Multiple Sclerosis
Conditions
Keywords
MS, glatiramer acetate, adjunctive therapy, relapses
Brief summary
The primary objective was to estimate the tolerability and safety of 2 doses of Teriflunomide administered once daily for 24 weeks, compared to placebo, in patients with multiple sclerosis \[MS\] with relapses who were on a stable dose of Glatiramer Acetate \[GA\]. The secondary objectives were: * to estimate the effect of the 2 doses of Teriflunomide, compared to placebo, in combination with a stable dose of GA on Magnetic Resonance Imaging \[MRI\] parameters, relapse rate and patient-reported fatigue; * to perform pharmacokinetic analyses of the 2 doses of teriflunomide in combination with a stable dose of GA.
Detailed description
The duration of the study period for a participant was approximatively 44 weeks broken down as follows: * Screening period up to 4 weeks, * 24-week double-blind treatment period\*, * 16-week post-treatment elimination follow-up period. '\*' Participants successfully completing the week 24 visit were offered the opportunity to enter the optional long-term extension study LTS6047 - NCT00811395.
Interventions
DRUGTeriflunomide
Film-coated tablet Oral administration
Film-coated tablet Oral administration
Solution in prefilled syringe for subcutaneous injection
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Definite MS diagnosis according to McDonald's criteria; * Relapsing clinical course, with or without progression; * Expanded Disability Status Scale \[EDSS\] less or equal to 5.5 (ambulatory); * Stable dose of Glatiramer Acetate \[GA\] for at least 26 weeks prior to the screening visit; * No onset of MS relapse in the preceding 60 days prior to randomization; * Clinically stable for 4 weeks prior to randomization.
Exclusion criteria
* Other chronic disease of the immune system, liver function impairment or chronic pancreatic disease; * Pregnant or nursing woman; * Alcohol or drug abuse; * Use of cladribine, Mitoxantrone, or other immunosuppressant agents such as Azathioprine, Cyclophosphamide, Cyclosporin, Methotrexate or Mycophenolate before enrollment; * Human immunodeficiency virus \[HIV\] positive status; * Any known condition or circumstance that would prevent in the investigator's opinion compliance or completion of the study. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overview of Adverse Events (AE] | from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max) | AE are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study. |
| Overview of AE With Potential Risk of Occurrence | from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max) | 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. |
| Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | from first study drug intake up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Relapse Rate [ARR]: Poisson Regression Estimates | 24 weeks | 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, 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 and region of enrollment as covariates). |
| Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) | baseline (before randomization) and 24 weeks | 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 a Mixed-effect model with repeated measures \[MMRM\] on cubic root transformed volume data (treatment group, region of enrollment, visit, treatment-by-visit interaction, baseline value (cubic root transformed), and baseline-by-visit interaction as factors). |
| Pharmacokinetic [PK]: Teriflunomide Plasma Concentration | 24 weeks | Plasma concentrations of teriflunomide were measured using validated liquid chromatography-tandem mass spectrometry methods. |
| Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates) | 24 weeks | 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, a Poisson regression model with robust error variance was used (total number of Gd-enhancing T1-lesions as response variable; log-transformed number of scans as offset variable; treatment group, region of enrollment and baseline number of Gd-enhancing T1-lesions as covariates). |
| Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan | 24 weeks | 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. |
Countries
Austria, Canada, Germany, Italy, United Kingdom, United States
Participant flow
Recruitment details
The recruitment initiated in April 2007 was completed in December 2008. A total of 148 patients were screened at 24 sites in 6 countries.
Pre-assignment details
Randomization was stratified by country. Assignment to groups was done centrally using an Interactive Voice Response System (IVRS\] in a 1:1:1 ratio after confirmation of the selection criteria. 123 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Placebo + GA Placebo (for Teriflunomide) once daily concomitantly with glatiramer acetate \[GA\] for 24 weeks | 41 |
| Teriflunomide 7 mg + GA Teriflunomide 7 mg once daily concomitantly with glatiramer acetate \[GA\] for 24 weeks | 42 |
| Teriflunomide 14 mg + GA Teriflunomide 14 mg once daily concomitantly with glatiramer acetate \[GA\] for 24 weeks | 40 |
| Total | 123 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 | 4 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 |
| Overall Study | Other than above | 0 | 1 | 0 |
| Overall Study | Participant did not wish to continue | 1 | 0 | 0 |
| Overall Study | Progressive disease | 0 | 1 | 2 |
Baseline characteristics
| Characteristic | Placebo + GA | Teriflunomide 7 mg + GA | Teriflunomide 14 mg + GA | Total |
|---|---|---|---|---|
| Age Continuous | 41.8 years STANDARD_DEVIATION 8.5 | 42.1 years STANDARD_DEVIATION 7.8 | 40.3 years STANDARD_DEVIATION 7.5 | 41.4 years STANDARD_DEVIATION 7.9 |
| Baseline Expanded Disability Status Scale [EDSS] score | 2.54 units on a scale STANDARD_DEVIATION 1.11 | 2.43 units on a scale STANDARD_DEVIATION 1.23 | 2.60 units on a scale STANDARD_DEVIATION 1.28 | 2.52 units on a scale STANDARD_DEVIATION 1.2 |
| MS subtype Progressive Relapsing | 0 participants | 0 participants | 0 participants | 0 participants |
| MS subtype Relapsing Remitting | 39 participants | 40 participants | 37 participants | 116 participants |
| MS subtype Secondary Progressive | 2 participants | 2 participants | 3 participants | 7 participants |
| Number of MS relapses Within the past 2 years | 1 MS relapses | 1 MS relapses | 1 MS relapses | 1 MS relapses |
| Number of MS relapses Within the past year | 1 MS relapses | 1 MS relapses | 1 MS relapses | 1 MS relapses |
| Region of Enrollment Europe | 23 participants | 22 participants | 21 participants | 66 participants |
| Region of Enrollment North America | 18 participants | 20 participants | 19 participants | 57 participants |
| Sex: Female, Male Female | 32 Participants | 33 Participants | 32 Participants | 97 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 8 Participants | 26 Participants |
| Time since first diagnosis of Multiple Sclerosis [MS] | 7.61 years STANDARD_DEVIATION 6.04 | 8.82 years STANDARD_DEVIATION 5.85 | 7.60 years STANDARD_DEVIATION 6.03 | 8.02 years STANDARD_DEVIATION 5.95 |
| Time since most recent MS relapse onset | 24.90 months STANDARD_DEVIATION 34.84 | 21.52 months STANDARD_DEVIATION 30.48 | 23.88 months STANDARD_DEVIATION 31.53 | 23.41 months STANDARD_DEVIATION 32.09 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 20 / 41 | 20 / 42 | 25 / 40 |
| serious Total, serious adverse events | 3 / 41 | 3 / 42 | 1 / 40 |
Outcome results
Primary
Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA)
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 up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)
Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | ALT >3 ULN | 1 participants |
| Placebo + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | - ALT >5 ULN | 1 participants |
| Placebo + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | - ALT >10 ULN | 1 participants |
| Placebo + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | AST >3 ULN | 1 participants |
| Placebo + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | - AST >5 ULN | 1 participants |
| Placebo + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | Alkaline Phosphatase >1.5 ULN | 0 participants |
| Placebo + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | TB >1.5 ULN | 0 participants |
| Placebo + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | ALT >3 ULN and TB >2 ULN | 0 participants |
| Teriflunomide 7 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | - ALT >10 ULN | 0 participants |
| Teriflunomide 7 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | TB >1.5 ULN | 0 participants |
| Teriflunomide 7 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | AST >3 ULN | 0 participants |
| Teriflunomide 7 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | - AST >5 ULN | 0 participants |
| Teriflunomide 7 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | Alkaline Phosphatase >1.5 ULN | 0 participants |
| Teriflunomide 7 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | ALT >3 ULN | 0 participants |
| Teriflunomide 7 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | - ALT >5 ULN | 0 participants |
| Teriflunomide 7 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | ALT >3 ULN and TB >2 ULN | 0 participants |
| Teriflunomide 14 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | - ALT >10 ULN | 0 participants |
| Teriflunomide 14 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | - ALT >5 ULN | 1 participants |
| Teriflunomide 14 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | ALT >3 ULN | 1 participants |
| Teriflunomide 14 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | AST >3 ULN | 0 participants |
| Teriflunomide 14 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | TB >1.5 ULN | 0 participants |
| Teriflunomide 14 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | Alkaline Phosphatase >1.5 ULN | 0 participants |
| Teriflunomide 14 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | - AST >5 ULN | 0 participants |
| Teriflunomide 14 mg + GA | Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) | ALT >3 ULN and TB >2 ULN | 0 participants |
Primary
Overview of Adverse Events (AE]
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 up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)
Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + GA | Overview of Adverse Events (AE] | Any AE | 32 participants |
| Placebo + GA | Overview of Adverse Events (AE] | - AE leading to study drug discontinuation | 0 participants |
| Placebo + GA | Overview of Adverse Events (AE] | - serious AE | 3 participants |
| Placebo + GA | Overview of Adverse Events (AE] | - AE leading to death | 0 participants |
| Teriflunomide 7 mg + GA | Overview of Adverse Events (AE] | Any AE | 35 participants |
| Teriflunomide 7 mg + GA | Overview of Adverse Events (AE] | - AE leading to death | 0 participants |
| Teriflunomide 7 mg + GA | Overview of Adverse Events (AE] | - AE leading to study drug discontinuation | 3 participants |
| Teriflunomide 7 mg + GA | Overview of Adverse Events (AE] | - serious AE | 3 participants |
| Teriflunomide 14 mg + GA | Overview of Adverse Events (AE] | - AE leading to study drug discontinuation | 4 participants |
| Teriflunomide 14 mg + GA | Overview of Adverse Events (AE] | - serious AE | 1 participants |
| Teriflunomide 14 mg + GA | Overview of Adverse Events (AE] | - AE leading to death | 0 participants |
| Teriflunomide 14 mg + GA | Overview of Adverse Events (AE] | Any AE | 35 participants |
Primary
Overview of AE With Potential Risk of Occurrence
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 up to 112 days after last intake or up to the first intake in the extension study LTS6047, whichever occured first (40 weeks max)
Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + GA | Overview of AE With Potential Risk of Occurrence | Any AE with potential risk of occurence | 24 participants |
| Placebo + GA | Overview of AE With Potential Risk of Occurrence | - Hepatic disorder AE | 4 participants |
| Placebo + GA | Overview of AE With Potential Risk of Occurrence | - Pancreatic disorder AE | 6 participants |
| Placebo + GA | Overview of AE With Potential Risk of Occurrence | - Pulmonary disorder AE | 0 participants |
| Placebo + GA | Overview of AE With Potential Risk of Occurrence | - Immune effects related AE | 18 participants |
| Placebo + GA | Overview of AE With Potential Risk of Occurrence | - Hair loss / Hair thinning AE | 1 participants |
| Placebo + GA | Overview of AE With Potential Risk of Occurrence | - Hypertension-related AE | 0 participants |
| Placebo + GA | Overview of AE With Potential Risk of Occurrence | - Peripheral neuropathy AE | 2 participants |
| Placebo + GA | Overview of AE With Potential Risk of Occurrence | - Hypersensitivity AE | 3 participants |
| Placebo + GA | Overview of AE With Potential Risk of Occurrence | - Malignancy AE | 0 participants |
| Placebo + GA | Overview of AE With Potential Risk of Occurrence | - Psychiatric disorder AE | 1 participants |
| Teriflunomide 7 mg + GA | Overview of AE With Potential Risk of Occurrence | - Hypersensitivity AE | 3 participants |
| Teriflunomide 7 mg + GA | Overview of AE With Potential Risk of Occurrence | - Immune effects related AE | 18 participants |
| Teriflunomide 7 mg + GA | Overview of AE With Potential Risk of Occurrence | - Psychiatric disorder AE | 3 participants |
| Teriflunomide 7 mg + GA | Overview of AE With Potential Risk of Occurrence | - Hair loss / Hair thinning AE | 5 participants |
| Teriflunomide 7 mg + GA | Overview of AE With Potential Risk of Occurrence | - Malignancy AE | 0 participants |
| Teriflunomide 7 mg + GA | Overview of AE With Potential Risk of Occurrence | - Hypertension-related AE | 1 participants |
| Teriflunomide 7 mg + GA | Overview of AE With Potential Risk of Occurrence | - Peripheral neuropathy AE | 1 participants |
| Teriflunomide 7 mg + GA | Overview of AE With Potential Risk of Occurrence | Any AE with potential risk of occurence | 28 participants |
| Teriflunomide 7 mg + GA | Overview of AE With Potential Risk of Occurrence | - Hepatic disorder AE | 2 participants |
| Teriflunomide 7 mg + GA | Overview of AE With Potential Risk of Occurrence | - Pancreatic disorder AE | 5 participants |
| Teriflunomide 7 mg + GA | Overview of AE With Potential Risk of Occurrence | - Pulmonary disorder AE | 1 participants |
| Teriflunomide 14 mg + GA | Overview of AE With Potential Risk of Occurrence | - Psychiatric disorder AE | 1 participants |
| Teriflunomide 14 mg + GA | Overview of AE With Potential Risk of Occurrence | - Pulmonary disorder AE | 0 participants |
| Teriflunomide 14 mg + GA | Overview of AE With Potential Risk of Occurrence | - Hypersensitivity AE | 8 participants |
| Teriflunomide 14 mg + GA | Overview of AE With Potential Risk of Occurrence | - Hypertension-related AE | 0 participants |
| Teriflunomide 14 mg + GA | Overview of AE With Potential Risk of Occurrence | - Immune effects related AE | 15 participants |
| Teriflunomide 14 mg + GA | Overview of AE With Potential Risk of Occurrence | Any AE with potential risk of occurence | 28 participants |
| Teriflunomide 14 mg + GA | Overview of AE With Potential Risk of Occurrence | - Peripheral neuropathy AE | 5 participants |
| Teriflunomide 14 mg + GA | Overview of AE With Potential Risk of Occurrence | - Hair loss / Hair thinning AE | 7 participants |
| Teriflunomide 14 mg + GA | Overview of AE With Potential Risk of Occurrence | - Pancreatic disorder AE | 6 participants |
| Teriflunomide 14 mg + GA | Overview of AE With Potential Risk of Occurrence | - Hepatic disorder AE | 5 participants |
| Teriflunomide 14 mg + GA | Overview of AE With Potential Risk of Occurrence | - Malignancy AE | 0 participants |
Secondary
Annualized Relapse Rate [ARR]: Poisson Regression Estimates
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, 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 and region of enrollment as covariates).
Time frame: 24 weeks
Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + GA | Annualized Relapse Rate [ARR]: Poisson Regression Estimates | 0.475 relapses per year |
| Teriflunomide 7 mg + GA | Annualized Relapse Rate [ARR]: Poisson Regression Estimates | 0.311 relapses per year |
| Teriflunomide 14 mg + GA | Annualized Relapse Rate [ARR]: Poisson Regression Estimates | 0.647 relapses per year |
Secondary
Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)
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 a Mixed-effect model with repeated measures \[MMRM\] on cubic root transformed volume data (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) and 24 weeks
Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + GA | Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) | -0.006 mililiters (mL) | Standard Error 0.036 |
| Teriflunomide 7 mg + GA | Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) | -0.030 mililiters (mL) | Standard Error 0.036 |
| Teriflunomide 14 mg + GA | Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease) | -0.036 mililiters (mL) | Standard Error 0.037 |
Secondary
Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)
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, a Poisson regression model with robust error variance was used (total number of Gd-enhancing T1-lesions as response variable; log-transformed number of scans as offset variable; treatment group, region of enrollment and baseline number of Gd-enhancing T1-lesions as covariates).
Time frame: 24 weeks
Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + GA | Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates) | 0.367 lesions per scan |
| Teriflunomide 7 mg + GA | Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates) | 0.109 lesions per scan |
| Teriflunomide 14 mg + GA | Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates) | 0.171 lesions per scan |
Secondary
Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan
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: 24 weeks
Population: All randomized and treated participants; Participants were included in the treatment group according to the drug actually received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + GA | Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan | 0.063 mililiters per scan |
| Teriflunomide 7 mg + GA | Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan | 0.028 mililiters per scan |
| Teriflunomide 14 mg + GA | Cerebral MRI Assessment: Volume of Gd-enhancing T1-lesions Per Scan | 0.017 mililiters per scan |
Secondary
Pharmacokinetic [PK]: Teriflunomide Plasma Concentration
Plasma concentrations of teriflunomide were measured using validated liquid chromatography-tandem mass spectrometry methods.
Time frame: 24 weeks
Population: All randomized and treated participants who had at least one PK sample. Participants were included in the treatment group according to the drug actually received.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo + GA | Pharmacokinetic [PK]: Teriflunomide Plasma Concentration | 23.443 micrograms/mililiter (μg/mL) | Standard Deviation 10.917 |
| Teriflunomide 7 mg + GA | Pharmacokinetic [PK]: Teriflunomide Plasma Concentration | 46.992 micrograms/mililiter (μg/mL) | Standard Deviation 32.154 |