An Open Label, Randomised, Repeat Dose Study to Assess the Pharmacokinetic Performance of Five Ezogabine/Retigabine Modified Release (MR) Formulations at Steady State Compared to the Immediate Release (IR) Formulation.
Condition: Epilepsy
MeSH terms: Epilepsy
Study type: Interventional
Phase: Phase 1

Summary: 
      This is an open-label, single centre, repeat dose, up- titration study in healthy male and
      female subjects to assess the pharmacokinetic (PK) performance of five prototypes of
      ezogabine modified release tablet formulations.

      The study will consist of a screening period, a treatment phase (consisting of a titration
      phase, bioavailability phase and food effect phase) and a post-treatment follow-up visit. The
      study duration from screening to follow up will be approximately 7 weeks. No study procedures
      will start before informed consent is obtained. Subjects will remain in the clinical unit for
      the duration of the treatment period (35 days).

      Subjects will receive repeat doses of ezogabine for up to 34 days starting at a dose of 100
      mg IR TID (300mg TDD) with a standard meal (to be consumed 30 min prior to dosing) for Days
      1-3, on days 4-6 subjects will receive 150mg IR TID (450mg TDD). On Day 7 through to the end
      of the study subjects will receive ezogabine (Mr or IR) at a dose of 600mgTDD.

      On Day 7 subjects will enter into a 6-way cross over period to investigate the 5 MR
      formulations being tested (each at 300mg BID) and the single IR formulation (at 200mg TID).
      Subjects will receive each formulaition for 4 days and blood samples for pharmacokinetic
      analysis will be collected up to 24 hours post dose on each 4th day (PK days).

      On Day 31 subjects will enter into a food effect phase to investigate the 5 MR formulations
      being tested (each at 600mg QD). Subjects in this period will have a PK day on Day 33
      (following a standard breakfast), and on Day 34 (following a high fat breakfast) to
      investigate a food effect on the PK profile of ezogabine.
    


Intervention name(s): Investigational Medicinal Product (MR1); Investigational Medicinal Product (MR2); Investigational Medicinal Product (MR3); Investigational Medicinal Product (MR4); Investigational Medicinal Product (MR5); Investigational Medicinal Product (IR)
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Ezogabine MR1 at a dose strength of 300 mg will be orally administered with approximately 250 milliliter (mL) of water to group A subjects during the bioavailability phase. For the food effect phase subjects in group G will be orally administered MR1 tablets at a dose strength of 600 mg.; Ezogabine MR2 at a dose strength of 300 mg will be orally administered to group B subjects with approximately 250 mL of water during the bioavailability phase. For the food effect phase subjects in group H will be orally administered MR2 tablets at a dose strength of 600 mg.; Ezogabine MR3 will be orally administered with approximately 250 mL of water to group C subjects during the bioavailability phase. For the food effect phase subjects in group I will be orally administered MR3 tablets at a dose strength of 600 mg.; Ezogabine MR4 will be orally administered with approximately 250 mL of water to group D subjects during the bioavailability phase. For the food effect phase subjects in group J will be orally administered MR4 tablets at a dose strength of 600 mg.; Ezogabine MR5 will be orally administered with approximately 250 mL of water to group E subjects during the bioavailability phase. For the food effect phase subjects in group K will be orally administered MR5 tablets at a dose strength of 600 mg.; Ezogabine IR at dose strengths of 50 mg and 200 mg will be orally administered with approximately 250 mL of water.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Healthy Volunteers