NCT02091310

Phase I Study to Evaluate the Effect of GFT505 on QT/QTc Interval in Healthy Volunteers

A Two-part Phase I Study Composed of a Randomized, Double-blind, 4-parallel Group Study to Evaluate the Effect of Multiple Oral Doses of GFT505 on the QT/QTc Interval Compared to Placebo With Moxifloxacin (400 mg in Single Oral Dose) as a Positive Control, in Healthy Male and Female Volunteers, Preceded by a Double-blind, Placebo-controlled, Safety, Tolerability and Pharmacokinetic Study in Healthy Male Volunteers in Order to Define the Supra-therapeutic GFT505 Dose in a Multiple Dosing Regimen.

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 200 (actual)
• Sponsor: Genfit · Industry
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

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.

Conditions

• Healthy Volunteers

Interventions

Type	Name	Description
DRUG	Placebo
DRUG	GFT505
DRUG	Moxifloxacin 400 mg

Timeline

• Start date: 2014-02-01
• Primary completion: 2014-12-01
• Completion: 2015-02-01
• First posted: 2014-03-19
• Last updated: 2015-03-10

Locations

1 site across 1 country: France