Phase I Study to Evaluate the Effect of GFT505 on QT/QTc Interval in Healthy Volunteers
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      In accordance with International Conference on Harmonisation (ICH) E14 guidelines, this Phase
      I thorough QT (TQT) study will assess the arrhythmogenic potential of GFT505, by evaluating
      its effect on QT/QTc prolongation in healthy male and female subjects. According to the
      guidelines, such studies should typically be performed at the expected therapeutic dose and a
      supra-therapeutic dose that is 3-4-fold higher than the therapeutic dose.

      GFT505 has previously been tested at 240 mg/d in 14-day multiple administration to healthy
      overweight subjects (study GFT505-111-7), and both safety and tolerability were very good.
      However, this dose corresponds to only 2-fold the expected therapeutic dose of 120 mg/d.
      Therefore, the current TQT study will be preceded by a multiple ascending dose study in which
      the safety and tolerability of 2 dose levels of GFT505 (300 and 360 mg) corresponding to 2.5
      and 3 times the expected therapeutic dose will be evaluated. The highest dose level for which
      safety and tolerability are considered satisfactory will be the supra-therapeutic dose used
      in the TQT study.
    

Detailed description: 
      The present trial is split into two successive parts:

        -  Study Part I is a double-blind, randomized, placebo-controlled study designed to obtain
           safety, tolerability and pharmacokinetic (PK) data after 14-day multiple oral
           administrations of once-daily increasing doses of GFT505 (300 and 360 mg) in healthy
           male subjects. The starting dose of 300 mg/day has been selected on the basis of the
           results of previous clinical trials and corresponds to the highest dose given in healthy
           subjects according to a single dose regimen (study GFT505-111-7). A total of 24 male
           subjects will be included, 12 for each cohort (a cohort corresponding to a dose level).
           In each cohort, 9 subjects will receive GFT505 and 3 will receive placebo. A Safety
           Review Committee (SRC) will have a formal meeting after full completion of at least 10
           out of 12 subjects of each dose level to review under blinded conditions all safety data
           and to conclude on the safety and tolerability of a given dose level. Between the first
           and the second dose level, the SRC will give its agreement on the dose escalation, and
           at completion of the second level the SRC will define the supra-therapeutic dose to be
           administered in Study Part II.

        -  Study Part II will be a parallel group, randomized, placebo-controlled study, with
           stratification by gender. The study is designed to investigate the potential impact of
           14-day multiple oral administrations of once-daily GFT505 on QT/QTc prolongation under
           conditions of maximal GFT505 exposure, i.e. by administering the expected therapeutic
           dose of 120 mg/d and a supra-therapeutic dose (defined according to the results of Study
           Part I), to healthy male and female subjects. A single oral dose of 400 mg moxifloxacin
           will be used as a positive control in order to document the sensitivity of the
           experimental conditions. The study treatment administration will be double-blind for
           placebo and GFT505 and open for moxifloxacin. The ECG readings will be performed under
           blinded conditions. A preliminary sample size of 128 subjects to have at least 124
           evaluable subjects has been fixed by formal justification on a theoretical basis. ECG
           data collected during Study Part I will support a formal determination using observed
           data and thus will lead to a final sample size. In all cases, it is anticipated that the
           sample size could not be less than 124 evaluable subjects. Each gender will represent at
           least 40% of the study population. Both sub-groups will be balanced between the 4
           treatment groups.
    

Intervention name(s): Placebo; GFT505; Moxifloxacin 400 mg
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Moxifloxacin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: GFT505; TQT; QT/QTc; Pharmacokinetic; Healthy subjects; Moxifloxacin