Multiple Ascending Dose to Study the Safety, Tolerability, PK and PD Effects of AEF0117
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      The study is designated to evaluate the safety, tolerability, pharmacokinetics (PK) and
      pharmacodynamics (PD) of escalating multiple oral doses of AEF0117 in healthy adult male and
      female subjects.
    

Detailed description: 
      The overall goal of this protocol is to evaluate the safety, tolerability, pharmacokinetics
      (PK) and pharmacodynamics (PD) of escalating multiple oral doses of AEF0117. This will be a
      single center study in healthy male and female subjects. The study design will be a
      double-blind, randomized, placebo-controlled, single period, parallel group, multiple dose
      escalation with AEF0117.

      Three dose levels are planned for the study with 8 subjects (6 active and 2 placebo) per dose
      level:

      Dose Level I - 0.6 mg multiple oral dose of AEF0117 given on the morning of Day 1 to Day 7
      Dose Level II - 2 mg multiple oral dose of AEF0117 given on the morning of Day 1 to Day 7
      Dose Level III - 6 mg multiple oral dose of AEF0117 given on the morning of Day 1 to Day 7

      The planned dose escalation schema may be amended based on the emerging PK and safety data,
      and an additional cohort may be added. Smaller dose escalation increments can also be
      implemented based on safety and PK results of previous dose levels. Each subject will
      participate in only one dose group.

      Administration of AEF0117 to each dose cohort should not occur before participants in the
      previous dose cohort have been treated and data i.e. safety results and PK from those
      participants are reviewed in accordance with the protocol. Eligible subjects will be admitted
      to the research clinic at midday prior to dosing (Day -1) and remain in house until Day 14.
      Subsequently subjects will return to the research facility on an outpatient basis to have PK
      and safety assessments at 216 and 264 hours (Day 16 and Day 18) after the last dose (Day 7).
      PK samples and safety assessments will be done pre-dose and at different times post-dose.

      Randomized subjects will receive a single oral dose per day on Days 1 through 7. Serial PK
      and PD blood samples and urine PK collections will be performed for 24 hours after the first
      dose administration (Day 1). Pre-dose PK and PD blood samples will then be obtained on Days
      3, 4, 5 and 6 prior to the daily dose administration. Serial PK and PD blood samples and
      urine collections will be also performed for 48 hours after the last dose (Day 7), and blood
      samples will be obtained at 72, 96, 120, 144, 168, 216 and 264 hours after the last dose (Day
      7).

      Safety monitoring (physical examinations, vital sign measurement, 12 lead ECGs, clinical
      safety laboratory tests, and adverse event monitoring) will be performed throughout the
      study. Psychometrics tests (Bond & Lader VAS, ARCI, POMS) will be performed on D1 and D7 at
      pre-dose, tmax and 24 hours post-dose. CSSRS test will be performed at pre-dose of D1 and at
      D8. tmax will be determine according to PK results obtained in the AEF0117-101 clinical
      study. Subjects will have a final follow up/Study termination safety evaluation on Day 18.
    

Intervention name(s): AEF0117 oral capsule; Placebo oral capsule
Intervention type(s): Drug; Drug
Intervention description(s): 0.6, 2 and 6mg of AEF0117; Matching placebo capsule
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment