FAVIDOSE trial is a Phase I randomized, double blind controlled, monocentric, dose escalation clinical trial. The primary purpose of this trial is to evaluate tolerance of high doses of favipiravir for 14 days in healthy volunteers. This trial also looks to characterize favipiravir pharmacokinetics in blood and favipiravir levels in sperm. A pharmacogenetics analysis will be conducted in an attempt to identify genetic variants of metabolism and transport enzymes of favipiravir to explain the inter-individual variability of pharmacokinetic parameters of favipiravir.
Three sequential dose levels including distinctive participants:
* level 1: D1: 2400 mg BID; D2 to D13: 1600 mg BID and D14: 1600 mg in the morning; * level 2: D1: 2400 mg BID; D2 to D13: 2000 mg BID and D14: 2000 mg in the morning; * level 3: D1: 2400 mg BID; D2 to D13: 2400 mg BID andD14: 2400 mg in the morning.
Three study groups of maximum of 8 participants, 6 receiving favipiravir and 2 receiving placebo per dose level, three dose levels proposed. Seven additional participants with the same follow up will be included and randomized (6:1 ratio) at the maximum tolerated dose level to allow a satisfactory accurate characterization of pharmacokinetics and pharmacogenetics of favipiravir and their determinants (maximum 39 participants in total, taking into account 8 participants - 2 per dose level - replaced because loss of follow-up before the end of treatment).
Man between 50 and 75 years old without any desire to have children or woman between 18 and 75 years old ;
Subject considered healthy after a thorough general examination (questioning, physical examination);
For men: acceptance of semen collection by masturbation;
For men: acceptance of condom use from initiation of the investigational drug until 1 month after stopping the investigational drug;
Concomitant use or within 15 days prior to inclusion of another QT/QTc prolonging drug or drugs that may disrupt electrolyte levels, among others: loop diuretics, thiazide diuretics and related drugs (see list www.crediblemeds.org)
History of amiodarone use within 6 months prior to inclusion
History of gout or current treatment for gout or hyperuricemia
Treatment with pyrazinamide or any other drug known to induce hyperuricemia
Parallel
favipiravir
DrugLight yellow, film-coated tablet, each containing 200 mg of favipiravir
Placebo
DrugLight yellow, film-coated tablet
6
Treatment groupsSee each treatment group below.
Tolerance
Tolerance of high doses of favipiravir, defined by the number of participants with at least one adverse medical event considered as related to favipiravir (AER)-as determined and validated by the sponsor- clinical stage 3 or 4 according to the CTCAE (v5.0) not found at inclusion at same level and biological AER de stage 3 or 4 not found at inclusion in the same level. AER are collected daily until D15 and at D21 and D28, as well as at M3 and M6 for participating men. D1 is the first day of favipiravir or placebo intake.
Plasma concentration of favipiravir
Construction of the pharmacokinetic model and the estimation of its parameters will be realized by a population pharmacokinetic analysis integrating all available data on plasma concentration.
Genetic
Genetic variants associated with favipiravir exposure. Targeted genotyping of variants of the gene encoding the enzyme responsible for transport and metabolism of favipiravir (aldehyde deshydrogenase) will be performed.
Sperm pharmacology
For participating men: favipiravir concentration in sperm at D14 and D28.
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Institut National de la Santé Et de la Recherche Médicale, France
Lead sponsor
FUJIFILM Toyama Chemical Co., Ltd.
Collaborator
