide 14 mg Teriflunomide 14 mg/14 mg
Hide Arm/Group Description:
Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049 study, received teriflunomide tablet 7 mg QD for 288 weeks in this extension study.
Participants who completed treatment of teriflunomide 7 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 7 mg tablet QD for 288 weeks in this extension study.
Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049, study received teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Participants who completed treatment of teriflunomide 14 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Overall Number of Participants Analyzed 129 252 108 251
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability
0.544
(0.441 to 0.646)
0.494
(0.423 to 0.565)
0.627
(0.444 to 0.811)
0.473
(0.403 to 0.543)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Teriflunomide 7 mg, Teriflunomide 7 mg/7 mg
Comments Analysis was performed using Log-rank test with treatment, EDSS strata at baseline and region as covariates. Estimation was performed using Cox proportional hazard model with treatment, EDSS strata at baseline and region as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2079
Comments Threshold for significance at 0.05 level.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.824
Confidence Interval (2-Sided) 95%
0.602 to 1.128
Estimation Comments Placebo/Teriflunomide 7 mg vs. Teriflunomide 7 mg/7 mg
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Teriflunomide 14 mg, Teriflunomide 14 mg/14 mg
Comments Analysis was performed using Log-rank test with treatment, EDSS strata at baseline and region as covariates. Estimation was performed using Cox proportional hazard model with treatment, EDSS strata at baseline and region as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3039
Comments Threshold for significance at 0.05 level.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.825
Confidence Interval (2-Sided) 95%
0.591 to 1.152
Estimation Comments Placebo/Teriflunomide 14 mg vs.Teriflunomide 14 mg/14 mg
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriflunomide 7 mg/7 mg, Teriflunomide 14 mg/14 mg
Comments Analysis was performed using Log-rank test with treatment, EDSS strata at baseline and region as covariates. Estimation was performed using Cox proportional hazard model with treatment, EDSS strata at baseline and region as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8271
Comments Threshold for significance at 0.05 level.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.963
Confidence Interval (2-Sided) 95%
0.736 to 1.260
Estimation Comments Teriflunomide 7 mg/7 mg vs. Teriflunomide 14 mg/14 mg
3.Secondary Outcome
Title Time to 24 Week Sustained Disability Progression (DP): Kaplan-Meier Estimates of the Rate of DP
Hide Description Sustained DP was defined as sustained increase of at least 1 point from baseline (EFC6049) EDSS score (0.5 point for participants with baseline EDSS>5.5) persisting for at least 24 weeks. EDSS: an ordinal scale qualifies disability in participants with MS. EDSS total score range: 0 (normal neurological examination) to 10 (death due to MS). Probability of DP at 24 weeks was estimated using Kaplan-Meier method on time to DP defined as date of first DP minus (-) date of randomization in EFC6049 study +1 day. Participants free of DP (no DP observed on treatment) were censored at the date of last on-treatment EDSS evaluation in LTS6050. Kaplan-Meier method consists in computing probabilities of non-occurrence of event at any observed time of event and multiplying successive probabilities for time ≤t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t.
Time Frame Up to 10.8 years (EFC6049: 108 weeks + LTS6050: 450 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) (EFC6049+ LTS6050) population: all participants randomized in both EFC6049 and LTS6050 studies that had at least 1-day IMP exposure during both EFC6049 and LTS6050 studies. Analysis for this outcome measure was performed on the combined data of EFC6049 andLTS6050 study, as pre-specified in the protocol.
Arm/Group Title Placebo/Teriflunomide 7 mg Teriflunomide 7 mg/7 mg Placebo/Teriflunomide 14 mg Teriflunomide 14 mg/14 mg
Hide Arm/Group Description:
Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049 study, received teriflunomide tablet 7 mg QD for 288 weeks in this extension study.
Participants who completed treatment of teriflunomide 7 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 7 mg tablet QD for 288 weeks in this extension study.
Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049, study received teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Participants who completed treatment of teriflunomide 14 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Overall Number of Participants Analyzed 129 252 108 251
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability
0.444
(0.338 to 0.550)
0.434
(0.363 to 0.504)
0.518
(0.411 to 0.624)
0.438
(0.367 to 0.509)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Teriflunomide 7 mg, Teriflunomide 7 mg/7 mg
Comments Analysis was performed using Log-rank test with treatment, EDSS strata at baseline and region as covariates. Estimation was performed using Cox proportional hazard model with treatment, EDSS strata at baseline and region as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8017
Comments Threshold for significance at 0.05 level.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.961
Confidence Interval (2-Sided) 95%
0.678 to 1.362
Estimation Comments Placebo/Teriflunomide 7 mg vs. Teriflunomide 7 mg/7 mg
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Teriflunomide 14 mg, Teriflunomide 14 mg/14 mg
Comments Analysis was performed using Log-rank test with treatment, EDSS strata at baseline and region as covariates. Estimation was performed using Cox proportional hazard model with treatment, EDSS strata at baseline and region as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1866
Comments Threshold for significance at 0.05 level.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.790
Confidence Interval (2-Sided) 95%
0.559 to 1.117
Estimation Comments Placebo/Teriflunomide 14 mg vs. Teriflunomide 14 mg/14 mg
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Teriflunomide 7 mg/7 mg, Teriflunomide 14 mg/14 mg
Comments Analysis was performed using Log-rank test with treatment, EDSS strata at baseline and region as covariates. Estimation was performed using Cox proportional hazard model with treatment, EDSS strata at baseline and region as covariates.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8763
Comments Threshold for significance at 0.05 level.
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.020
Confidence Interval (2-Sided) 95%
0.767 to 1.357
Estimation Comments Teriflunomide 7 mg/7 mg vs. Teriflunomide 14 mg/14 mg
4.Secondary Outcome
Title Percentage of Participants Free of Sustained Disability Progression (DP)
Hide Description Sustained DP was defined as sustained increase of at least 1 point from baseline (EFC6049) EDSS score (0.5 point for participants with baseline EDSS>5.5) persisting for at least 12 weeks and 24 weeks. EDSS is an ordinal scale in half-point increments that qualifies disability in participants with MS. It consists of 8 ordinal rating scales assessing seven functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder, cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicates worse neurological function. Percentage of participants who were considered as free of disability progression confirmed after 12 week sustained progression and 24 week sustained progression were reported. Analysis for this outcome measure was performed on combined data of EFC6049 and LTS6050 study, as pre-specified in protocol.
Time Frame Up to 10.8 years since EFC6049 randomization (EFC6049: 108 weeks + LTS6050: 450 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) (EFC6049 [NCT00134563] + LTS6050) population.
Arm/Group Title Placebo/Teriflunomide 7 mg Teriflunomide 7 mg/7 mg Placebo/Teriflunomide 14 mg Teriflunomide 14 mg/14 mg
Hide Arm/Group Description:
Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049 study, received teriflunomide tablet 7 mg QD for 288 weeks in this extension study.
Participants who completed treatment of teriflunomide 7 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 7 mg tablet QD for 288 weeks in this extension study.
Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049, study received teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Participants who completed treatment of teriflunomide 14 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Overall Number of Participants Analyzed 129 252 108 251
Measure Type: Number
Unit of Measure: percentage of participants
Free of DP Sustained for 12 Weeks 45.6 50.6 37.3 52.7
Free of DP Sustained for 24 Weeks 55.6 56.6 48.2 56.2
5.Secondary Outcome
Title Annualized MS Relapse Rate (ARR): Poisson Regression Estimates
Hide Description ARR was obtained from total number of confirmed relapses that occurred during treatment period divided by sum of treatment durations in LTS6050 study only. Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever was to be confirmed by an increase in EDSS score or Functional System (FS) scores. EDSS: an ordinal scale qualifies disability. EDSS total score range: 0 (normal neurological examination) to 10 (death due to MS). FSS: to assess the neurological function. Total score range: 0 (normal) - 6(worse), higher scores = worse neurological function. To account for the different treatment duration among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log transformed treatment duration as "offset" variable; treatment group, region of enrolment and baseline EDSS stratum as covariates).
Time Frame Up to 8 years since LTS6050 randomization
Hide Outcome Measure Data
Hide Analysis Population Description
ITT(LTS6050) population: all participants who were randomized in the LTS6050 study and had at least 1-day IMP exposure during the LTS6050 study.
Arm/Group Title Placebo/Teriflunomide 7 mg Teriflunomide 7 mg/7 mg Placebo/Teriflunomide 14 mg Teriflunomide 14 mg/14 mg
Hide Arm/Group Description:
Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049 study, received teriflunomide tablet 7 mg QD for 288 weeks in this extension study.
Participants who completed treatment of teriflunomide 7 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 7 mg tablet QD for 288 weeks in this extension study.
Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049, study received teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Participants who completed treatment of teriflunomide 14 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Overall Number of Participants Analyzed 129 252 108 251
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: relapses per participant-year
0.216
(0.162 to 0.288)
0.183
(0.149 to 0.225)
0.176
(0.132 to 0.236)
0.160
(0.129 to 0.198)
6.Secondary Outcome
Title Magnetic Resonance Imaging (MRI) Assessment: Change From Baseline in Total Volume of Abnormal Lesions (Burden of Disease [BOD]) at Week 192 Since LTS6050 Randomization
Hide Description BOD was assessed by cerebral MRI and defined as the total volume of all abnormal brain tissue (calculated as the sum of the total volume of T2-lesion component and T1-hypointense lesion component).
Time Frame Baseline, Week 192
Hide Outcome Measure Data
Hide Analysis Population Description
ITT (LTS6050 population). Number of participants analyzed=participants with available data for this outcome measure.
Arm/Group Title Placebo/Teriflunomide 7 mg Teriflunomide 7 mg/7 mg Placebo/Teriflunomide 14 mg Teriflunomide 14 mg/14 mg
Hide Arm/Group Description:
Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049 study, received teriflunomide tablet 7 mg QD for 288 weeks in this extension study.
Participants who completed treatment of teriflunomide 7 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 7 mg tablet QD for 288 weeks in this extension study.
Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049, study received teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Participants who completed treatment of teriflunomide 14 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Overall Number of Participants Analyzed 49 99 36 103
Mean (Standard Deviation)
Unit of Measure: millilitres (ml)
5.307  (9.088) 3.969  (11.135) 3.720  (6.696) 3.943  (9.685)
Time Frame All AEs were collected from signature of informed consent form up to 28 days after the last dose of study drug up to Week 450, regardless of seriousness or relationship to investigational product
Adverse Event Reporting Description Reported AEs are TEAEs that is AEs that developed/worsened during the 'on treatment period' (the time from the first dose of study treatment up to 4 weeks [28 days] after the last dose of study treatment). Analysis was performed on safety population and was conducted as per the treatment received.
 
Arm/Group Title Placebo/Teriflunomide 7 mg Teriflunomide 7 mg/7 mg Placebo/Teriflunomide 14 mg Teriflunomide 14 mg/14 mg
Hide Arm/Group Description Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049 study, received teriflunomide tablet 7 mg QD for 288 weeks in this extension study.

Participants who completed treatment of teriflunomide 7 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 7 mg tablet QD for 288 weeks in this extension study.

Included 2 participants randomized in placebo and teriflunomide 14 mg arm respectively in EFC6049 study, incorrectly received at least 1 dose of teriflunomide 7 mg. In LTS6050 study, same participants received correct dose of teriflunomide 14 mg but included in Teriflunomide 7mg/7 mg arm for safety analysis.

Participants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049, study received teriflunomide 14 mg tablet QD for 288 weeks in this extension study.

Excluded 1 participant randomized in placebo arm in EFC6049 study, incorrectly received at least 1 dose of teriflunomide 7 mg. In LTS6050 study, same participant received 14 mg dose but included in teriflunomide 7 mg/7 mg arm for safety analysis.

Participants who completed treatment of teriflunomide 14 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 14 mg tablet QD for 288 weeks in this extension study.

Excluded 1 participant randomized in 14 mg arm in EFC6049 study, incorrectly received at least 1 dose of teriflunomide 7 mg. In LTS6050 study, same participant received correct dose of 14 mg but included in Teriflunomide 7mg/7 mg arm for safety analysis.

All-Cause Mortality
Placebo/Teriflunomide 7 mg Teriflunomide 7 mg/7 mg Placebo/Teriflunomide 14 mg Teriflunomide 14 mg/14 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Hide Serious Adverse Events
Placebo/Teriflunomide 7 mg Teriflunomide 7 mg/7 mg Placebo/Teriflunomide 14 mg Teriflunomide 14 mg/14 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   32/129 (24.81%)   71/254 (27.95%)   23/107 (21.50%)   62/250 (24.80%) 
Blood and lymphatic system disorders         
Neutropenia  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Anaemia  1  0/129 (0.00%)  2/254 (0.79%)  0/107 (0.00%)  0/250 (0.00%) 
Cardiac disorders         
Myocardial infarction  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  3/250 (1.20%) 
Acute myocardial infarction  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Angina pectoris  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Arteriosclerosis coronary artery  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Bradycardia  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Cardiac failure acute  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Coronary artery disease  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Cardiac arrest  1  2/129 (1.55%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Cardiac valve disease  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Supraventricular tachycardia  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Congenital, familial and genetic disorders         
Dolichocolon  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Ear and labyrinth disorders         
Vertigo  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  1/250 (0.40%) 
Endocrine disorders         
Thyroiditis  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Eye disorders         
Uveitis  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Cystoid macular oedema  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Retinal detachment  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Gastrointestinal disorders         
Abdominal pain  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  2/250 (0.80%) 
Inguinal hernia  1  0/129 (0.00%)  2/254 (0.79%)  0/107 (0.00%)  2/250 (0.80%) 
Anal fissure  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Anal fistula  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Crohn's disease  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Diarrhoea  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  1/250 (0.40%) 
Diverticulum intestinal  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Gastrointestinal ulcer haemorrhage  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Large intestine perforation  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Mechanical ileus  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Abdominal pain upper  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Colitis microscopic  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Gastric ulcer haemorrhage  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Gastroduodenal haemorrhage  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Haemorrhoidal haemorrhage  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Hernial eventration  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Mesenteric haematoma  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Mouth swelling  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Volvulus  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
General disorders         
Pyrexia  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  2/250 (0.80%) 
Chest pain  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Adverse drug reaction  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Death  1  1/129 (0.78%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
General physical health deterioration  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Sudden death  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Hepatobiliary disorders         
Cholelithiasis  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  2/250 (0.80%) 
Cholecystitis chronic  1  1/129 (0.78%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Hepatic steatosis  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Hepatocellular injury  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Hepatotoxicity  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Infections and infestations         
Erysipelas  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  2/250 (0.80%) 
Urinary tract infection  1  1/129 (0.78%)  1/254 (0.39%)  0/107 (0.00%)  2/250 (0.80%) 
Anal abscess  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Appendicitis  1  0/129 (0.00%)  2/254 (0.79%)  0/107 (0.00%)  1/250 (0.40%) 
Cellulitis  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Clostridium difficile colitis  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Endometritis  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Gastrointestinal infection  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Hepatitis A  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Perirectal abscess  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  1/250 (0.40%) 
Pneumonia  1  0/129 (0.00%)  2/254 (0.79%)  0/107 (0.00%)  1/250 (0.40%) 
Pneumonia streptococcal  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Respiratory tract infection  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Sepsis  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  1/250 (0.40%) 
Subcutaneous abscess  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  1/250 (0.40%) 
Urosepsis  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  1/250 (0.40%) 
Vestibular neuronitis  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Bone abscess  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Bronchitis  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Bursitis infective  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Diverticulitis  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Gastroenteritis  1  0/129 (0.00%)  2/254 (0.79%)  0/107 (0.00%)  0/250 (0.00%) 
Infected dermal cyst  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Oral herpes  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Peritonitis  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Pneumonia bacterial  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Postoperative wound infection  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Pyelonephritis  1  2/129 (1.55%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Tooth abscess  1  1/129 (0.78%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Tubo-ovarian abscess  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Wound infection  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Injury, poisoning and procedural complications         
Hand fracture  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  2/250 (0.80%) 
Accidental overdose  1  1/129 (0.78%)  0/254 (0.00%)  1/107 (0.93%)  1/250 (0.40%) 
Ankle fracture  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  1/250 (0.40%) 
Cervical vertebral fracture  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Fall  1  1/129 (0.78%)  2/254 (0.79%)  0/107 (0.00%)  1/250 (0.40%) 
Femoral neck fracture  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Ligament rupture  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Road traffic accident  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Anastomotic leak  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Concussion  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Fibula fracture  1  1/129 (0.78%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Head injury  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Hepatic rupture  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Hip fracture  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Joint dislocation  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Ligament sprain  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Lower limb fracture  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Meniscus injury  1  1/129 (0.78%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Multiple fractures  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Patella fracture  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Procedural pain  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Radius fracture  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Rib fracture  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Tibia fracture  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Traumatic shock  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Wrist fracture  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Investigations         
Alanine aminotransferase increased  1  4/129 (3.10%)  3/254 (1.18%)  3/107 (2.80%)  6/250 (2.40%) 
Hepatic enzyme increased  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  2/250 (0.80%) 
Transaminases increased  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Aspartate aminotransferase increased  1  1/129 (0.78%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Blood alkaline phosphatase increased  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Blood pressure increased  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Gamma-glutamyltransferase increased  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Lipase increased  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Metabolism and nutrition disorders         
Diabetes mellitus inadequate control  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Diabetes mellitus  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Type 2 diabetes mellitus  1  0/129 (0.00%)  1/254 (0.39%)  1/107 (0.93%)  0/250 (0.00%) 
Musculoskeletal and connective tissue disorders         
Intervertebral disc protrusion  1  2/129 (1.55%)  5/254 (1.97%)  0/107 (0.00%)  2/250 (0.80%) 
Osteoarthritis  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Rotator cuff syndrome  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Arthralgia  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Arthropathy  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Back pain  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Bone cyst  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Lumbar spinal stenosis  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Osteonecrosis  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Tenosynovitis  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Meningioma  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Thyroid neoplasm  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Uterine leiomyoma  1  1/129 (0.78%)  0/254 (0.00%)  2/107 (1.87%)  1/250 (0.40%) 
Basal cell carcinoma  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Breast cancer  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Cholesteatoma  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Colon cancer metastatic  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Malignant melanoma  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Squamous cell carcinoma of the cervix  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Nervous system disorders         
Cerebrovascular accident  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Epilepsy  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Headache  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Paraplegia  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Seizure  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Syncope  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  1/250 (0.40%) 
Uhthoff's phenomenon  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Ageusia  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Carpal tunnel syndrome  1  0/129 (0.00%)  1/254 (0.39%)  1/107 (0.93%)  0/250 (0.00%) 
Cerebrovascular insufficiency  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Facial neuralgia  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Intracranial aneurysm  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Muscle spasticity  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Posterior reversible encephalopathy syndrome  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Sciatica  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Transient ischaemic attack  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Pregnancy, puerperium and perinatal conditions         
Abortion spontaneous  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Psychiatric disorders         
Suicidal ideation  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  2/250 (0.80%) 
Depression  1  1/129 (0.78%)  1/254 (0.39%)  0/107 (0.00%)  1/250 (0.40%) 
Suicide attempt  1  1/129 (0.78%)  0/254 (0.00%)  1/107 (0.93%)  1/250 (0.40%) 
Affective disorder  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Bipolar disorder  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Renal and urinary disorders         
Acute kidney injury  1  0/129 (0.00%)  1/254 (0.39%)  1/107 (0.93%)  0/250 (0.00%) 
Bladder prolapse  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Nephrolithiasis  1  1/129 (0.78%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Renal mass  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Urinary retention  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Reproductive system and breast disorders         
Endometriosis  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  2/250 (0.80%) 
Breast hyperplasia  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Menorrhagia  1  0/129 (0.00%)  2/254 (0.79%)  0/107 (0.00%)  1/250 (0.40%) 
Uterine haemorrhage  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Breast cyst  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Cervical polyp  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Metrorrhagia  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Ovarian cyst  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Premenstrual cramps  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Uterine polyp  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Nasal septum deviation  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Pulmonary embolism  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  1/250 (0.40%) 
Epistaxis  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Interstitial lung disease  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Skin and subcutaneous tissue disorders         
Alopecia areata  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Decubitus ulcer  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Lichen planus  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Pustular psoriasis  1  0/129 (0.00%)  0/254 (0.00%)  1/107 (0.93%)  0/250 (0.00%) 
Social circumstances         
Miscarriage of partner  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Surgical and medical procedures         
Mammoplasty  1  0/129 (0.00%)  0/254 (0.00%)  0/107 (0.00%)  1/250 (0.40%) 
Osteotomy  1  1/129 (0.78%)  0/254 (0.00%)  0/107 (0.00%)  0/250 (0.00%) 
Vascular disorders         
Venous stenosis  1  0/129 (0.00%)  3/254 (1.18%)  0/107 (0.00%)  1/250 (0.40%) 
Phlebitis  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Varicose vein  1  0/129 (0.00%)  1/254 (0.39%)  0/107 (0.00%)  0/250 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA-18.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo/Teriflunomide 7 mg Teriflunomide 7 mg/7 mg Placebo/Teriflunomide 14 mg Teriflunomide 14 mg/14 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   107/129 (82.95%)   195/254 (76.77%)   95/107 (88.79%)   197/250 (78.80%) 
Blood and lymphatic system disorders         
Anaemia  1  1/129 (0.78%)  7/254 (2.76%)  9/107 (8.41%)  12/250 (4.80%) 
Neutropenia  1  2/129 (1.55%)  6/254 (2.36%)  6/107 (5.61%)  6/250 (2.40%) 
Gastrointestinal disorders         
Diarrhoea  1  16/129 (12.40%)  24/254 (9.45%)  19/107 (17.76%)  30/250 (12.00%) 
Nausea  1  10/129 (7.75%)  20/254 (7.87%)  10/107 (9.35%)  29/250 (11.60%) 
Constipation  1  4/129 (3.10%)  10/254 (3.94%)  7/107 (6.54%)  15/250 (6.00%) 
Abdominal pain upper  1  3/129 (2.33%)  16/254 (6.30%)  4/107 (3.74%)  10/250 (4.00%) 
Abdominal pain  1  5/129 (3.88%)  22/254 (8.66%)  8/107 (7.48%)  9/250 (3.60%) 
Toothache  1  2/129 (1.55%)  13/254 (5.12%)  3/107 (2.80%)  9/250 (3.60%) 
Vomiting  1  8/129 (6.20%)  8/254 (3.15%)  5/107 (4.67%)  8/250 (3.20%) 
General disorders         
Fatigue  1  17/129 (13.18%)  37/254 (14.57%)  17/107 (15.89%)  26/250 (10.40%) 
Influenza like illness  1  1/129 (0.78%)  6/254 (2.36%)  1/107 (0.93%)  13/250 (5.20%) 
Infections and infestations         
Nasopharyngitis  1  34/129 (26.36%)  71/254 (27.95%)  29/107 (27.10%)  81/250 (32.40%) 
Influenza  1  19/129 (14.73%)  39/254 (15.35%)  20/107 (18.69%)  37/250 (14.80%) 
Urinary tract infection  1  20/129 (15.50%)  31/254 (12.20%)  19/107 (17.76%)  36/250 (14.40%) 
Sinusitis  1  7/129 (5.43%)  16/254 (6.30%)  5/107 (4.67%)  28/250 (11.20%) 
Upper respiratory tract infection  1  15/129 (11.63%)  29/254 (11.42%)  15/107 (14.02%)  28/250 (11.20%) 
Bronchitis  1  10/129 (7.75%)  17/254 (6.69%)  9/107 (8.41%)  26/250 (10.40%) 
Gastroenteritis  1  8/129 (6.20%)  10/254 (3.94%)  8/107 (7.48%)  14/250 (5.60%) 
Cystitis  1  9/129 (6.98%)  8/254 (3.15%)  4/107 (3.74%)  9/250 (3.60%) 
Respiratory tract infection  1  8/129 (6.20%)  10/254 (3.94%)  9/107 (8.41%)  7/250 (2.80%) 
Oral herpes  1  3/129 (2.33%)  17/254 (6.69%)  6/107 (5.61%)  6/250 (2.40%) 
Injury, poisoning and procedural complications         
Fall  1  9/129 (6.98%)  20/254 (7.87%)  8/107 (7.48%)  34/250 (13.60%) 
Contusion  1  4/129 (3.10%)  5/254 (1.97%)  8/107 (7.48%)  8/250 (3.20%) 
Investigations         
Alanine aminotransferase increased  1  18/129 (13.95%)  36/254 (14.17%)  18/107 (16.82%)  32/250 (12.80%) 
Gamma-glutamyltransferase increased  1  4/129 (3.10%)  16/254 (6.30%)  2/107 (1.87%)  12/250 (4.80%) 
Aspartate aminotransferase increased  1  4/129 (3.10%)  18/254 (7.09%)  4/107 (3.74%)  11/250 (4.40%) 
Blood pressure increased  1  8/129 (6.20%)  10/254 (3.94%)  5/107 (4.67%)  7/250 (2.80%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  10/129 (7.75%)  37/254 (14.57%)  16/107 (14.95%)  40/250 (16.00%) 
Pain in extremity  1  14/129 (10.85%)  27/254 (10.63%)  20/107 (18.69%)  32/250 (12.80%) 
Arthralgia  1  17/129 (13.18%)  31/254 (12.20%)  9/107 (8.41%)  28/250 (11.20%) 
Musculoskeletal pain  1  1/129 (0.78%)  11/254 (4.33%)  1/107 (0.93%)  16/250 (6.40%) 
Muscle spasms  1  6/129 (4.65%)  12/254 (4.72%)  4/107 (3.74%)  13/250 (5.20%) 
Nervous system disorders         
Headache  1  21/129 (16.28%)  42/254 (16.54%)  18/107 (16.82%)  42/250 (16.80%) 
Paraesthesia  1  6/129 (4.65%)  26/254 (10.24%)  13/107 (12.15%)  23/250 (9.20%) 
Dizziness  1  5/129 (3.88%)  14/254 (5.51%)  7/107 (6.54%)  14/250 (5.60%) 
Hypoaesthesia  1  4/129 (3.10%)  20/254 (7.87%)  10/107 (9.35%)  13/250 (5.20%) 
Psychiatric disorders         
Insomnia  1  6/129 (4.65%)  15/254 (5.91%)  8/107 (7.48%)  17/250 (6.80%) 
Depression  1  10/129 (7.75%)  24/254 (9.45%)  11/107 (10.28%)  15/250 (6.00%) 
Anxiety  1  3/129 (2.33%)  6/254 (2.36%)  6/107 (5.61%)  8/250 (3.20%) 
Renal and urinary disorders         
Micturition urgency  1  8/129 (6.20%)  4/254 (1.57%)  3/107 (2.80%)  9/250 (3.60%) 
Respiratory, thoracic and mediastinal disorders         
Cough  1  14/129 (10.85%)  22/254 (8.66%)  7/107 (6.54%)  19/250 (7.60%) 
Skin and subcutaneous tissue disorders         
Eczema  1  2/129 (1.55%)  7/254 (2.76%)  1/107 (0.93%)  15/250 (6.00%) 
Rash  1  6/129 (4.65%)  11/254 (4.33%)  6/107 (5.61%)  14/250 (5.60%) 
Alopecia  1  11/129 (8.53%)  12/254 (4.72%)  18/107 (16.82%)  6/250 (2.40%) 
Vascular disorders         
Hypertension  1  10/129 (7.75%)  22/254 (8.66%)  11/107 (10.28%)  37/250 (14.80%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA-18.1
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.
If no publication has occurred within 12 months of the completion of the study, the Investigator shall have the right to publish/present independently the results of the study. The Investigator shall provide the Sponsor with a copy of any such presentation/publication for comment at least 30 days before any presentation/submission for publication. If requested by the Sponsor, any presentation/submission shall be delayed up to 90 days, to allow the Sponsor to preserve its proprietary rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Trial Transparency Team
Organization: Sanofi
EMail: Contact-US@sanofi.com
Layout table for additonal information
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00803049    
Other Study ID Numbers: LTS6050
2006-003361-14 ( EudraCT Number )
First Submitted: December 1, 2008
First Posted: December 5, 2008
Results First Submitted: December 5, 2016
Results First Posted: January 30, 2017
Last Update Posted: January 30, 2017