An Extension Study of LAQ/5062 Exploring the Long Term Safety, Tolerability and Clinical Effect Parameters During the Disease
Condition: Relapsing Remitting Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Intervention: Laquinimod; Placebo
Intervention description: Laquinimod tablets/capsules will be administered as per the dose and schedule specified in the respective arms.; Placebo matching to laquinimod will be administered as per the dose and schedule specified in the respective arms.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking description: Blinding performed by interactive voice response system (IVRS) and relevant only to the first period of the extension. General medical evaluations will be assessed separately from neurological assessment evaluations by two different neurologists/ physicians. Magnetic resonance imaging (MRI) scan evaluation will be performed at a central reading center by staff that does not have access to the clinical data.
Enrollment: 257.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No

Summary:

      This is a multinational, multicenter, randomized, double-blind, parallel-group active
      extension of LAQ/5062 study (NCT00349193), assessing the tolerability, safety and efficacy of
      two doses (0.3 mg and 0.6 mg) of laquinimod, orally administered in participants with
      relapsing remitting multiple sclerosis (RRMS), followed by an open-label phase of laquinimod
      0.6 mg daily. This study is LAQ/5063 (i.e., double-blind extension) and LAQ/5063 OL (i.e.,
      subsequent open-label extension). - The first period of the extension study is an active,
      double-blind period. Participants from the active treatment arms in LAQ/5062 continue their
      assigned treatment in blinded fashion. Participants who were assigned to placebo treatment in
      LAQ/5062 are equally randomized in blinded-fashion to laquinimod 0.6 mg or laquinimod 0.3 mg.
      - Once termination visit of LAQ/5063 active double-blind phase (completion of the full 36
      weeks or as requested by the Sponsor) is performed, all participants continue on laquinimod
      0.6 mg daily as an open-label intervention. The open-label period continues as long as the
      Sponsor continues the development of laquinimod 0.6 mg for RRMS or early discontinuation.
    

Eligibility criteria:

        Inclusion Criteria - Participants must have completed the 36 weeks of treatment (completion
        of the full 36 weeks or as requested by the Sponsor) of the active double-blind phase. -
        Women of childbearing potential (for example, women who were not postmenopausal or
        surgically sterilized) must have practiced 2 acceptable methods of birth control for the
        duration of the study and until 30 days after the last dose of study medication (acceptable
        methods of birth control in this open-label extension phase included intrauterine devices,
        barrier methods [condom or diaphragm with spermicide], and hormonal methods of birth
        control [for example, oral contraceptive, contraceptive patch, and long-acting injectable
        contraceptive]). - Participants must have been willing and able to comply with the protocol
        requirements for the duration of LAQ/5063 OL. - Participants must have given signed,
        written informed consent prior to entering LAQ/5063 OL. - For the 36 months further
        extension: Participants must have completed the 24 months of treatment of the first period
        of the open label phase. Exclusion Criteria - For the 36 month further extension: Premature
        discontinuation from LAQ/5063 OL phase prior to completion of 24 months of treatment
        period. - Pregnancy or breastfeeding. - Participants with clinically significant or
        unstable medical or surgical condition, detected or worsened during the active double-blind
        phase of LAQ/5063, which would have precluded safe and complete study participation. - Use
        of experimental drugs, immunosuppressive drugs, and/or participation in clinical studies
        within the period from termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. -
        Previous treatment with immunomodulators with the exception of laquinimod (including
        interferon [IFN] 1a and 1b, glatiramer acetate, and intravenous [IV] immunoglobulin) within
        2 months prior to entering the open-label phase for those subjects who had a time gap
        between termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. - Use of
        corticosteroids within 30 days prior to entering the open-label phase, except for IV
        methylprednisolone 1 grams/day for a maximum of 3 days, in the period from termination of
        LAQ/5063 active double-blind phase to LAQ/5063 OL. - Use of potent inhibitors of cytochrome
        P3A4 (CYP3A4) within 2 weeks prior to LAQ/5063 OL and/or use of fluoxetine 1 month prior to
        entering LAQ/5063 OL, in the period from termination of LAQ/5063 active double-blind phase
        to LAQ/5063 OL. - Use of the following substrates of cytochrome P1A2 (CYP1A2): theophylline
        and/or warfarin within 2 weeks prior to entering LAQ/5063 OL, in the period from
        termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. - Use of amiodarone in
        the period from termination of LAQ/5063 active double-blind phase to LAQ/5063 OL. -
        Following the switch to new formulation (capsules), hypersensitivity to mannitol,
        meglumine, or sodium stearyl fumarate.