Drug-Drug Interaction Between THC and AEF0117

Cannabis Abuse Clinical Trial

— DDI  

Official title:

A Double Blind, Placebo-controlled Trial in Healthy Volunteers to Investigate the Effect of Multiple Oral Doses of AEF0117 Versus Placebo on the Pharmacokinetics of THC and Its Metabolites 11 OH THC and THC COOH When Smoking Cannabis.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06395688
• Other study ID #: AEF0117-107
• Secondary ID: U01DA053832
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: June 2024
• Est. completion date: October 2024

Study information

• Verified date: April 2024
• Source: Aelis Farma
• Contact: Meg Haney, PhD
• Phone: +1 646-774-6153
• Email: Meg.Haney[@]nyspi.columbia.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is a single center, double blind, placebo-controlled trial in healthy male and female recreational cannabis users with placebo and AEF0117 dosed in a fixed sequence.

The goal of this clinical trial is to investigate if AEF0117 has any effect on the pharmacokinetics of THC and its metabolites when smoking cannabis.

Description:

The goal of this clinical trial is to investigate if AEF0117 has any effect on the pharmacokinetics of THC and its metabolites when smoking cannabis.

Participants will be male or female in good health aged from 21y to 55y old and who are recreational cannabis users.

The participant will receive either AEF0117 (2 mg) or placebo. The sponsor team, the research staff and the participant won't know which study medication has been given.

The main objectives of the trial are:

• To compare the effect of AEF0117 multiple doses on the maximal plasma concentration and other pharmacokinetic parameters of the THC and its metabolites.

• To investigate safety and tolerability of multiple doses of AEF0117 and when co-administered with a dose of smoked cannabis.

The participant will come for 2 inpatient phases (including one overnight stay). Those 2 inpatient phases are separated by 5 days at home.

After a screening period assessing the good health and the eligibility of the participant, on day 1 they will receive 2 capsules of the study medication and will smoke one cannabis cigarette. During the day, blood samples will be collected at defined timepoints before the study medication, after the study medication and before smoking and after smoking.

On day 2, Blood samples will be collected before and after the study medication intake.

At the end of the assessements, the participant will be discharged. They could be requested to stay at the research facility if they experience any adverse effects From Day 3 to Day 7, the participant will be contacted by phone or by videoconference to confirm the study medication intake and if they experience any adverse events.

On day 8, the participant will come back to the research facility for a 2 days visit including an overnight stay. Assessments and procedures will similar to those performed on Day 1 and Day 2.

On Day 14, the participant will come back to the research facility a last time for a final blood collection.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Healthy males and females of any race, 21 to 55 years old, both inclusive.

2. Subjects must use highly effective contraception.

• Participants who engage in heterosexual sex must use highly effective contraception during the entire trial period. Male participants should refrain from donating sperm or planning a pregnancy throughout the trial. Female participants who are heterosexually active are eligible if: they use highly effective contraception or are post-menopausal and with a negative pregnancy test. Use of hormonal contraception must have been stable for 3 months prior to screening and expected to be unchanged during the trial.

3. Body mass index (BMI) between 20.0 and =35.0 kg/m2 at screening.

4. Be informed of the nature of the trial and provide written informed consent.

5. Be legally competent and able to communicate effectively (in English) with trial personnel.

6. Cannabis smoker (use =1 day the last 2 months and =2 days/week) who agrees to abstain from cannabis (except for what is provided by investigators) for 3 days prior to and including Day 1 and Day 8 of the study, and while in the clinic.

Exclusion Criteria:

1. Severe learning disability, brain damage, or pervasive developmental disorder.

2. Any disease or condition that according to the investigator's medical judgment might compromise the cardiovascular, hematologic, renal, hepatic, pulmonary (including chronic asthma), endocrine (e.g., diabetes), central nervous, or gastrointestinal (including an ulcer) systems.

3. Any clinical laboratory values assessed as clinically significant by the investigator.

4. a) A history of alcohol- or substance use disorders within the past 2 years, recent or current regular use of any illicit drugs except cannabis. In case of a positive drug screen (except for cannabis) at screening, a negative test is required at re-screening.

b) The alcohol breath test and urine drug screen at predose Day 1 must be negative (including for cannabis, a level of THC-COOH <100 ng/mL is allowed).

5. 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), and/or an abnormal Columbia-Suicide Severity Rating Scale (C-SSRS) result (i.e., a C-SSRS score of =3).

6. History of COVID-19 within 4 weeks prior to Day 1, or positive COVID 19 test if required according to standard procedures at the site.

7. A history of difficulty donating blood or inadequate venous access.

8. Blood pressure outside normal range (140/80 mmHg systolic/diastolic) and considered potentially clinically significant by the investigator.

9. A corrected QT interval (Fridericia's correction, QTcF) >450 msec for males and >470 msec for females.

10. Clinically significant anemia or low hemoglobin (levels <9 g/dL) at screening, donation of >250 mL of blood or plasma or received any blood and plasma for medical/surgical reasons within the 30 days prior to receiving trial drug, or intention to donate blood or plasma within 1 month after receiving trial drug.

11. Allergies to the trial drug and known allergies to corn or corn derivatives.

12. Use of any prescription or over-the-counter drug therapy, including psychoactive and/or psychotropic medication, herbal or homeopathic supplements unapproved by the sponsor within 2 weeks prior to receiving the trial drug (for drugs with an elimination half-life greater than 10 days, this will be extended to 60 days).

13. Use of bodybuilding supplements, any food supplement or topical product containing pregnenolone, or any other steroid, including phytosteroids.

14. Use of a diet or supplements (e.g., St. John's Wort), or food and fruit juices (e.g., grapefruit juice, Sevilla oranges) known to induce or inhibit hepatic drug metabolism within 2 weeks prior to receiving the trial drug and until the follow-up visit, unless approved by the sponsor's medical monitor.

15. Tobacco smokers who smoke more than 5 cigarettes per day or use an equivalent daily amount of other tobacco products and are not willing to abstain from tobacco smoking during the inpatient visits.

16. Legal status that would interfere with participation.

17. Unable to follow the restrictions outlined in the protocol.

18. Use of an investigational drug or product, or participation in a drug trial within the last 90 days prior to receiving the trial drug.

19. Participation in a previous trial with AEF0117 within the last 3 months prior to screening.

Related Conditions & MeSH terms

• Cannabis Abuse
• Marijuana Abuse

Intervention

Drug:
• 3ß-(4-methoxybenzyloxy)pregn-5-en-20-one
AEF0117 soft capsules of 1mg
• Placebo
Placebo soft capsules (identical to active compound)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Aelis Farma	National Institute on Drug Abuse (NIDA)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax for co-administration of THC and AEF0117	Comparison of the maximal plasma concentration (Cmax) of THC after co-administration of cannabis cigarette and AEF0117 versus co-administration of cannabis cigarette and placebo.	Day1, Day8
Secondary	AUC for co-administration of THC and AEF0117	Comparison of the area under the curve (AUC) of THC after co-administration of cannabis cigarette and AEF0117 versus co-administration of cannabis cigarette and placebo.	Day1, Day8
Secondary	Tmax for co-administration of THC and AEF0117	Comparison of time of peak concentration of THC after co-administration of cannabis cigarette and AEF0117 versus co-administration of cannabis cigarette and placebo	Day1, Day8
Secondary	Tlag for co-administration of THC and AEF0117	Comparison of Tlag of THC after co-administration of cannabis cigarette and AEF0117 versus co-administration of cannabis cigarette and placebo	Day1, Day8
Secondary	Clast for co-administration of THC and AEF0117	Comparison of Clast of THC after co-administration of cannabis cigarette and AEF0117 versus co-administration of cannabis cigarette and placebo	Day1, Day8
Secondary	t1/2 for co-administration of THC and AEF0117	Comparison of plasma half-life (t1/2) of THC after co-administration of cannabis cigarette and AEF0117 versus co-administration of cannabis cigarette and placebo	Day1, Day8
Secondary	Cmax for 11-OH-THC and THC-COOH	Comparison of peak concentration (Cmax) of 11-OH-THC and THC-COOH after co-administration of cannabis cigarette and AEF0117 versus co-administration of cannabis cigarette and placebo	Day1, Day8
Secondary	AUC for 11-OH-THC and THC-COOH	Comparison of the area under the curve (AUC) of 11-OH-THC and THC-COOH after co-administration of cannabis cigarette and AEF0117 versus co-administration of cannabis cigarette and placebo	Day1, Day8
Secondary	Tmax for 11-OH-THC and THC-COOH	Comparison of the time of peak concentration (Tmax) of 11-OH-THC and THC-COOH after co-administration of cannabis cigarette and AEF0117 versus co-administration of cannabis cigarette and placebo	Day1, Day8
Secondary	Tlag for 11-OH-THC and THC-COOH	Comparison of Tlag of 11-OH-THC and THC-COOH after co-administration of cannabis cigarette and AEF0117 versus co-administration of cannabis cigarette and placebo	Day1, Day8
Secondary	Incidence of TEAEs or TESAEs	Assessed by AE and SAE reporting	From Day1 to Day14
Secondary	Incidence of TEAEs and TESAEs assessed by vital signs	By evaluating changes from the baseline in vital signs	Day1, Day2, Day8, Day9, Day14
Secondary	Effect on heart rate	Measurement of Heart rate over predefined time intervals from prior to IMP dosing until 11 hours after dosing during co-administration of cannabis cigarette and AEF0117 versus co-administration of cannabis cigarette and placebo	Day1, Day8