A Drug Interaction Study of the Pharmacokinetics of Topiramate and FLUNARIZINE When Given Together or Separately
Condition: Human Volunteers; Migraine
MeSH terms: Migraine Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      The primary purpose of this open-label study is to determine if concomitant therapy with
      topiramate and flunarizine has any effect on the pharmacokinetics of either drug. Safety will
      be assessed for all subjects, for the entire duration of the study.
    

Detailed description: 
      This is a multicenter, randomized open-label study to be conducted in 2 groups of subjects.
      Group 1 will consist of migraine patients to be recruited at multiple sites and Group 2 will
      include healthy subjects at a single study center. In Group 1 a total of 36 subjects will be
      enrolled with a target of having 24 subjects complete the study. In Group 2, a total of 28
      healthy subjects will be enrolled so that at least 24 will complete the trial. Group 1 will
      include patients under treatment for migraine prophylaxis with any dose of flunarizine for at
      least 4 weeks prior to the 6-week run-in phase. Once selected, patients will enter a 6-week
      run-in phase in which they will receive 5mg of flunarizine every evening. Following this
      run-in phase, patients will continue on flunarizine and be randomized into 2 subgroups of
      equal size; Subgroup 1a will consist of patients being treated with topiramate and
      flunarizine and Subgroup 1b, the control group, where patients will only be receiving
      flunarizine treatment. Patients in Group 1 (Subgroups 1a and 1b) will commence initial
      confinement (Day 1) after completing the 6-week run-in phase. All these patients must have a
      history of migraine according to IHS1 criteria for at least 1 year prior to study entry. For
      both Groups 1 and 2 dropouts will be replaced to ensure the required number of
      patients/subjects of each sex to complete the study. Safety will be assessed by studying the
      incidence and severity of treatment-emergent adverse events and abnormal findings of other
      safety evaluations. Changes in clinical laboratory test and vital sign results from Baseline
      to End of Study or early termination will be evaluated.

      In Group 1: 5 mg flunarizine every 24 hours (at 8:00 p.m.), beginning on Day -42 for 6 weeks,
      through Day -1. Patients will continue to receive this dose from Days 1 through 81. Group 1a:
      On Day 4 Topiramate dose titrated from 25 mg BID to 75 mg (25 mg am and 50 mg pm) by Day 19
      and 50 mg BID by Day 26 - Day 81. Group 1b continue on Flunarizine only. Group 2: Topiramate
      beginning Day 2 titration from 25 mg BID to 50 mg BID by Day 5 through 18. 5mg Flunarizine
      daily starting Day 12- Day 18.
    

Intervention name(s): Topiramate; flunarizine
Intervention type(s): Drug
Intervention MeSH terms: Topiramate; Flunarizine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Healthy volunteers; drug interaction; Flunarizine; Topiramate; Migraine