Effect of PP-01 on Cannabis Withdrawal Syndrome

Study Overview
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Brief Summary
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This study will be a randomized, double-blind, placebo-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). The study will enroll approximately 225 participants with moderate to severe CUD and will include 5 arms, including a placebo arm, to help assess the incidence and severity of withdrawal symptoms in heavy long-term users of cannabis. Participants receive study medication for 34 days and participate in 11 visits (7 at a clinic and 4 telemedicine).

Official Title
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A Phase 2, Multicenter, Randomized, Double-Blind, Multiple-Dose, Placebo Controlled Clinical Trial of Two Doses of PP-01 for the Mitigation of Cannabis Withdrawal Symptoms

Conditions
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Cannabis Withdrawal

Intervention / Treatment
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* Combination Product: PP-01 High Dose
* Combination Product: PP-01 Low Dose
* Drug: Placebo
* Drug: Nabilone
* Drug: Gabapentin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Generally healthy individuals between the ages of 18 and 55, inclusive Meets Diagnostic and Statistical Manual (DSM)-5 diagnostic criteria for current moderate to severe CUD as confirmed by a licensed physician or psychologist or addiction medicine specialist BMI within 18.0 to 38.0 kg/m2, inclusive Seeking to minimize withdrawal symptoms related to cannabis discontinuation in people seeking to discontinue cannabis Meet DSM-5 Cannabis Withdrawal Report heavy use of daily/near daily cannabis Have a urine drug screen positive for tetrahydrocannabinol (THC)/THC metabolites at Screening and Randomization Capable of giving informed consent and complying with study procedures Stated willingness to comply with all study procedures including twice weekly visits, daily evening video calls, restrictions, and availability for the duration of the study Exclusion Criteria: Lifetime history of DSM-5 diagnosis of schizophrenia or schizoaffective disorder, or Bipolar 1 within the previous 2 years 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 Participants who meet DSM-5 criteria for any substance use disorder other than cannabis, nicotine, or caffeine use disorders Participants using cannabis for a medical condition requiring use such as epilepsy Clinically significant unstable medical disorders Any clinically important abnormalities on Screening physical examination (PE), assessments, ECG, or laboratory tests Use of an investigational drug or biologic within 30 days or 5 times the half-life (whichever is longer) prior to the Screening Visit Pregnant or lactating female participants, or a positive urine pregnancy test COVID-19

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PP-01 High Dose<br>Oral PP-01 High Dose tapered/titrated over 34 days | Combination Product: PP-01 High Dose<br>* Cannabinoid-1 (CB1) partial agonist / GABAergic modulator<br>|
| Experimental: PP-01 Low Dose<br>Oral PP-01 Low Dose tapered/titrated over 34 days | Combination Product: PP-01 Low Dose<br>* CB1 partial agonist / GABAergic modulator<br>|
| Placebo Comparator: Placebo<br>Oral placebo, given daily for 34 days | Drug: Placebo<br>* Placebo comparator<br>|
| Active Comparator: Nabilone<br>oral nabilone, tapered/titrated over 28 days | Drug: Nabilone<br>* CB1 receptor<br>|
| Active Comparator: Gabapentin<br>oral gabapentin, tapered/titrated over 34 days | Drug: Gabapentin<br>* GABAergic modulator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of a patient reported outcome measure of cannabis withdrawal over 5 days |  | Over 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cannabis Use Disorder, Marijuana Use Disorder