ClinicalTrials.gov
ClinicalTrials.gov Menu

Long Term Safety of Teriflunomide When Added to Interferon-Beta or Glatiramer Acetate in Patients With 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: NCT00811395
Recruitment Status : Completed
First Posted : December 19, 2008
Results First Posted : December 31, 2012
Last Update Posted : December 31, 2012
Sponsor:
Information provided by (Responsible Party):
Sanofi

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Multiple Sclerosis
Interventions Drug: Teriflunomide
Drug: Placebo (for teriflunomide)
Drug: Interferon-β [IFN-β]
Drug: Glatiramer Acetate [GA]
Enrollment 182
Recruitment Details

107 and 110 participants who successfully completed 24-week visit in, respectively, PDY6045 and PDY6046 studies, were offered to continue their treatment in this extension study.

After signature of the informed consent and confirmation of selection criteria, 86 and 96 participants entered the extension study.

Pre-assignment Details

An Interactive Voice Response System was used to allocate kits containing the same treatment as in the initial study.

Analysis included all participants randomized in the initial studies and all data collected from randomization according to intent-to-treat principal.

Arm/Group Title Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA
Hide Arm/Group Description Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β] Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β] Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β] Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate [GA] Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate [GA] Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate [GA]
Period Title: Initial Treatment (PDY6045 or PDY6046)
Started 41 37 [1] 38 40 42 41
Completed 38 [2] 33 [2] 36 [2] 38 [3] 37 [3] 35 [3]
Not Completed 3 4 2 2 5 6
[1]
One participant received 7 mg instead of 14 mg as per randomization
[2]
completed 24-week treatment (for more information see PDY6045/NCT00489489 record)
[3]
completed 24-week treatment (for more information see PDY6046/NCT00475865 record)
Period Title: Extension Treatment
Started 31 [1] 28 [1] 27 [1] 37 [1] 30 [1] 29 [1]
Completed 29 [2] 22 [2] 24 [2] 34 [2] 30 [2] 27 [2]
Not Completed 2 6 3 3 0 2
Reason Not Completed
Adverse Event             1             2             2             2             0             1
Progressive disease             1             1             0             0             0             0
Participant did not wish to continue             0             3             0             1             0             1
Other than above             0             0             1             0             0             0
[1]
continued initial treatment
[2]
completed 48-week treatment
Arm/Group Title Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA Total
Hide Arm/Group Description Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β] Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β] Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β] Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate [GA] Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate [GA] Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate [GA] Total of all reporting groups
Overall Number of Baseline Participants 41 37 38 40 42 41 239
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 41 participants 37 participants 38 participants 40 participants 42 participants 41 participants 239 participants
<38 years 17 9 15 11 12 13 77
>=38 years 24 28 23 29 30 28 162
[1]
Measure Description: Baseline characteristics before randomization in the initial study (PDY6045 or PDY6046)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 37 participants 38 participants 40 participants 42 participants 41 participants 239 participants
Female
31
  75.6%
25
  67.6%
25
  65.8%
31
  77.5%
33
  78.6%
33
  80.5%
178
  74.5%
Male
10
  24.4%
12
  32.4%
13
  34.2%
9
  22.5%
9
  21.4%
8
  19.5%
61
  25.5%
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 41 participants 37 participants 38 participants 40 participants 42 participants 41 participants 239 participants
Europe 28 25 24 22 22 22 143
North America 13 12 14 18 20 19 96
[1]
Measure Description:

Europe: Austria, Germany, Italy, Spain and United Kingdom

North America: Canada and United States

1.Primary Outcome
Title Overview of Adverse Events [AE]
Hide Description AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.
Time Frame from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
Arm/Group Title Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β]
Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate [GA]
Overall Number of Participants Analyzed 41 37 38 40 42 41
Measure Type: Number
Unit of Measure: participants
Any AE 35 35 33 39 40 38
- serious AE 2 4 1 6 5 2
- AE leading to death 0 0 0 0 0 0
- AE leading to study drug discontinuation 2 3 3 2 3 5
2.Primary Outcome
Title Overview of AE With Potential Risk of Occurence
Hide Description

AE with potential risk of occurrence were defined as follows:

  • Hepatic disorders;
  • Immune effects, mainly effects on bone marrow and infection;
  • Pancreatic disorders;
  • Malignancy;
  • Skin disorders, mainly hair loss and hair thinning;
  • Pulmonary disorders;
  • Hypertension;
  • Peripheral neuropathy;
  • Psychiatric disorders;
  • Hypersensitivity.
Time Frame from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
Arm/Group Title Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β]
Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate [GA]
Overall Number of Participants Analyzed 41 37 38 40 42 41
Measure Type: Number
Unit of Measure: participants
Any AE with potential risk of occurence 28 30 30 34 33 32
- Hepatic disorder AE 7 11 13 5 4 5
- Immune effects related AE 16 21 20 27 22 21
- Pancreatic disorder AE 8 5 11 6 6 11
- Malignancy AE 0 0 0 0 0 0
- Hair loss / hair thinning AE 1 3 4 1 5 7
- Pulmonary disorder AE 0 0 0 0 1 0
- Hypertension-related AE 1 4 6 0 2 2
- Peripheral neuropathy AE 5 3 4 4 5 10
- Psychiatric disorder AE 1 1 2 3 3 1
- Hypersensitivity AE 6 4 4 4 6 10
3.Primary Outcome
Title Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA]
Hide Description

PCSA values are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review.

Hepatic parameters thresholds were defined as follows:

  • Alanine Aminotransferase [ALT] >3, 5, 10 or 20 Upper Normal Limit [ULN];
  • Aspartate aminotransferase [AST] >3, 5, 10 or 20 ULN;
  • Alkaline Phosphatase >1.5 ULN;
  • Total Bilirubin [TB] >1.5 or 2 ULN;
  • ALT >3 ULN and TB >2 ULN;
Time Frame from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured last (64 weeks max)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
Arm/Group Title Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β]
Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate [GA]
Overall Number of Participants Analyzed 41 37 38 40 42 41
Measure Type: Number
Unit of Measure: participants
ALT >3 ULN 2 1 3 1 0 1
- ALT >5 ULN 1 0 1 1 0 1
- ALT >10 ULN 0 0 0 1 0 0
AST >3 ULN 1 0 1 1 0 0
- AST >5 ULN 1 0 0 0 0 0
Alkaline Phosphatase >1.5 ULN 1 0 0 0 0 0
TB >1.5 ULN 0 0 0 0 0 0
ALT >3 ULN and TB >2 ULN 0 0 0 0 0 0
4.Secondary Outcome
Title Annualized Relapse Rate [ARR]: Poisson Regression Estimates
Hide Description

ARR is obtained from the total number of confirmed relapses that occured during the treatment period divided by the sum of the treatment durations.

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 Expanded Disability Status Scale [EDSS] score or Functional System scores.

To account for the different treatment durations among participants, two Poisson regression models with robust error variance were used (total number of confirmed relapses as response variable, log-transformed treatment duration as "offset" variable and:

  • Model 1 (IFN-β groups): treatment group, region of enrollment and IFN-β dose level as covariates
  • Model 2 (GA groups): treatment group and region of enrollment as covariates)
Time Frame 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
Arm/Group Title Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β]
Placebo (for Teriflunomide) once daily concomitantly with glatiramer acetate [GA]
Teriflunomide 7 mg once daily concomitantly with glatiramer acetate [GA]
Teriflunomide 14 mg once daily concomitantly with glatiramer acetate [GA]
Overall Number of Participants Analyzed 41 37 38 41 42 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: relapses per year
0.343
(0.162 to 0.727)
0.231
(0.101 to 0.529)
0.144
(0.065 to 0.318)
0.420
(0.270 to 0.654)
0.262
(0.140 to 0.489)
0.497
(0.316 to 0.783)
5.Secondary Outcome
Title Overview of 12-week Sustained Disability Progression
Hide Description

12-week sustained disability progression was defined as an increase from baseline of at least 1-point in EDSS score (at least 0.5-point for participants with baseline EDSS score >5.5) that persisted for at least 12 weeks.

If no disability progression was observed on or before last EDSS evaluation before study drug discontinuation, then the participant was considered as free of disability progression.

Time Frame 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
Arm/Group Title Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β]
Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate [GA]
Overall Number of Participants Analyzed 41 37 38 41 42 40
Measure Type: Number
Unit of Measure: participants
Disability progression 0 3 2 4 1 4
Free of disability progression 40 33 36 37 41 36
6.Secondary Outcome
Title Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints
Hide Description

Probability of disability progression at 24 and 48 weeks was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first EDSS increase. Participants free of disability progression were censored at the date of the last on-treatment EDSS evaluation.

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. Probability of event at time t is 1 minus the probability of being event-free for the amount of time t.

Time Frame 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
Arm/Group Title Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β]
Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate [GA]
Overall Number of Participants Analyzed 41 37 38 41 42 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percent probability
Probability of disability progression at 24 weeks
0.0
(0.0 to 0.0)
3.0
(0.0 to 8.9)
2.7
(0.0 to 7.9)
2.5
(0.0 to 7.3)
0.0
(0.0 to 0.0)
5.6
(0.0 to 13.2)
Probability of disability progression at 48 weeks
0.0
(0.0 to 0.0)
11.1
(0.0 to 23.1)
6.4
(0.0 to 15.2)
10.6
(0.7 to 20.4)
3.3
(0.0 to 9.8)
12.8
(1.0 to 24.6)
7.Secondary Outcome
Title Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)
Hide Description

Total lesion volume is the sum of the total volume of all T2-lesions and the total volume all T1-hypointense post-gadolinium lesions measured through T2/proton density scan analysis and gadolinium-enhanced T1 scan analysis.

Least-square means were estimated using two Mixed-effect models with repeated measures [MMRM] on cubic root transformed volume data:

  • Model 1 (IFN-β groups): treatment group, region of enrollment, IFN-β dose level, visit, treatment-by-visit interaction, baseline value (cubic root transformed), and baseline-by-visit interaction as factors;
  • Model 2 (GA groups): treatment group, region of enrollment, visit, treatment-by-visit interaction, baseline value (cubic root transformed), and baseline-by-visit interaction as factors.
Time Frame baseline (before randomization in PDY6045 or PDY6046) and 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
Arm/Group Title Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β]
Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate [GA]
Overall Number of Participants Analyzed 41 37 38 41 42 40
Least Squares Mean (Standard Error)
Unit of Measure: mililiters (mL)
-0.017  (0.028) -0.011  (0.030) -0.012  (0.029) 0.016  (0.036) -0.010  (0.037) -0.063  (0.039)
8.Secondary Outcome
Title Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)
Hide Description

Number of Gd-enhancing T1-lesions per scan is obtained from the total number of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study.

To account for the different number of scans among participants, two Poisson regression models with robust error variance were used (total number of Gd-enhancing T1-lesions as response variable, log-transformed number of scans as "offset" variable and:

  • Model 1 (IFN-β groups): Treatment group, region of enrollment, IFN-β dose level and baseline number of Gd-enhancing T1-lesions as covariates
  • Model 2 (GA groups): Treatment group, region of enrollment and baseline number of Gd-enhancing T1-lesions as covariates)
Time Frame 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
Arm/Group Title Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β]
Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate [GA]
Overall Number of Participants Analyzed 41 37 38 41 42 40
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: lesions per scan
0.521
(0.318 to 0.854)
0.080
(0.032 to 0.204)
0.090
(0.052 to 0.154)
0.333
(0.171 to 0.649)
0.120
(0.059 to 0.243)
0.178
(0.098 to 0.324)
9.Secondary Outcome
Title Cerebral MRI Assessment: Total Volume of Gd-enhancing T1-lesions Per Scan
Hide Description Total volume of Gd-enhancing T1-lesions per scan is obtained from the sum of the volumes of Gd-enhancing T1-lesions observed during the study divided by the total number of scans performed during the study.
Time Frame 48 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
Arm/Group Title Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA
Hide Arm/Group Description:
Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β]
Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate [GA]
Overall Number of Participants Analyzed 41 37 38 41 42 40
Measure Type: Number
Unit of Measure: mililiters per scan
0.068 0.019 0.020 0.052 0.031 0.014
Time Frame All Adverse Events (AE) were collected regardless of seriousness or relationship to the drug, spanning from signature of the Informed Consent up to the last visit.
Adverse Event Reporting Description The analysis was performed on the exposed population and included all AE that developed or worsened from first study drug intake in PDY6045/PDY6046 study up to 112 days after last intake in initial study or in the extension study, whichever occured first (64 weeks max).
 
Arm/Group Title Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA
Hide Arm/Group Description Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β] Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β] Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β] Placebo (for Teriflunomide) once daily concomitantly with glatiramer acetate [GA] Teriflunomide 7 mg once daily concomitantly with glatiramer acetate [GA] Teriflunomide 14 mg once daily concomitantly with glatiramer acetate [GA]
All-Cause Mortality
Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/41 (4.88%)   4/37 (10.81%)   1/38 (2.63%)   6/40 (15.00%)   5/42 (11.90%)   2/41 (4.88%) 
Ear and labyrinth disorders             
Vertigo * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  1/40 (2.50%)  0/42 (0.00%)  0/41 (0.00%) 
Hepatobiliary disorders             
Cholecystitis * 1  0/41 (0.00%)  0/37 (0.00%)  1/38 (2.63%)  0/40 (0.00%)  0/42 (0.00%)  0/41 (0.00%) 
Infections and infestations             
Abscess * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  1/40 (2.50%)  0/42 (0.00%)  0/41 (0.00%) 
Cystitis * 1  0/41 (0.00%)  0/37 (0.00%)  1/38 (2.63%)  0/40 (0.00%)  0/42 (0.00%)  0/41 (0.00%) 
Herpes zoster * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  1/40 (2.50%)  0/42 (0.00%)  0/41 (0.00%) 
Lobar pneumonia * 1  0/41 (0.00%)  0/37 (0.00%)  1/38 (2.63%)  0/40 (0.00%)  0/42 (0.00%)  0/41 (0.00%) 
Mastoiditis * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  0/40 (0.00%)  1/42 (2.38%)  0/41 (0.00%) 
Otitis media * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  0/40 (0.00%)  1/42 (2.38%)  0/41 (0.00%) 
Injury, poisoning and procedural complications             
Ankle fracture * 1  1/41 (2.44%)  0/37 (0.00%)  0/38 (0.00%)  0/40 (0.00%)  0/42 (0.00%)  0/41 (0.00%) 
Facial bones fracture * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  1/40 (2.50%)  0/42 (0.00%)  0/41 (0.00%) 
Fall * 1  0/41 (0.00%)  1/37 (2.70%)  0/38 (0.00%)  0/40 (0.00%)  0/42 (0.00%)  0/41 (0.00%) 
Tendon rupture * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  0/40 (0.00%)  0/42 (0.00%)  1/41 (2.44%) 
Investigations             
Alanine aminotransferase increased * 1  1/41 (2.44%)  1/37 (2.70%)  0/38 (0.00%)  0/40 (0.00%)  2/42 (4.76%)  0/41 (0.00%) 
Hepatic enzyme increased * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  1/40 (2.50%)  0/42 (0.00%)  0/41 (0.00%) 
Musculoskeletal and connective tissue disorders             
Musculoskeletal stiffness * 1  0/41 (0.00%)  1/37 (2.70%)  0/38 (0.00%)  0/40 (0.00%)  0/42 (0.00%)  0/41 (0.00%) 
Pseudarthrosis * 1  0/41 (0.00%)  1/37 (2.70%)  0/38 (0.00%)  0/40 (0.00%)  0/42 (0.00%)  0/41 (0.00%) 
Nervous system disorders             
Cerebral ischaemia * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  1/40 (2.50%)  0/42 (0.00%)  0/41 (0.00%) 
Epilepsy * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  0/40 (0.00%)  1/42 (2.38%)  0/41 (0.00%) 
Muscle spasticity * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  1/40 (2.50%)  0/42 (0.00%)  0/41 (0.00%) 
Psychiatric disorders             
Suicidal ideation * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  0/40 (0.00%)  1/42 (2.38%)  1/41 (2.44%) 
Suicide attempt * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  0/40 (0.00%)  1/42 (2.38%)  0/41 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Interstitial lung disease * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  0/40 (0.00%)  1/42 (2.38%)  0/41 (0.00%) 
Vascular disorders             
Deep vein thrombosis * 1  0/41 (0.00%)  1/37 (2.70%)  0/38 (0.00%)  0/40 (0.00%)  0/42 (0.00%)  0/41 (0.00%) 
Hypertension * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  0/40 (0.00%)  1/42 (2.38%)  0/41 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo + IFN-β Teriflunomide 7 mg + IFN-β Teriflunomide 14 mg + IFN-β Placebo + GA Teriflunomide 7 mg + GA Teriflunomide 14 mg + GA
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   28/41 (68.29%)   33/37 (89.19%)   32/38 (84.21%)   34/40 (85.00%)   30/42 (71.43%)   34/41 (82.93%) 
Ear and labyrinth disorders             
Vertigo * 1  2/41 (4.88%)  0/37 (0.00%)  0/38 (0.00%)  3/40 (7.50%)  1/42 (2.38%)  0/41 (0.00%) 
Gastrointestinal disorders             
Abdominal discomfort * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  0/40 (0.00%)  3/42 (7.14%)  2/41 (4.88%) 
Abdominal pain upper * 1  3/41 (7.32%)  1/37 (2.70%)  3/38 (7.89%)  2/40 (5.00%)  1/42 (2.38%)  1/41 (2.44%) 
Constipation * 1  0/41 (0.00%)  1/37 (2.70%)  0/38 (0.00%)  0/40 (0.00%)  2/42 (4.76%)  4/41 (9.76%) 
Diarrhoea * 1  6/41 (14.63%)  4/37 (10.81%)  4/38 (10.53%)  2/40 (5.00%)  3/42 (7.14%)  8/41 (19.51%) 
Nausea * 1  3/41 (7.32%)  0/37 (0.00%)  5/38 (13.16%)  3/40 (7.50%)  5/42 (11.90%)  5/41 (12.20%) 
Vomiting * 1  2/41 (4.88%)  1/37 (2.70%)  4/38 (10.53%)  0/40 (0.00%)  0/42 (0.00%)  1/41 (2.44%) 
General disorders             
Asthenia * 1  1/41 (2.44%)  1/37 (2.70%)  3/38 (7.89%)  0/40 (0.00%)  0/42 (0.00%)  1/41 (2.44%) 
Fatigue * 1  4/41 (9.76%)  2/37 (5.41%)  5/38 (13.16%)  7/40 (17.50%)  4/42 (9.52%)  7/41 (17.07%) 
Oedema peripheral * 1  1/41 (2.44%)  0/37 (0.00%)  0/38 (0.00%)  3/40 (7.50%)  2/42 (4.76%)  2/41 (4.88%) 
Infections and infestations             
Bronchitis * 1  0/41 (0.00%)  1/37 (2.70%)  2/38 (5.26%)  1/40 (2.50%)  3/42 (7.14%)  2/41 (4.88%) 
Ear infection * 1  0/41 (0.00%)  0/37 (0.00%)  2/38 (5.26%)  0/40 (0.00%)  0/42 (0.00%)  0/41 (0.00%) 
Gastroenteritis * 1  0/41 (0.00%)  1/37 (2.70%)  0/38 (0.00%)  3/40 (7.50%)  0/42 (0.00%)  0/41 (0.00%) 
Influenza * 1  3/41 (7.32%)  1/37 (2.70%)  0/38 (0.00%)  1/40 (2.50%)  1/42 (2.38%)  2/41 (4.88%) 
Nasopharyngitis * 1  3/41 (7.32%)  3/37 (8.11%)  5/38 (13.16%)  6/40 (15.00%)  7/42 (16.67%)  4/41 (9.76%) 
Respiratory tract infection * 1  2/41 (4.88%)  2/37 (5.41%)  0/38 (0.00%)  0/40 (0.00%)  1/42 (2.38%)  0/41 (0.00%) 
Respiratory tract infection viral * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  5/40 (12.50%)  2/42 (4.76%)  1/41 (2.44%) 
Sinusitis * 1  0/41 (0.00%)  1/37 (2.70%)  2/38 (5.26%)  0/40 (0.00%)  1/42 (2.38%)  4/41 (9.76%) 
Upper respiratory tract infection * 1  4/41 (9.76%)  2/37 (5.41%)  2/38 (5.26%)  6/40 (15.00%)  2/42 (4.76%)  4/41 (9.76%) 
Urinary tract infection * 1  7/41 (17.07%)  4/37 (10.81%)  1/38 (2.63%)  6/40 (15.00%)  5/42 (11.90%)  4/41 (9.76%) 
Injury, poisoning and procedural complications             
Contusion * 1  0/41 (0.00%)  1/37 (2.70%)  2/38 (5.26%)  1/40 (2.50%)  1/42 (2.38%)  2/41 (4.88%) 
Procedural pain * 1  0/41 (0.00%)  0/37 (0.00%)  2/38 (5.26%)  0/40 (0.00%)  1/42 (2.38%)  0/41 (0.00%) 
Investigations             
Alanine aminotransferase increased * 1  6/41 (14.63%)  7/37 (18.92%)  12/38 (31.58%)  2/40 (5.00%)  3/42 (7.14%)  2/41 (4.88%) 
Aspartate aminotransferase increased * 1  1/41 (2.44%)  7/37 (18.92%)  4/38 (10.53%)  0/40 (0.00%)  1/42 (2.38%)  0/41 (0.00%) 
Blood creatine phosphokinase increased * 1  0/41 (0.00%)  3/37 (8.11%)  1/38 (2.63%)  1/40 (2.50%)  1/42 (2.38%)  0/41 (0.00%) 
Blood pressure increased * 1  0/41 (0.00%)  1/37 (2.70%)  3/38 (7.89%)  0/40 (0.00%)  0/42 (0.00%)  1/41 (2.44%) 
Blood triglycerides increased * 1  1/41 (2.44%)  1/37 (2.70%)  2/38 (5.26%)  1/40 (2.50%)  1/42 (2.38%)  0/41 (0.00%) 
Lipase increased * 1  0/41 (0.00%)  0/37 (0.00%)  2/38 (5.26%)  1/40 (2.50%)  0/42 (0.00%)  3/41 (7.32%) 
Lymphocyte count decreased * 1  1/41 (2.44%)  4/37 (10.81%)  5/38 (13.16%)  0/40 (0.00%)  0/42 (0.00%)  0/41 (0.00%) 
Neutrophil count decreased * 1  1/41 (2.44%)  1/37 (2.70%)  4/38 (10.53%)  0/40 (0.00%)  1/42 (2.38%)  1/41 (2.44%) 
Protein urine present * 1  3/41 (7.32%)  0/37 (0.00%)  0/38 (0.00%)  0/40 (0.00%)  0/42 (0.00%)  0/41 (0.00%) 
White blood cell count decreased * 1  3/41 (7.32%)  3/37 (8.11%)  4/38 (10.53%)  0/40 (0.00%)  0/42 (0.00%)  1/41 (2.44%) 
Musculoskeletal and connective tissue disorders             
Arthralgia * 1  2/41 (4.88%)  1/37 (2.70%)  2/38 (5.26%)  2/40 (5.00%)  1/42 (2.38%)  1/41 (2.44%) 
Back pain * 1  1/41 (2.44%)  2/37 (5.41%)  4/38 (10.53%)  2/40 (5.00%)  3/42 (7.14%)  1/41 (2.44%) 
Pain in extremity * 1  1/41 (2.44%)  1/37 (2.70%)  1/38 (2.63%)  4/40 (10.00%)  3/42 (7.14%)  2/41 (4.88%) 
Nervous system disorders             
Carpal tunnel syndrome * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  0/40 (0.00%)  0/42 (0.00%)  3/41 (7.32%) 
Dizziness * 1  2/41 (4.88%)  0/37 (0.00%)  1/38 (2.63%)  3/40 (7.50%)  1/42 (2.38%)  1/41 (2.44%) 
Headache * 1  2/41 (4.88%)  2/37 (5.41%)  6/38 (15.79%)  7/40 (17.50%)  6/42 (14.29%)  7/41 (17.07%) 
Hypoaesthesia * 1  2/41 (4.88%)  0/37 (0.00%)  2/38 (5.26%)  2/40 (5.00%)  2/42 (4.76%)  2/41 (4.88%) 
Muscle spasticity * 1  0/41 (0.00%)  0/37 (0.00%)  0/38 (0.00%)  0/40 (0.00%)  4/42 (9.52%)  0/41 (0.00%) 
Paraesthesia * 1  0/41 (0.00%)  1/37 (2.70%)  0/38 (0.00%)  0/40 (0.00%)  0/42 (0.00%)  3/41 (7.32%) 
Sciatica * 1  0/41 (0.00%)  2/37 (5.41%)  1/38 (2.63%)  2/40 (5.00%)  1/42 (2.38%)  1/41 (2.44%) 
Psychiatric disorders             
Anxiety * 1  1/41 (2.44%)  2/37 (5.41%)  1/38 (2.63%)  1/40 (2.50%)  0/42 (0.00%)  0/41 (0.00%) 
Depression * 1  1/41 (2.44%)  1/37 (2.70%)  1/38 (2.63%)  2/40 (5.00%)  5/42 (11.90%)  0/41 (0.00%) 
Insomnia * 1  1/41 (2.44%)  0/37 (0.00%)  3/38 (7.89%)  1/40 (2.50%)  1/42 (2.38%)  3/41 (7.32%) 
Renal and urinary disorders             
Micturition urgency * 1  0/41 (0.00%)  1/37 (2.70%)  0/38 (0.00%)  1/40 (2.50%)  3/42 (7.14%)  3/41 (7.32%) 
Respiratory, thoracic and mediastinal disorders             
Cough * 1  3/41 (7.32%)  0/37 (0.00%)  2/38 (5.26%)  1/40 (2.50%)  0/42 (0.00%)  1/41 (2.44%) 
Oropharyngeal pain * 1  1/41 (2.44%)  2/37 (5.41%)  2/38 (5.26%)  1/40 (2.50%)  0/42 (0.00%)  0/41 (0.00%) 
Skin and subcutaneous tissue disorders             
Alopecia * 1  1/41 (2.44%)  3/37 (8.11%)  3/38 (7.89%)  1/40 (2.50%)  5/42 (11.90%)  7/41 (17.07%) 
Dry skin * 1  1/41 (2.44%)  0/37 (0.00%)  2/38 (5.26%)  0/40 (0.00%)  1/42 (2.38%)  0/41 (0.00%) 
Pruritus * 1  0/41 (0.00%)  2/37 (5.41%)  0/38 (0.00%)  1/40 (2.50%)  1/42 (2.38%)  1/41 (2.44%) 
Rash * 1  1/41 (2.44%)  0/37 (0.00%)  1/38 (2.63%)  1/40 (2.50%)  3/42 (7.14%)  6/41 (14.63%) 
Urticaria * 1  0/41 (0.00%)  2/37 (5.41%)  1/38 (2.63%)  0/40 (0.00%)  1/42 (2.38%)  0/41 (0.00%) 
Vascular disorders             
Hypertension * 1  1/41 (2.44%)  3/37 (8.11%)  4/38 (10.53%)  0/40 (0.00%)  1/42 (2.38%)  1/41 (2.44%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.1
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 after trial completion, the Investigator can publish the results. Prior to publication, the sponsor shall review the manuscript and can request changes, provided they do not jeopardize the accuracy and/or the scientific value of the publication. The approval is given in writing by the sponsor, not exceeding 90 days.

To protect by property right the sponsor can postpone the publication of any information, for a period not exceeding 18 months.

Results Point of Contact
Name/Title: Trial Transparency Team
Organization: sanofi-aventis
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00811395     History of Changes
Other Study ID Numbers: LTS6047
HMR1726D/2005 ( Other Identifier: HMR )
2007-003997-24 ( EudraCT Number )
First Submitted: December 18, 2008
First Posted: December 19, 2008
Results First Submitted: October 3, 2012
Results First Posted: December 31, 2012
Last Update Posted: December 31, 2012