Randomized, Double-Blind, Placebo-Controlled Phase 1 Study to Evaluate Safety, Tolerability, PK/PD of SAD, MAD and Food Effect of Leucettinib-21 in Healthy Male Subjects, and Single Dose in Subjects With Down Syndrome or Alzheimer's Disease
Leucettinib-21 First-in-Human Phase 1 Study in 4 Parts: Single (Part 1) and Multiple (Part 3) Ascending Doses, and Food-Effect (Part 2) in Healthy Subjects, and Single Dose (Part 4) in People with Down Syndrome (DS) and Alzheimer's Disease (AD). For Parts 1, 3 and 4, safety and tolerability of an oral administration of Leucettinib-21 will be assessed as primary objectives. Pharmacokinetics and pharmacodynamic biomarkers will be investigated as secondary objectives. For Part 2, the effect of high fat meal will be evaluated on the pharmacokinetics parameters after an oral administration of Leucettinib-21.
• Healthy male aged to 18-45 years inclusive;
• Must agree to adhere to the contraception requirements: use of condom by the male subject plus an effective method of contraception for the subject partner of childbearing potential from the time of informed consent signature up to 4 months after last IMP administration. Highly effective method of birth control such as combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intra uterine devices (IUDs), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, true abstinence is acceptable when it is in line with the subject's preferred and usual lifestyle);
• Non-smoker subject or smoker of not more than 5 cigarettes a day;
• Body Mass Index (BMI) between 18.5 and 28,0 (kg/m2) inclusive, with body weight between 60 and 100 kg inclusive, at Screening and Day -1;
• Considered as healthy after a comprehensive clinical assessment (detailed medical history and complete physical examination);
• Normal Blood Pressure (BP), oxygen saturation and Heart Rate (HR) at the screening visit after 10 minutes in supine position:
‣ 95 mmHg ≤ Systolic Blood Pressure (SBP) ≤ 140 mmHg,
⁃ 50 mmHg ≤ Diastolic Blood Pressure (DBP) ≤ 90 mmHg,
⁃ 45 bpm ≤ HR ≤ 90 bpm,
⁃ Or considered NCs by investigators;
• Normal ECG recording on a 12-lead ECG at the screening visit:
‣ 120 ≤ PR \< 210 ms,
⁃ QRS \< 120 ms,
⁃ QTcf ≤ 430 ms for male,
⁃ No sign of any trouble of sinusal automatism,
⁃ Or considered NCs by investigators;
• Laboratory parameters within the normal range of the laboratory (hematology, hemostasis and blood biochemistry tests, urinalysis). Individual values out of the normal range can be accepted if judged clinically non-relevant by the Investigator;
• Normal dietary habits;
⁃ Signing a written informed consent prior to selection;
⁃ Covered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research.