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

NCT02091310 | Completed Phase 1

• 2 other identifiers: GFT505-113-92013-005154-30
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers

Keywords

GFT505; TQT; QT/QTc; Pharmacokinetic; Healthy subjects; Moxifloxacin

Outcome Measures

Primary Outcomes (2)

• Safety parameters such as adverse event monitoring, vital signs, ECG, and clinical laboratory tests (Study Part I)

  To evaluate the safety and tolerability of two dose levels of GFT505 (300 and 360 mg), after multiple dose administration once daily for 14 days in male healthy subjects in order to determine the supra-therapeutic dose to be administered in Study Part II.

  14 days

• Effect on QTcF compared to placebo (Study Part II)

  To evaluate the impact on QTcF of two dose levels (one therapeutic and one supra-therapeutic according to ICH E14) of GFT505, after multiple dose administration once daily for 14 days in healthy male and female subjects compared to placebo and a positive control.

  14 days

Secondary Outcomes (3)

• Pharmacokinetic parameters including Cmax, Tmax, AUCt (Study Part I)

  14 days

• Safety parameters such as adverse event monitoring, vital signs, ECG, and clinical laboratory tests (Study Part II)

  14 days

• Effect on QTcB compared to placebo (Study Part II)

  14 days

Study Arms (7)

Placebo (Study Part I)

PLACEBO COMPARATOR

Hard gelatin capsules, oral administration, 5 or 6 capsules per day before breakfast with a glass of water

Drug: Placebo

GFT505 300 mg (Study Part I)

EXPERIMENTAL

Hard gelatin capsules dosed at 60mg, oral administration, 5 capsules per day before breakfast with a glass of water

Drug: GFT505

GFT505 360 mg (Study Part I)

EXPERIMENTAL

Hard gelatin capsules dosed at 60mg, oral administration, 6 capsules per day before breakfast with a glass of water

Drug: GFT505

Placebo (Study Part II)

PLACEBO COMPARATOR

Hard gelatin capsules, oral administration, 4 to 6 capsules per day before breakfast with a glass of water

Drug: Placebo

GFT505 120 mg (Study Part II)

EXPERIMENTAL

Hard gelatin capsules dosed at 60mg, oral administration, 2 capsules per day plus 2 to 4 capsules of placebo per day before breakfast with a glass of water

Drug: GFT505

GFT505 xx mg (Study Part II)

EXPERIMENTAL

Supra-therapeutic dose: hard gelatin capsules dosed at 60mg, oral administration, 4 to 6 capsules per day before breakfast with a glass of water

Drug: GFT505

Moxifloxacin 400 mg (Study Part II)

ACTIVE COMPARATOR

On days 1 to 13, 4 to 6 placebo capsules per day, then one 400 mg moxifloxacin tablet (Izilox®, Bayer Pharmaceuticals Corporation) administered orally on Day 14

Drug: Moxifloxacin 400 mg

Interventions

Placebo DRUG

Placebo (Study Part I); Placebo (Study Part II)

GFT505 DRUG

GFT505 120 mg (Study Part II); GFT505 300 mg (Study Part I); GFT505 360 mg (Study Part I); GFT505 xx mg (Study Part II)

Moxifloxacin 400 mg DRUG

Moxifloxacin 400 mg (Study Part II)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Part I:
• Healthy males aged 18 to 45 years inclusive
• Body Mass Index (BMI) ≥ 18 ≤ 30 kg/m²
• No clinically relevant abnormalities in blood pressure (BP) or heart rate (HR)
• No clinically relevant abnormalities in 12-lead ECG results
• Part II:
• Healthy males and females aged 18 to 45 years inclusive
• For female subjects of childbearing potential, use of double contraception method
• Body Mass Index (BMI) ≥ 18 ≤ 30 kg/m²
• No clinically relevant abnormalities in blood pressure (BP) or heart rate (HR)
• No clinically relevant abnormalities in 12-lead ECG results

You may not qualify if:

• Part I:
• Evidence of clinically relevant cardiovascular, renal, hepatic, hematological, gastrointestinal, pulmonary, metabolic-endocrine, neurological, urogenital or psychiatric diseases
• A history of risk factors for "Torsades de Pointe" (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
• Any condition requiring regular concomitant medication, including herbal products and over-the-counter (OTC) medication or predicted need of any concomitant medication during the study
• Current drug or alcohol abuse \[including regular alcohol drinking of more than 21 units per week (1 unit = 4 cL spirits or equivalent)\] or a history of drug or alcohol abuse within 1 year before screening
• Current use of nicotine containing products, i.e., more than 5 cigarettes or equivalent/day and the inability to stop using nicotine containing products during confinement in the clinical center
• Use of caffeine containing beverages exceeding 500 mg caffeine/day (5 cups of coffee) and the inability to refrain from the use of caffeine containing beverages during confinement in the clinical center
• Blood donation or loss of significant amount of blood within 2 months prior to the first dosing
• Any other condition that in the opinion of the Investigator would interfere with the evaluation of the results or constitute a health risk for the subject.
• Part II:
• Evidence of clinically relevant cardiovascular, renal, hepatic, hematological, gastrointestinal, pulmonary, metabolic-endocrine, neurological, urogenital or psychiatric diseases
• A history of risk factors for "Torsades de Pointe" (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
• The use of concomitant medications that prolong the QT/QTc interval
• Any condition requiring regular concomitant medication, including herbal products and over-the-counter (OTC) medication or predicted need of any concomitant medication during the study
• Current drug or alcohol abuse \[including regular alcohol drinking of more than 21 units (for male) or 14 units (for female) (1 unit = 4 cL spirits or equivalent)\] or a history of drug or alcohol abuse within 1 year before screening

Sponsors & Collaborators

• Genfit: lead
• Eurofins Optimed: collaborator
• CardiaBase: collaborator
• PhinC Development: collaborator

Study Sites (1)

Eurofins Optimed

Gières, 38610, France

Location

MeSH Terms

Interventions

2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid; Moxifloxacin

Intervention Hierarchy (Ancestors)

Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Rémy Hanf, PhD

  Genfit

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2014
• First Posted: March 19, 2014
• Study Start: February 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: February 1, 2015
• Last Updated: March 10, 2015

Record last verified: 2015-03

Locations

FR (1)