AEF0217 First-in-Human Phase I Study in 3 Parts (Single and Multiple Ascending Doses, and Food Effect) in Healthy Subjects.

A First-In-Human Phase I Study in 3 Parts: Randomized, Double-blind, Placebocontrolled, Sequential Group Investigation of the Safety, Tolerability, Pharmacokinetics of AEF0217 After Oral, Single and Multiple Ascending Doses, and an Open Label, Cross-over Investigation of the Effect of Food on the Bioavailability of AEF0217 in Healthy Volunteers.

This trial is divided in 3 parts: FIH-SAD (Single Ascending Doses), FIH-MAD (Multiple Ascending Doses) and FIH-FE (Food effects). FIH-SAD will start first. The start of FIH-MAD will await the results of at least three cohorts from the FIHSAD study before initiated. The starting dose of the FIH-MAD will have been shown to be well tolerated and one dose level lower than the highest dose for which safety, tolerability and pharmacokinetic (PK) data are available. FIH-FE will be the last to start after the completion of FIH-SAD and conducted in parallel with parts of FIH-MAD.

Inclusion Criteria:

• Healthy male subjects: As the effect of the study drug on sperm is still unknown, male subjects should refrain from donating sperm or plan a pregnancy with their partner throughout the study and until 90 days after the trial and must report immediately to the study doctor if its partner becomes pregnant during the trial and during 90 days after the trial. The male subject will have to use double-barrier contraceptive methods: male condoms and spermicide.
• Healthy female subjects of non-child-bearing potential: females may be accepted if they are documented to be surgically sterile i.e., hysterectomy, tubal ligation or post-menopausal with a negative pregnancy test (Not applicable for FIH-FE part III as it includes male only)
• Age ≥ 18 and ≤ 55 years.
• Weight ≥ 50 kg and ≤ 100 kg.
• Body mass index (BMI) ≥ 18 and ≤ 30.
• Negative serum pregnancy test (women only)
• Non-smoking.
• No history of or ongoing clinically relevant diseases or conditions.
• No clinically relevant findings in physical examination, vital signs (blood pressure, heart rate and body temperature), ECG and safety laboratory parameters that should be within normal ranges or considered as non-clinically relevant by the investigator.
• Negative covid19 PCR test within 72h before admission
• Able/willing to accept restrictions regarding diet, physical exercise, and consumption of alcohol and/or xanthine containing items when out of CRU.
• Able to read Spanish and adhere to study requirements.
• Not under any administrative or legal supervision.
• Signed informed consent prior to any study-mandated procedure.

Exclusion Criteria:

• Women of child-bearing potential
• Life-time substance use disorders (SUD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).
• Recreational use of drugs of abuse within the last month prior to study drug administration.
• Positive blood or urine test for drugs of abuse or alcohol breath test prior to study drug administration.
• Life-time history of bipolar disorders, psychosis or suicidal attempts assessed by the Dual Diagnosis Screening Instrument (DDSI).
• History of anxiety or depression not completely recovered within 12 months prior to study drug administration, as assessed by the DDSI.
• Lifetime history of deliberate self-harm due to suicidal ideation or suicidal ideation prior to study drug administration, as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS).
• Clinically relevant cognitive impairment preventing the administration of the psychometric tests
• Any other clinically relevant disease or condition that in the judgment of the investigator might interfere with the subject's ability to comply with study procedures or requirements and/or bias the interpretation of the study results and/or jeopardize the subject's safety.
• Ongoing gastrointestinal diseases or history of gastrointestinal surgery affecting absorption
• Subjects with a clinically significant disease within one month prior to study drug administration.
• Any clinically relevant findings in physical examination, vital signs, ECG and safety laboratory parameters.
• Positive hepatitis or HIV test.
• Positive Covid19 PCR test within 72h before admission (Day -1) to the research facility
• Have abnormal screening values for the steroid hormones: cortisol, testosterone, estradiol and progesterone relative to their reproductive status.
• Known hypersensitivity to any drug (in particular steroids) or drug excipients.
• Use of drugs known to induce or inhibit hepatic drug metabolism within one month prior to study administration or during the study and use of citrus juice during the study.
• Any prescription or over-the-counter (OTC) product including herbal, homeopathic, vitamins, minerals and nutritional supplements and in particular any parenteral or topical product containing steroids, within 2 weeks (or more considering the elimination half-life of the product) prior to study drug administration
• Donation of blood or plasma within one month prior to study drug administration or transfusion of blood or plasma for medical/surgical reasons or intention to donate blood or plasma within one month after study drug administration.
• History of inadequate venous access and/or experience of difficulty donating blood.
• Not able/not willing to accept restrictions regarding diet, physical exercise, and consumption of alcohol and/or xanthine containing items when out of CRU.
• Subject included in a clinical study within 3 months prior to study drug administration.
• Subject already included in other parts of this study