Safety, Tolerability and Pharmacokinetics of RNV-166 in Healthy Male Volunteers

A Randomized, Double-Blind, Placebo-controlled, Single-Ascending-Dose and Multiple-Ascending-Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of RNV-166 in Healthy Male Volunteers

This Phase 1 first-in-human clinical study evaluated the safety, tolerability, and pharmacokinetics of RNV-166 following single ascending dose (SAD) and multiple ascending dose (MAD) administration in healthy participants. Single oral doses of RNV-166 ranging from 200 mg to 1600 mg were assessed, including evaluation under fed (high-fat meal) conditions to characterize food effects on pharmacokinetics. Multiple ascending doses were administered once daily for up to 28 days to assess safety, tolerability, and pharmacokinetic profile following repeated dosing.

Inclusion Criteria:

1. Healthy Male subjects between 18 and 40 years of age (both inclusive).
2. Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests, vital signs and ECG. A subject with a clinically significant abnormality or laboratory parameters significantly outside the reference range for the population being studied may be included only if according to the investigator's opinion, the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures.
3. AST, ALT, alkaline phosphatase and bilirubin ≤1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
4. Non-smoker and non-tobacco user.
5. No history or current practice of alcohol/substance/drug use.
6. No history of psychiatric disorders assessed by a clinical psychological evaluation and DSM V criteria.
7. Body mass index (BMI) between 19 and 27 kg/m2 inclusive.
8. Male subject with female partners of child-bearing potential must agree to use one of the contraception methods. Subjects with female partners of child-bearing potential must use condom while the female partner must use a highly effective contraceptive, such as IUD, birth control pills or diaphragm with spermicide, after the first dose of study treatment and until the end of study visit (for female partners) and during an additional 6 months from the last dose (for subjects themselves).
9. Has a physical condition which enable patients to be fit for a pharmacokinetic sampling according to principal investigator evaluation.
10. Be willing and able to comply with study procedures for the duration of the study.
11. Able to understand and willing to sign written informed consent form.
12. The subjects who are at present, and who can remain drug naïve for at least 14 days prior to dosing and till the end of the study, including herbal supplements, nutraceuticals.
13. Refrain from taking grapefruit, grapefruit juice, orange fruit & orange juice during the study period

Exclusion Criteria:

1. Female volunteers and male volunteers who are either <18 years or >40 years.
2. History of asthma, anaphylaxis or anaphylactoid reactions, severe allergic responses.
3. History of relevant atopy or drug hypersensitivity.
4. Known allergy to any component of RNV-166 oral capsule or its placebo (HPMC or cellulose microcrystalline).
5. History of major medical, psychiatric illness or surgery which, in the judgment of the investigator, puts them 'at risk' or is likely to modify their handling of the study drug.
6. Acute or chronic systemic disease or disorder (respiratory, gastrointestinal, renal, hepatic, hematological, lymphatic, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine).
7. Impaired renal function defined by a creatinine clearance < 90 mL/min calculated using the Cockcroft-Gault equation5 (FDA Guidance for Industry: Pharmacokinetics in patients with Impaired Renal Function, March 2010).
8. History of nephritic colic and/or renal calculi.
9. History of drug abuse and/or regular use of tobacco- or nicotine-containing products >5/day within three months of the study.
10. History of alcohol consumption exceeding, (on average 21 drinks/week for men) within 6 months of the first dose of study medication.
11. Drinking excessive amounts of tea, coffee, chocolate and/or beverage containing caffeine (> 4 cups / day).
12. Vital signs with a clinically significant abnormality at screening.
13. ECG with a clinically significant abnormality at screening.
14. Laboratory test values outside the clinically acceptable 'normal range' for healthy volunteers at screening.
15. Positive HIV, Hepatitis B or Hepatitis C, Tuberculosis, COVID-19 at screening.
16. Positive urine drug test or positive breath alcohol test at screening or at admission to the clinical unit.
17. Any medication (including St John's Wort) within 14 days before administration, or within 5 times the elimination half-life of that drug, whichever is the longest.
18. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to dosing.
19. Unable to refrain from consumption of grapefruit and grapefruit juice, orange fruit & orange juice within 7 days prior to the first dose of study medication.
20. Unwillingness to abstain from sexual intercourse with pregnant or lactating women or to use a condom and spermicide and another form of contraception (e.g., IUD, birth control pills taken by female partner, diaphragm with spermicide) if engaging in sexual intercourse with a woman who could become pregnant until discharge from the study and during 90 additional days.
21. Subjects unlikely to co-operate in the study, and/or poor compliance anticipated by the investigator.
22. Subject being in the exclusion period of a previous trial.
23. Subject who could not be contacted in case of emergency.
24. Subject refusing to give written informed consent.
25. Subject who has received blood or plasma derivatives in the year preceding the study.
26. Subject who has given blood within the past 3 months or have planned to give blood or sperm within the 90 days following the study.
27. Subject who has forfeited their freedom by administrative or legal award, or who is under guardianship or under limited judicial protection.