A Combined SAD and MAD Study to Investigate the Safety, Tolerability and Pharmacokinetic Profile of IFB-088
Condition: Healthy Volunteers
Intervention: IFB-088 (2.5-60.0mg) oral capsule; Placebo (2.5-60.mg) oral capsule; IFB-088 (15.0-50.0mg) oral capsule; Placebo oral (15.0-50.0mg) capsule
Intervention description: SAD phase: IFB-088 will be administered during 1 day, in one (2.5mg) or 2 (5.0-60.0mg) intakes separated by an interval of 12 hours; SAD phase: placebo (microcrystalline cellulosis) will be administered during 1 day, in one (2.5mg) or 2 (5.0-60.0mg) intakes separated by an interval of 12 hours; MAD phase: multiple doses of IFB-088 (15.0-50.0mg) will be administered daily during 14 days, in two intakes, separated by an interval of 12 hours.; MAD phase: multiple doses of placebo (microcrystalline cellulosis, 15.0-50.0mg) will be administered daily during 14 days, in two intakes, separated by an interval of 12 hours.
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: double-blind, randomized, placebo-controlled, combined single and multiple ascending dose of IFB-088 by successive cohorts study
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: Capsules used for verum or placebo (Size 5 white opaque HPMC capsule) are identical and equally-weighted
Enrollment: 72.0
Sex: Male
Minimum age: 18 Years
Maximum age: 40 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: First-In-Human

Summary:

      This is the first study of single and multiple doses of IFB-088 in human subjects. The
      current study is designed to assess in the first part, the safety, tolerability, plasma and
      urine pharmacokinetics (PK) of single oral doses of IFB-088 in healthy subjects (Single
      Ascending Doses - SAD) and in a second part safety, tolerability, plasma and urine
      pharmacokinetics (PK) of multiple oral doses of IFB-088 in healthy subjects (Multiple
      Ascending Doses - MAD)
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy male 18 to 40 years of age inclusive, Caucasian.

          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.

          3. AST, ALT, alkaline phosphatase and bilirubin < or = 1.5xULN (isolated bilirubin
             >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).

          4. ECG (12 leads) normal (120<PR<200ms; QRS<120ms; QTcF<450ms) and/or without clinically
             relevant impairments as judged by investigator.

          5. Non-smoker, or user of not more than tobacco- or nicotine-containing products ≤ 5
             cigarettes a day.

          6. Negative screen for alcohol and drugs of abuse at screening and admission.

          7. No history of psychiatric disorders assessed by a clinical psychological evaluation
             and the Mini International Neuropsychiatric Interview (MINI).

          8. Body mass index (BMI) between 19 and 27 kg/m² inclusive.

          9. Subject with female partners of child bearing potential must agree to use one of the
             contraception methods listed in Section 6.6.1 (Contraception requirements). This
             criterion must be followed from the time of the first dose of study medication until
             the follow up visit (for female partners) and with an additional period of 90 days
             (for subjects themselves).

         10. Willing and able to understand and sign an approved Informed Consent Form.

         11. Able to understand the protocol and to come to the visits.

         12. Who is, in the judgement of the investigator likely to be compliant during the study.

         13. Subject registered in the VRB file (volontaires se prêtant à des recherches impliquant
             la personne humaine).

         14. Covered by Health Insurance System and / or in compliance with the recommendations of
             National Law in force relating to biomedical research.

        Exclusion Criteria:

          1. 1. History of asthma, anaphylaxis or anaphylactoid reactions, severe allergic
             responses.

          2. History of relevant atopy or drug hypersensitivity.

          3. Known allergy to any component of IFB-088 oral capsule or its placebo (HPMC or
             cellulose microcrystalline).

          4. 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.

          5. Acute or chronic systemic disease or disorder (respiratory, gastrointestinal, renal,
             hepatic, haematological, lymphatic, neurological, cardiovascular, psychiatric,
             musculoskeletal, genitourinary, immunological, dermatological, endocrine).

          6. Impaired renal function defined by a creatinine clearance < 90 mL/min calculated using
             the Cockcroft-Gault equation (according the FDA Guidance for Industry:
             Pharmacokinetics in patients with Impaired Renal Function, March 2010).

          7. History of nephritic colic and/or renal calculi.

          8. History of drug abuse and/or regular use of tobacco- or nicotine-containing products >
             5/day within three months of the study.

          9. History of alcohol consumption exceeding, (on average 21 drinks/week for men) within 6
             months of the first dose of study medication.

         10. Drinking excessive amounts of tea, coffee, chocolate and/or beverage containing
             caffeine (> 4 cups / day).

         11. Vital signs with a clinically significant abnormality at screening.

         12. ECG with a clinically significant abnormality at screening.

         13. Laboratory test values outside the clinically acceptable 'normal range' for healthy
             volunteers at screening.

         14. Positive HIV, Hepatitis B or Hepatitis C at screening.

         15. Positive urine drug test or positive breath alcohol test at screening or at admission
             to the clinical unit.

         16. 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
             (except paracetamol).

         17. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is
             longer) prior to screening.

         18. Unable to refrain from consumption of grapefruit or grapefruit juice within 7 days
             prior to the first dose of study medication.

         19. 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.

         20. Subjects unlikely to co-operate in the study, and/or poor compliance anticipated by
             the investigator.

         21. Subject being in the exclusion period of a previous trial.

         22. Subject having exceeded the earnings for the last 12 months, including the indemnities
             for the present study.

         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 has 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.