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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
123
Film-coated tablet Oral administration
Film-coated tablet Oral administration
Solution in prefilled syringe for subcutaneous injection
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, United States
Sanofi-Aventis Administrative Office
Vienna, Austria
Sanofi-Aventis Administrative Office
Laval, Canada
Sanofi-Aventis Administrative Office
Berlin, Germany
Sanofi-Aventis Administrative Office
Milan, Italy
Sanofi-Aventis Administrative Office
Guildford, United Kingdom
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)
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)
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)
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
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
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
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
Pharmacokinetic [PK]: Teriflunomide Plasma Concentration
Plasma concentrations of teriflunomide were measured using validated liquid chromatography-tandem mass spectrometry methods.
Time frame: 24 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.