Efficacy of PP-01 in Mitigating Cannabis Withdrawal Symptoms in Adults With Cannabis Use Disorder

PleoPharma

Status and phase: Enrolling; Phase 3

Conditions: Cannabis Withdrawal

Treatments: Combination Product: PP-01; Drug: Nabilone; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07644052

CAN-004

Details and patient eligibility

About

This study is a randomized, double-blind, placebo and active-controlled, multicenter trial conducted to evaluate whether PP-01 mitigates the withdrawal symptoms associated with discontinuing cannabis in participants with moderate to severe cannabis use disorder (CUD). Study participants will receive PP-01, nabilone, or placebo every day for 34 days. The total study duration will be approximately 78 days, including screening and a one-week inpatient stay. Following the initial inpatient portion of the study, participants will return to the clinic for six clinic visits and complete two telemedicine appointments. Participants will complete daily symptom diaries and other study-related questionnaires.

Participants who complete the core study may be eligible to participate in a repeat dosing extension study if they meet required criteria.

Enrollment: 420 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Generally healthy adults between the ages of 18 and 55, inclusive.
2. Meet DSM-5 diagnostic criteria for current moderate to severe CUD as confirmed by a licensed physician or psychologist or addiction medicine specialist.
3. BMI within 18.0 to 38.0 kg/m2, inclusive.
4. Female participants must not be pregnant or lactating. If of childbearing potential - the participant agrees to use an accepted contraceptive regimen.
5. Male participants who are fertile and engage in sexual activity must agree to use a double barrier method (e.g., condom and spermicide) during the study and to not donate sperm for 90 days after the last dose of study medication.
6. Be seeking and motivated to discontinue cannabis and to minimize withdrawal symptoms.
7. Agree to not use cannabis or any product containing CBD, hemp derivatives, terpenes or any THC containing product including delta-8, delta-10, THC-A or any other cannabinoid-like product following Randomization and throughout the study duration.
8. Meet DSM-5 Cannabis Withdrawal Criteria.
9. Report heavy use of daily/near daily cannabis.
10. Have a urine drug screen positive for THC/THC metabolite and have a negative result for all other illicit/excluded drugs and alcohol at Screening and Randomization.
11. Capable of giving informed consent and stated willingness to comply with all study procedures including inpatient and weekly outpatient visits, daily evening video calls, restrictions, and availability for the duration of the study.
12. Willing to be admitted to an inpatient clinic with overnight stays on Days 1 through 6 and return for all outpatient visits.
13. Ability to take study drug capsules at approximately the same time each day.
14. Have regular access to the internet and access to video/virtual capabilities for video calls by any means.
15. Agree to not use any alcohol during the study.
16. No plan to change current nicotine use.
17. Ability to read, understand, and complete daily diaries.

Exclusion criteria

1. Lifetime history of DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder.

2. Current DSM-5 criteria for a psychiatric disorder that in the Investigator's judgment is unstable, would be disrupted by the study medication, or is likely to require new pharmacotherapy or psychotherapy during the study period. Individuals who are currently stable on psychotropic medication for at least 3 months may be included at the discretion of the Investigator's judgement.

3. Participants who meet DSM-5 criteria for any history of or current drug use disorder within the previous 2 years, other than cannabis, nicotine, or caffeine use disorders.

4. Participants who consume alcohol on a regular or frequent basis and who do not agree or are deemed by the Investigator to be unable to discontinue alcohol for the duration of the study.

5. Participants using cannabis for a physician directed medical condition requiring use such as epilepsy.

6. Any clinically important abnormalities on Screening physical examination, assessments, electrocardiogram, or laboratory tests.

7. Current or recent history of significant violent or suicidal behavior, risk for suicide or homicide.

8. History of clinically significant medical condition that, in the opinion of the Principal Investigator, would jeopardize the safety of the participant or impact on the validity of the study results.

9. Participants with risk factors for seizure.

10. Known history of allergy, intolerance, or hypersensitivity to nabilone, gabapentin, or pregabalin.

11. Prohibited medications at Screening:

    • Current use of narcotics, psychedelics, stimulants, opioid agonists and antagonists, kratom, illicit drugs, ketamine, unregulated psychoactive drugs (sometimes known as "gas station drugs"), or products intended to induce a feeling of being high except for cannabis
    • Regular benzodiazepine use (more than once per week) and no use within 7 days of Baseline Visit (Day 1)
    • Current use (within 7 days of Baseline Visit) of OTC products to help with sleep or anxiety
    • Prescription medications to help with sleep or anxiety within 14 days of Screening
    • Current use of nabilone, dronabinol, Sativex, Epidiolex, synthetic cannabinoids
    • Gabapentin or pregabalin or use within 30 days of Screening

12. Heavy users of alcohol within 60 days of Screening or binge drinkers of alcohol within 30 days of Screening.

13. A positive urine drug/alcohol test at Screening or Randomization for narcotics and/or illicit drugs other than cannabis. If the test is positive for benzodiazepines or alcohol at Screening, and if it is reported that they are only occasional users, a repeat urine drug screen can be performed at the discretion of the Medical Monitor and must be negative at the time of Randomization.

14. Use of an investigational drug or biologic within 30 days or 5 times the half-life (whichever is longer) prior to the Screening Visit.

15. Active influenza or COVID-19 infection or planned vaccination.

16. Prior participation in any PleoPharma clinical study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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420 participants in 3 patient groups, including a placebo group

PP-01

Experimental group

Description:

Oral PP-01 tapered/titrated over 34 days

Treatment:

Combination Product: PP-01

Nabilone

Active Comparator group

Description:

Oral Nabilone tapered/titrated over 34 days

Treatment:

Drug: Nabilone

Placebo

Placebo Comparator group

Description:

Oral Placebo given daily for 34 days

Treatment:

Drug: Placebo