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

Launched by INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE, FRANCE · Aug 31, 2023

Keywords

ClinConnect Summary

The FAVIDOSE trial is a clinical study designed to test how well healthy volunteers tolerate high doses of a medication called favipiravir over a 14-day period. Researchers want to understand how the drug behaves in the body and how it might affect sperm levels. The study will involve giving different groups of participants varying doses of favipiravir, while some will receive a placebo (a dummy pill with no medication) to compare the results. The trial aims to include men aged 50 to 75 who are healthy and willing to participate, as well as women aged 18 to 75 who are also healthy and can use effective birth control during the study.

Participants in the trial can expect to take the medication twice daily for the first few days and then once daily for the remainder of the study. They will undergo regular check-ups, including blood tests and, for men, semen collection. It’s important for potential participants to know that there are specific health criteria they must meet to be included in the study, such as not having certain medical conditions or taking specific medications. Overall, this trial is crucial for understanding how favipiravir works in the body, which could help in treating infectious diseases in the future.

Gender

ALL

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)