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

• Status: Completed
• Trial end date: 2015-02-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Genfit
• Collaborators: CardiaBase; Eurofins Optimed; PHINC DEVELOPMENT
• Treatments: Fluoroquinolones; Moxifloxacin; Norgestimate, ethinyl estradiol drug combination

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

• 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

• For women: Positive pregnancy test at screening or on Day -2; Pregnancy or trying to become pregnant; Breastfeeding

• 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.