Long Term Safety of Teriflunomide When Added to Interferon-Beta or Glatiramer Acetate in Patients With Multiple Sclerosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00811395
First received: December 18, 2008
Last updated: December 18, 2012
Last verified: December 2012
Results First Received: October 3, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Multiple Sclerosis
Interventions: Drug: Teriflunomide
Drug: Placebo (for teriflunomide)
Drug: Interferon-β [IFN-β]
Drug: Glatiramer Acetate [GA]

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

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.


Reporting Groups
  Description
Placebo + IFN-β Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 7 mg + IFN-β Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 14 mg + IFN-β Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β]
Placebo + GA Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 7 mg + GA Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 14 mg + GA Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate [GA]

Participant Flow for 2 periods

Period 1:   Initial Treatment (PDY6045 or PDY6046)
    Placebo + IFN-β     Teriflunomide 7 mg + IFN-β     Teriflunomide 14 mg + IFN-β     Placebo + GA     Teriflunomide 7 mg + GA     Teriflunomide 14 mg + GA  
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 2:   Extension Treatment
    Placebo + IFN-β     Teriflunomide 7 mg + IFN-β     Teriflunomide 14 mg + IFN-β     Placebo + GA     Teriflunomide 7 mg + GA     Teriflunomide 14 mg + GA  
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  
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



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo + IFN-β Placebo (for teriflunomide) once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 7 mg + IFN-β Teriflunomide 7 mg once daily concomitantly with interferon-β [IFN-β]
Teriflunomide 14 mg + IFN-β Teriflunomide 14 mg once daily concomitantly with interferon-β [IFN-β]
Placebo + GA Placebo (for teriflunomide) once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 7 mg + GA Teriflunomide 7 mg once daily concomitantly with Glatiramer Acetate [GA]
Teriflunomide 14 mg + GA Teriflunomide 14 mg once daily concomitantly with Glatiramer Acetate [GA]
Total Total of all reporting groups

Baseline Measures
    Placebo + IFN-β     Teriflunomide 7 mg + IFN-β     Teriflunomide 14 mg + IFN-β     Placebo + GA     Teriflunomide 7 mg + GA     Teriflunomide 14 mg + GA     Total  
Number of Participants  
[units: participants]
  41     37     38     40     42     41     239  
Age, Customized [1]
[units: participants]
             
<38 years     17     9     15     11     12     13     77  
>=38 years     24     28     23     29     30     28     162  
Gender  
[units: participants]
             
Female     31     25     25     31     33     33     178  
Male     10     12     13     9     9     8     61  
Region of Enrollment [2]
[units: participants]
             
Europe     28     25     24     22     22     22     143  
North America     13     12     14     18     20     19     96  
[1] Baseline characteristics before randomization in the initial study (PDY6045 or PDY6046)
[2]

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

North America: Canada and United States




  Outcome Measures
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1.  Primary:   Overview of Adverse Events [AE]   [ 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) ]

2.  Primary:   Overview of AE With Potential Risk of Occurence   [ 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) ]

3.  Primary:   Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA]   [ 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) ]

4.  Secondary:   Annualized Relapse Rate [ARR]: Poisson Regression Estimates   [ Time Frame: 48 weeks ]

5.  Secondary:   Overview of 12-week Sustained Disability Progression   [ Time Frame: 48 weeks ]

6.  Secondary:   Time to 12-week Sustained Disability Progression: Kaplan-Meier Estimates of the Rate of Disability Progression at Timepoints   [ Time Frame: 48 weeks ]

7.  Secondary:   Cerebral Magnetic Resonance Imaging [MRI] Assessment: Change From Baseline in Total Lesion Volume (Burden of Disease)   [ Time Frame: baseline (before randomization in PDY6045 or PDY6046) and 48 weeks ]

8.  Secondary:   Cerebral MRI Assessment: Number of Gd-enhancing T1-lesions Per Scan (Poisson Regression Estimates)   [ Time Frame: 48 weeks ]

9.  Secondary:   Cerebral MRI Assessment: Total Volume of Gd-enhancing T1-lesions Per Scan   [ Time Frame: 48 weeks ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Trial Transparency Team
Organization: sanofi-aventis
e-mail: Contact_US@sanofi-aventis.com


Publications of Results:

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00811395     History of Changes
Other Study ID Numbers: LTS6047, HMR1726D/2005, 2007-003997-24
Study First Received: December 18, 2008
Results First Received: October 3, 2012
Last Updated: December 18, 2012
Health Authority: Canada: Health Canada
United States: Food and Drug Administration