Single Ascending Dose to Study the Safety, Tolerability, PK and PD Effects of AEF0117

NCT03325595 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: AEF0117-101R01DA038875
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (4)

• 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

  168 hours from 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

  168 hours from 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.

  168 hours from 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.

  36 hours from dosing

Secondary Outcomes (10)

• Pharmacokinetics of escalating single oral doses of AEF0117

  144 hours from dosing

• Pharmacokinetics of escalating single oral doses of AEF0117

  144 hours from dosing

• Pharmacokinetics of escalating single oral doses of AEF0117

  144 hours from dosing

• Pharmacokinetics of escalating single oral doses of AEF0117

  144 hours from dosing

• Pharmacokinetics of escalating single oral doses of AEF0117

  144 hours from dosing

Study Arms (2)

Experimental: AEF0117

ACTIVE COMPARATOR

Subjects in Cohorts 1 through 4 receive active treatments. Subjects in Cohorts 1 through 4 will receive a single dose of 0.2, 0.6, 2 and 6mg respectively of AEF0117 on Day1.

Drug: AEF0117

Placebo Comparator: Placebo

PLACEBO COMPARATOR

Subjects in Cohorts 1 through 4 will be randomly assigned in an 6:2 allocation to receive active or placebo treatments.

Drug: Placebo

Interventions

AEF0117 DRUG

0.2, 0.6, 2, or 6mg of AEF0117

Experimental: AEF0117

Placebo DRUG

Matching capsule placebo

Placebo Comparator: Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Be a healthy, non-smoking or smoking (\<10 cigarettes per day) male of any race, at least 18 years old and no more than 55 years old, inclusive. 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 after 90 days, and must report immediately to the study doctor if its partner becomes pregnant during the study and after 90 days. The male subject will have to use double-barrier contraceptive methods: male condoms and spermicide.
• Be a healthy, non-smoking or smoking (\<10 cigarettes per day) female of non-child-bearing potential between 18 years of age and 55 years of age, inclusive. Females may be accepted if they are documented to be surgically sterile (e.g., hysterectomy, tubal ligation) or post-menopausal \[amenorrhea \>1 year and FSH \>25.8mlU/mL, cut off from Labcorp\] with a negative pregnancy test. At least 30% of female.
• Have a body weight ≥50 kg, with a body mass index (BMI) calculated as weight in kg/(height in m)2 from 18 to 30 kg/m2 (inclusive) at screening.
• Have no significant diseases in the medical history and no clinically significant findings on physical examination including ECG, BP, HR, RR, temperature, C-SSRS test. Routine laboratory values should be within normal ranges or considered as NCS by the investigator. The Non Clinical Significant nature of the deviation will result from the integration of a full clinical examination with physical examination and lab tests in that contest by a certified physician.
• Be informed of the nature of the study and provide written informed consent.
• Be legally competent and able to communicate effectively with study personnel.

You may not qualify if:

• Allergies to the Investigational Medicinal Product (IMP) or placebo and its excipients and known allergies to pregnenolone or its matching placebo or its ingredient
• Acute signs of intoxication at screening or baseline assessment due to opiates or any type of stimulants, causing cognitive impairments
• Severe learning disability, brain damage or pervasive developmental disorder ( as this may affect one of the end point that is being targeted)
• Any disease or condition that might compromise the cardiovascular, hematological, renal, hepatic, pulmonary (including chronic asthma), endocrine (e.g., diabetes), central nervous, or gastrointestinal (including an ulcer) systems.
• Have abnormal baseline values for the steroid hormones: cortisol, testosterone, estradiol and progesterone in accordance to their reproductive status (for example but not limited to surgical sterile or post-menopausal).
• A history of alcoholism or drug addiction within the past 2 years, recent use (in the last month) of any recreational drugs, or positive results from a urine screen for substances of abuse or from an alcohol breath test.
• A history of or current serious mental illness including active or recent suicidal ideation, severe psychological distress (e.g., active suicidal plans, psychosis, debilitating panic disorder) or/and an abnormal C-SSRS result.
• A history of difficulty donating blood or inadequate venous access.
• The donation of blood or plasma within 30 days prior to receiving study medication or received any blood and plasma for medical/surgical reasons or intention to donate blood or plasma within one month after receiving the study drug.
• A positive hepatitis screen that tests for both hepatitis B surface antigen (HBsAg) and antibody to hepatitis C (HCV).
• A positive test result for HIV antibody by enzyme immunoassay which is confirmed by Western immunoblot.
• Ingestion of an investigational drug or product, or participation in a drug study within a period of 30 days prior to receiving study medication (for investigational drugs with an elimination half-life greater than 10 days, this will be extended to 60 days).
• Use of any prescription or over-the-counter (OTC) drug therapy, including herbal, homeopathic, vitamins, minerals and nutritional supplements, bodybuilding supplements unapproved by the sponsor, within 2 weeks prior to receiving the study medication (for drugs with an elimination half-life greater than 10 days, this will be extended to 60 days). The use of any food supplement or body cream containing pregnenolone or any other steroid including phytosteroids.
• Use of a drug therapy known to induce or inhibit hepatic drug metabolism within 30 days prior to receiving study medication or during the study.
• Use of psychoactive and/or psychotropic medication (including sedative, antidepressant and antipsychotics), or medication that alters the hypothalamic pituitary adrenal (HPA) Axis functioning and any medications that alter heart rate or skin conductance monitoring.

Sponsors & Collaborators

• Aelis Farma: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Biotrial Inc

Newark, New Jersey, 07103, United States

Location

Related Publications (1)

• Haney M, Vallee M, Fabre S, Collins Reed S, Zanese M, Campistron G, Arout CA, Foltin RW, Cooper ZD, Kearney-Ramos T, Metna M, Justinova Z, Schindler C, Hebert-Chatelain E, Bellocchio L, Cathala A, Bari A, Serrat R, Finlay DB, Caraci F, Redon B, Martin-Garcia E, Busquets-Garcia A, Matias I, Levin FR, Felpin FX, Simon N, Cota D, Spampinato U, Maldonado R, Shaham Y, Glass M, Thomsen LL, Mengel H, Marsicano G, Monlezun S, Revest JM, Piazza PV. Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials. Nat Med. 2023 Jun;29(6):1487-1499. doi: 10.1038/s41591-023-02381-w. Epub 2023 Jun 8.

  PMID: 37291212 DERIVED

Study Officials

• Michael Dobrow, MD

  Biotrial Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: This will be a double-blind study. Subjects and investigator will be masked.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2017
• First Posted: October 30, 2017
• Study Start: April 6, 2017
• Primary Completion: February 26, 2018
• Study Completion: February 26, 2018
• Last Updated: March 13, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)