TMC278-TiDP6-C152: A Study to Assess the Effects of TMC278 and Efavirenz (EFV) on the QT/QTc Interval (Heart Conduction and Heart Rhythm) in Healthy Volunteers.
Condition: Human Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a study to evaluate the effect of TMC278 25 mg daily on the QT/QTc interval (heart
      conduction and heart rhythm) in healthy volunteers. In a separate panel of healthy
      volunteers, the effect of efavirenz (EFV) 600 mg daily on the QT/QTc interval will be
      evaluated.
    

Detailed description: 
      This is a trial to evaluate the effect of TMC278 25 mg daily on the QT/QTc interval (heart
      conduction and heart rhythm) in healthy volunteers. In a separate panel of healthy
      volunteers, the effect of efavirenz (EFV) 600 mg daily on the QT/QTc interval will be
      evaluated. TMC278 is being investigated as a treatment for HIV-1 infection. In one panel, the
      effect of TMC278 at steady-state on the QT/QTc interval in healthy volunteers will be
      evaluated in a double-blind (neither the doctor nor the patient know if the patient is
      getting active drug or placebo), randomized (study drug assigned by chance), placebo
      controlled and positive controlled 3-way crossover design. One dose regimen of 25 mg daily of
      TMC278 will be tested for 11 days. In a second session, a single dose of 400 mg of
      moxifloxacin will be used as a positive control to assess trial sensitivity. A placebo
      session will be included as a reference. In a separate panel, the effect of EFV at
      steady-state on the QT/QTc interval in healthy volunteers will be evaluated in a
      double-blind, randomized, placebo controlled 2-way crossover design. One dose regimen of 600
      mg daily of EFV will be tested for 11 days. Similar to the TMC278 panel, a placebo session
      will be included as a reference. The overall trial population will consist of 120 healthy
      volunteers of which at least 30% and no more than 50% are female and of which at least 20%
      are non-Hispanic Caucasians. Patients will be randomized in a 1:1 ratio to either the TMC278
      panel or the EFV panel. The randomization between the 2 panels will be stratified by gender
      and ethnicity and the randomization within each panel will be stratified by gender. Each
      patient in the TMC278 panel will receive in 3 sessions in a random order: TMC278 25 mg daily
      on Day 1-11 and moxifloxacin placebo q.d. on Day 11 (Treatment A), TMC278 placebo daily on
      Day 1-11 and moxifloxacin placebo q.d. on Day 11 (Treatment B), and TMC278 placebo daily on
      Day 1-11 and moxifloxacin 400 mg q.d. on Day 11 (Treatment C). All intakes of TMC278,
      moxifloxacin, TMC278 placebo and moxifloxacin placebo will be under fed conditions and will
      take place under supervision in the unit. There will be a washout period of at least 21 days
      between consecutive treatments. Each patient in the EFV panel will receive in 2 sessions in a
      random order: EFV 600 mg daily for 11 days (Treatment D) or EFV placebo q.d. for 11 days
      (Treatment E). All intakes of EFV and EFV placebo will be under fasted conditions and will
      take place under supervision in the unit. There will be a washout period of at least 53 days
      between the 2 treatments. In both the TMC278 and the EFV panels, ECGs will be recorded
      continuously for 24 hours by Holter monitoring on Day -1 and Day 11 of all treatment
      sessions. In addition, for safety monitoring, 12-lead ECGs will be performed at predefined
      time points. Pharmacokinetic samples will be collected on Day -1, Day 9, Day 10, and Day 11,
      within 5 minutes after safety ECG recording or Holter extraction time point, if applicable,
      for the determination of TMC278, moxifloxacin or EFV plasma concentrations, as appropriate.
      Safety and tolerability will be monitored throughout the trial. In the TMC278 Panel, TMC278
      or placebo will be given by mouth on Days 1-11 and Moxifloxican or placebo will be given by
      mouth on Day 11. Patients will return after each washout period for a total of 3 cycles. In
      the EFV Panel, EFV or placebo will be given by mouth on Days 1-11. Patients will return after
      the washout period for a total of 2 cycles.
    

Intervention name(s): TMC278; Moxifloxacin; Efavirenz
Intervention type(s): Drug
Intervention MeSH terms: Moxifloxacin; Efavirenz; Rilpivirine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Diagnostic
Keywords: TMC278-C152; TMC278-TiDP6-C152; Healthy Volunteers; QT/QTc interval