Evaluation of Tolerance and Pharmacokinetic Profile of High Doses of Favipiravir in Healthy Volunteers

NCT06024421 | Recruiting Phase 1 DMC

• 2 other identifiers: C18-472022-502871-49-00
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Infectious Disease; Pharmacology

Keywords

healthy volunteer; dose escalation; tolerance; pharmacokinetics; favipiravir

Outcome Measures

Primary Outcomes (1)

• 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.

  Months 6

Secondary Outcomes (3)

• Plasma concentration of favipiravir

  Day 1 (Hour 0; Hour 0.5 ; Hour 1; Hour 2; Hour 5; Hour 8), Day 3 (Hour 0 ; Hour 0.5; Hour 2), Day 7 (Hour 0; Hour 0.5 ; Hour 1; Hour 2; Hour 5; Hour 8), Day 10 (Hour 0), Day 14 (Hour 0; Hour 0.5 ; Hour 1; Hour 2; Hour 5; Hour 8), Day 15 (Hour 0)

• Genetic

  Days 1

• Sperm pharmacology

  Day 14, day 28

Study Arms (6)

level 1: experimental

EXPERIMENTAL

D1: 2400 mg BID; D2 to D13: 1600 mg BID and D14: 1600 mg in the morning

Drug: favipiravir

level 2: experimental

EXPERIMENTAL

D1: 2400 mg BID; D2 to D13: 2000 mg BID and D14: 2000 mg in the morning

Drug: favipiravir

level 3: experimental

EXPERIMENTAL

D1: 2400 mg BID; D2 to D13: 2400 mg BID andD14: 2400 mg in the morning

Drug: favipiravir

level 1: placebo

PLACEBO COMPARATOR

D1: 2400 mg BID; D2 to D13: 1600 mg BID and D14: 1600 mg in the morning

Drug: Placebo

level 2: placebo

PLACEBO COMPARATOR

D1: 2400 mg BID; D2 to D13: 2000 mg BID and D14: 2000 mg in the morning

Drug: Placebo

level 3: placebo

PLACEBO COMPARATOR

D1: 2400 mg BID; D2 to D13: 2400 mg BID andD14: 2400 mg in the morning

Drug: Placebo

Interventions

favipiravir DRUG

Light yellow, film-coated tablet, each containing 200 mg of favipiravir

level 1: experimental; level 2: experimental; level 3: experimental

Placebo DRUG

Light yellow, film-coated tablet

level 1: placebo; level 2: placebo; level 3: placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• Blood chemistry:
• Kalemia, Calcemia, Prothrombin rate (PT), Activated partial thromboplastin time (APTT): values within laboratory normal;
• ALT, ASAT, Uricemia: values below the upper limit of the laboratory normal;
• Other biological results (Blood count; Natremia; Phosphoremia; Chloremia; Fasting blood glucose; Gamma glutamyl transpeptidase; Urea; Total bilirubin; Creatinine; CPK; Lactate dehydrogenase; Albuminemia; Proteinemia; Triglycerides; C-reactive protein; Albumin/Globulin ratio; Alkaline phosphatase) with no clinically significant abnormality.
• NB: A parameter outside the usual values considered clinically significant may, at the investigator's discretion, be tested a second time on another sample taken outside of a visit planned in the protocol before the initiation of the experimental drug.
• Urine dipstick (biochemistry: leukocyturia, proteinuria and hematuria) without clinically significant abnormality;
• Urine tox screen negative (amphetamines/metamphetamines, barbiturates, benzodiazepines, cannabis, cocaine, opiates);
• Ability to take the investigational drug orally and adherence to the dosage of the investigational drug;
• Acceptance and signing of the informed consent;
• Membership in a social security plan or beneficiary of such a plan;
• Adherence to lifestyle considerations (see section 5.5) during participation in this research.

You may not qualify if:

• History of gout or current treatment for gout or hyperuricemia
• Treatment with pyrazinamide or any other drug known to induce hyperuricemia
• History of hypersensitivity reaction to a nucleoside analog targeting viral RNA polymerase
• Known hypersensitivity to any of the components (favipiravir or placebo)
• Pregnant or breastfeeding women
• For men: history of vasectomy or known history of infertility.
• Refusal of the subject to complete all the visits, clinical and paraclinical examinations planned by the study
• On ECG: PR \>200ms, QRS \>100ms QTc \>450ms and morphological appearance of abnormal repolarization
• PAS \<100 mmHg
• Any history or active cardiovascular, pulmonary, intestinal, hepatic, renal, metabolic, hematologic, neurologic, bone, joint, muscular, psychiatric, systemic, ocular, gynecologic, andrologic, or infectious disease (including active HIV, HCV, or HBV infection), or any acute condition, which in the judgment of the investigator could be detrimental to the volunteer and/or interfere with or limit the protocol evaluation and data analysis
• Personal or family history of long QT syndrome, torsades de pointes or sudden death
• Patient with severe hepatic impairment
• Gastrointestinal pathology such as ileus, colitis or enterocolitis
• Treatment with another investigational drug or other investigational procedure (clinical trial, clinical investigation of a medical device, category 1 or 2 research involving humans);
• A person who is subject to a legal protection measure (safeguard of justice, curatorship, guardianship);

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead
• FUJIFILM Toyama Chemical Co., Ltd.: collaborator

Study Sites (1)

University Hospital Bichat - Claude Bernard

Paris, 75018, France

RECRUITING

MeSH Terms

Conditions

Communicable Diseases

Interventions

favipiravir

Condition Hierarchy (Ancestors)

Infections; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Denis MALVY

  CHU de Bordeaux & INSERM, Université de Bordeaux, France

  STUDY CHAIR

• Xavier DUVAL

  APHP Hôpital Bichat Claude Bernard

  PRINCIPAL INVESTIGATOR

• Jean-Jacques KILADJIAN

  INSERM Pôle Recherche Clinique

  STUDY DIRECTOR

Central Study Contacts

Cedric LAOUNAN

CONTACT

+33 1 40 25 79 31; cedric.laouenan@inserm.fr

Philippine ELOY

CONTACT

+33 1 40 25 79 31; philippine.eloy@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Active and placebo will not be visually distinguishable. Packaging and labeling of active and placebo tablets will be done in such a way as to not allow unblinding without access to the randomization list or the investigational drug unit list.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Dose-escalation trial

Study Record Dates

• First Submitted: July 7, 2023
• First Posted: September 6, 2023
• Study Start: May 14, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-02

Locations

FR (1)