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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
24
0.6, 2 and 6mg of AEF0117
Matching placebo capsule
Biotrial Inc
Newark, New Jersey, United States
Incidence of treatment-emergent AEs and SAEs as assessed by vital signs
Evaluation by grade intensity and by evaluating changes from the baseline in vital signs
Time frame: since the first administration until 264 hours from last dosing
Incidence of treatment-emergent AEs and SAEs as assessed by ECGs
Evaluation by grade intensity and by evaluating changes from the baseline in ECGs
Time frame: since the first administration until 264 hours from last dosing
Incidence of treatment-emergent AEs and SAEs as assessed by clinical laboratory values
Evaluation by grade intensity and by evaluating changes from the baseline in clinical laboratory values from blood and urine samples.
Time frame: since 24 hours from the first administration until 264 hours from last dosing
Incidence of treatment-emergent AEs and SAEs as assessed by psychometric tests
Evaluation by grade intensity and by evaluating changes from the baseline in psychometric tests (Bond and Lader VAS, ARCI, POMS) and C-SSRS test.
Time frame: 24 hours from dosing
Pharmacokinetics of escalating multiple oral doses of AEF0117
Peak Plasma Concentration (Cmax) induced by multiple doses of AEF0117 will be determined based on serial blood sample collections and plasma AEF0117 concentration.
Time frame: 264 hours from last dosing
Pharmacokinetics of escalating multiple oral doses of AEF0117
Lowest Peak Plasma (Cmin) induced by multiple doses of AEF0117 will be determined based on serial blood sample collections and plasma AEF0117 concentration.
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Time frame: 264 hours from last dosing
Pharmacokinetics of escalating multiple oral doses of AEF0117
Time to maximum plasma concentration (tmax) of multiple doses of AEF0117 will be determined based on serial blood sample collections and plasma AEF0117 concentration.
Time frame: 264 hours from last dosing
Pharmacokinetics of escalating multiple oral doses of AEF0117
Terminal elimination half-life (t1/2) based on serial blood sample collections and plasma AEF0117 concentration.
Time frame: 264 hours from last dosing
Pharmacokinetics of escalating multiple oral doses of AEF0117
Time to last measurable plasma concentration (tlast) based on serial blood sample collections and plasma AEF0117 concentration.
Time frame: 264 hours from last dosing
Pharmacokinetics of escalating multiple oral doses of AEF0117
Area under the plasma concentration versus time curve from time 0 (AUC0-t) based on serial blood sample collections and plasma AEF0117 concentration.
Time frame: 264 hours from last dosing
Pharmacodynamics of escalating multiple oral doses of AEF0117
Peak Plasma Concentration (Cmax) induced by multiple doses of AEF0117 on plasma pregnenolone, DHEA, allopregnanolone, testosterone and endocannabinoids (AEA and 2AG) and serum estradiol, progesterone and cortisol concentrations.
Time frame: 120 hours from last dosing
Pharmacodynamics of escalating multiple oral doses of AEF0117
Lowest Peak Plasma (Cmin) induced by multiple doses of AEF0117 on plasma pregnenolone, DHEA, allopregnanolone, testosterone and endocannabinoids (AEA and 2AG) and serum estradiol, progesterone and cortisol concentrations.
Time frame: 120 hours from last dosing
Pharmacodynamics of escalating multiple oral doses of AEF0117
Time to maximum plasma concentration (tmax) of multiple doses of AEF0117 on plasma pregnenolone, DHEA, allopregnanolone, testosterone and endocannabinoids (AEA and 2AG) and serum estradiol, progesterone and cortisol concentrations.
Time frame: 120 hours from last dosing
Pharmacodynamics of escalating multiple oral doses of AEF0117
Area under the plasma concentration versus time curve from time 0 (AUC0-t) of multiple doses of AEF0117 on plasma pregnenolone, DHEA, allopregnanolone, testosterone and endocannabinoids (AEA and 2AG) and serum estradiol, progesterone and cortisol concentrations.
Time frame: 120 hours from last dosing