Evaluating high doses of favipiravir in healthy volunteers

EVALUATION DE LA TOLERANCE ET DU PROFIL PHARMACOCINETIQUE DE DOSES ELEVEES DE FAVIPIRAVIR CHEZ LE VOLONTAIRE SAIN

This study is testing how well healthy volunteers can tolerate high doses of favipiravir over two weeks to learn more about its safety and how the body processes it.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Institut National de la Santé Et de la Recherche Médicale, France (Government)
• Locations: 1 site (Paris)
• Trial ID: NCT06024421 on ClinicalTrials.gov

What this trial studies

The FAVIDOSE trial is a Phase I randomized, double-blind, controlled clinical trial designed to assess the tolerance and pharmacokinetic profile of high doses of favipiravir over a 14-day period in healthy volunteers. Participants will be assigned to one of three sequential dose levels, with a total of six receiving favipiravir and two receiving a placebo in each group. The study will also analyze favipiravir levels in blood and sperm, along with conducting pharmacogenetic analyses to identify genetic factors influencing drug metabolism and transport. This approach aims to provide insights into the drug's safety and efficacy at higher doses.

Who should consider this trial

Good fit: Ideal candidates for this study are healthy men aged 50 to 75 or women aged 18 to 75 who are not planning to conceive.

Not a fit: Patients who are not healthy or those who are pregnant or planning to become pregnant may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could enhance the understanding of favipiravir's safety and pharmacokinetics, potentially leading to improved treatment protocols for infectious diseases.

How similar studies have performed: While this study focuses on high doses of favipiravir, similar pharmacokinetic studies have shown promise in understanding drug tolerance and metabolism, making this approach both relevant and potentially beneficial.

Eligibility criteria

Inclusion Criteria:

1. Man between 50 and 75 years old without any desire to have children or woman between 18 and 75 years old ;
2. Subject considered healthy after a thorough general examination (questioning, physical examination);
3. For men: acceptance of semen collection by masturbation;
4. For men: acceptance of condom use from initiation of the investigational drug until 1 month after stopping the investigational drug;
5. For women of childbearing potential: effective contraceptive method combining two methods of contraception (one female contraceptive method combined with male condom use) from the inclusion visit until 1 month after discontinuation of the investigational drug;
6. 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.
7. Urine dipstick (biochemistry: leukocyturia, proteinuria and hematuria) without clinically significant abnormality;
8. Urine tox screen negative (amphetamines/metamphetamines, barbiturates, benzodiazepines, cannabis, cocaine, opiates);
9. Ability to take the investigational drug orally and adherence to the dosage of the investigational drug;
10. Acceptance and signing of the informed consent;
11. Membership in a social security plan or beneficiary of such a plan;
12. Adherence to lifestyle considerations (see section 5.5) during participation in this research.

Exclusion Criteria:

1. 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)
2. History of amiodarone use within 6 months prior to inclusion
3. History of gout or current treatment for gout or hyperuricemia
4. Treatment with pyrazinamide or any other drug known to induce hyperuricemia
5. History of hypersensitivity reaction to a nucleoside analog targeting viral RNA polymerase
6. Known hypersensitivity to any of the components (favipiravir or placebo)
7. Pregnant or breastfeeding women
8. For men: history of vasectomy or known history of infertility.
9. Refusal of the subject to complete all the visits, clinical and paraclinical examinations planned by the study
10. On ECG: PR \>200ms, QRS \>100ms QTc \>450ms and morphological appearance of abnormal repolarization
11. PAS \<100 mmHg
12. 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
13. Personal or family history of long QT syndrome, torsades de pointes or sudden death
14. Patient with severe hepatic impairment
15. Gastrointestinal pathology such as ileus, colitis or enterocolitis
16. Treatment with another investigational drug or other investigational procedure (clinical trial, clinical investigation of a medical device, category 1 or 2 research involving humans);
17. A person who is subject to a legal protection measure (safeguard of justice, curatorship, guardianship);
18. Person placed in administrative detention;
19. Person who, in the judgment of the investigating physician, may be non-observant during the study, or unable to communicate due to a language barrier or mental disorder
20. Person who cannot be contacted in an emergency
21. Person with at least one first-degree relative from East Asia or Southeast Asia.

Secondary Exclusion Criteria

Participants with at least one of the following criteria will not start the experimental treatment at D1 if they are already randomized:

1. Positive nasopharyngeal antigen test for SARS-CoV-2 at D1 (prior to treatment initiation)
2. Blood potassium levels outside the normal laboratory range within 8 days prior to treatment initiation (D1)
3. ECG: PR \>200ms, QRS \>100ms QTc \>450ms and morphological appearance of abnormal repolarization on Day 1
4. Positive pregnancy test on Day 1 (before initiation of treatment)

Where this trial is running

Paris

• University Hospital Bichat - Claude Bernard — Paris, France (Recruiting)

Study contacts

• Principal investigator: Xavier DUVAL — APHP Hôpital Bichat Claude Bernard
• Study coordinator: Cedric LAOUNAN

Conditions Infectious Disease; Pharmacology; healthy volunteer; dose escalation; tolerance; pharmacokinetics; favipiravir