Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of CB1 Antagonist ANEB-001 in a THC Challenge Model

• ClinicalTrials.gov Identifier: NCT05282797
• Recruitment Status: Active, not recruiting
• First Posted: March 16, 2022
• Last Update Posted: February 2, 2023
• Sponsor: Anebulo Pharmaceuticals
• Information provided by (Responsible Party): Anebulo Pharmaceuticals

Study Description

Brief Summary:

The aim of this study is to investigate whether ANEB-001 effectively penetrates the brain and inhibits the psychotropic effects of Δ9-Tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis. This randomized, placebo-controlled, double-blind study is designed as a proof-of-pharmacology and dose finding study for the antagonistic effect of ANEB-001 during a THC challenge. Results of this study will inform the future potential use of ANEB-001 as an emergency treatment for THC intoxication.

Condition or disease	Intervention/treatment	Phase
Acute Cannabinoid Intoxication	Drug: ANEB-001; Drug: Placebo	Phase 2

Detailed Description:

A randomized study is planned over a 12 month period to evaluate whether ANEB-001 effectively penetrates the brain and inhibits the psychotropic effects of Δ9-Tetrahydrocannabinol (THC). All cohorts will be randomized, double-blind and placebo-controlled. Randomization is deemed appropriate to avoid selection bias for active compound or placebo treatment. A double-blind and placebo-controlled design is deemed appropriate because of the safety, tolerability and pharmacodynamic assessments that will be performed in this study. By double-blinding the study, bias arising from study subject's or investigator's knowledge about treatment assignment is avoided. The investigator, sponsor team, all site staff and all related parties with direct involvement in study conduct will remain fully blinded throughout the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 134 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Oral Doses of CB1 Antagonist ANEB-001 in Healthy Occasional Cannabis Users
• Actual Study Start Date: December 15, 2021
• Estimated Primary Completion Date: June 30, 2023
• Estimated Study Completion Date: June 30, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part A - 100 mg of ANEB-001; Subjects receive 21 mg of THC and 100 mg of ANEB-001	Drug: ANEB-001; Experimental Treatment
Experimental: Part A - 50 mg of ANEB-001; Subjects receive 21 mg of THC and 50 mg of ANEB-001	Drug: ANEB-001; Experimental Treatment
Placebo Comparator: Part A - Placebo; Subjects receive 21 mg of THC and a placebo	Drug: Placebo; Placebo comparator
Experimental: Part B - Cohort 1 - ANEB-001; Subjects receive 21 mg of THC and 30 mg of ANEB-001	Drug: ANEB-001; Experimental Treatment
Placebo Comparator: Part B - Cohort 1 - Placebo; Subjects receive 21 mg of THC and a placebo	Drug: Placebo; Placebo comparator
Experimental: Part B - Cohort 2 - ANEB-001; Subjects receive 21 mg of THC and 10 mg of ANEB-001	Drug: ANEB-001; Experimental Treatment
Placebo Comparator: Part B - Cohort 2 - Placebo; Subjects receive 21 mg of THC and a placebo	Drug: Placebo; Placebo comparator
Experimental: Part B - Cohort 3 - ANEB-001; Subjects receive 21 mg of THC and 1 hour later, 30 mg of ANEB-001	Drug: ANEB-001; Experimental Treatment
Placebo Comparator: Part B - Cohort 3 - Placebo; Subjects receive21 mg of THC and 1 hour later, placebo	Drug: Placebo; Placebo comparator
Experimental: Part B - Cohort 4 - ANEB-001; Subjects receive a dose of THC (to be determined) and a dose of ANEB-001 (to be determined)	Drug: ANEB-001; Experimental Treatment
Placebo Comparator: Part B - Cohort 4 - Placebo; Subjects receive a dose of THC (to be determined) and a placebo	Drug: Placebo; Placebo comparator
Experimental: Part B - Cohort 5 - ANEB-001; Subjects receive a dose of THC (to be determined) and a dose of ANEB-001 (to be determined)	Drug: ANEB-001; Experimental Treatment
Placebo Comparator: Part B - Cohort 5 - Placebo; Subjects receive a dose of THC (to be determined) and a placebo	Drug: Placebo; Placebo comparator
Experimental: Part B - Cohort 6 - ANEB-001; Subjects receive a dose of THC (to be determined) and a dose of ANEB-001 (to be determined)	Drug: ANEB-001; Experimental Treatment
Placebo Comparator: Part B - Cohort 6 - Placebo; Subjects receive a dose of THC (to be determined) and a placebo	Drug: Placebo; Placebo comparator

Outcome Measures

Primary Outcome Measures :

1. Sensation of Feeling High [ Time Frame: Day 1 ]
   Feeling High on a visual analog scale (mm)
2. Body sway [ Time Frame: Day 1 ]
   antero-posterior sway (mm);
3. Sensation of Alertness [ Time Frame: Day 1 ]
   Alertness on a visual analog scale (mm)
4. Heart Rate [ Time Frame: Day 1 ]
   Heart Rate in beats/min

Secondary Outcome Measures :

1. Sensation of Mood [ Time Frame: Day 1 ]
   Mood on a visual analog scale (mm)
2. Sensation of Calmness [ Time Frame: Day 1 ]
   Calmness on a visual analog scale (mm)
3. Feeling of Drug Effect [ Time Frame: Day 1 ]
   Feeling of drug effect on a visual analog scale (mm)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Signed informed consent prior to any study-mandated procedure
• BMI between 18 and 30 kg/m2
• Minimum weight 50 kg
• Occasional cannabis user

Exclusion Criteria:

• Evidence of active or chronic condition that could interfere with, or which the treatment of might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in the opinion of the investigator
• Clinically significant abnormalities, as judged by the investigator
• Positive Hepatitis B surface antigen, Hepatitis C antibody or HIV antibody at screening
• Systolic blood pressure greater than 130 or less than 90 mm Hg and diastolic blood pressure greater than 95 or less than 50 mm Hg at screening Abnormal findings in the resting electrocardiogram
• Use of any medications within 7 days of study drug administration, or less than 5 half-lives (whichever is longer). Exceptions are paracetamol and ibuprofen and topical medications.
• Use of any vitamin, mineral, herbal and dietary supplements within 7 days of study drug administration, or less than 5 half-lives (whichever is longer)
• Participation in an investigational drug or device study (last dosing of previous study was within 90 days prior to first dosing of this study)
• History of abuse of addictive substances (alcohol, illegal substances) or current use of more than 21 units alcohol per week, drug abuse, or regular user of sedatives, hypnotics, tranquilizers, or any other addictive agent other than recreative use of THC
• Positive test for drugs of abuse (other than THC) at screening.
• Positive test for drugs of abuse pre-dose
• Clinically significant suicidal ideation in the past 5 years as judged by the investigator or any life-time suicide attempts
• History of cannabis-induced psychosis, schizophrenia or other clinically relevant psychiatric disorders, as judged by the investigator.
• History of a clinically significant mood disorder, including but not limited to major depressive disorder, as judged by the investigator.

Contacts and Locations

Locations

Netherlands

Centre for Human Drug Research (CHDR)

Leiden, ZH, Netherlands, 2333

Sponsors and Collaborators

Anebulo Pharmaceuticals

Investigators

• Principal Investigator: GJ Groeneveld, MD, PhD; CHDR

More Information

• Responsible Party: Anebulo Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05282797
• Other Study ID Numbers: AN01AC11
• First Posted: March 16, 2022
• Last Update Posted: February 2, 2023
• Last Verified: January 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No