Effect of PP-01 on Cannabis Withdrawal Syndrome

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

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).

Study Overview

• Status: Completed
• Conditions: Cannabis Withdrawal
• Intervention / Treatment: Drug: Placebo; Combination product: PP-01 High Dose; Combination product: PP-01 Low Dose; Drug: Nabilone; Drug: Gabapentin

• Study Type: Interventional
• Enrollment (Actual): 234
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Behavioral Research Specialists, LLC
    • Lemon Grove, California, United States, 91945
      • Synergy San Diego
    • Orange, California, United States, 92868
      • Neuropsychiatric Research Institute
  • Florida
    • Coral Springs, Florida, United States, 33067
      • CNS Clinical Research Group
    • Fort Myers, Florida, United States, 33912
      • Gulf Coast Clinical Research
    • Lauderhill, Florida, United States, 33319
      • Innovative Clinical Research Inc.
  • Georgia
    • Decatur, Georgia, United States, 30030
      • CenExel iResearch Atlanta, LLC
    • Savannah, Georgia, United States, 31405
      • CenExel iResearch Savannah, LLC
  • Illinois
    • Chicago, Illinois, United States, 60641
      • Pillar Clinical Research, LLC
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Otrimed Research Center
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Tandem Clinical Research
    • Shreveport, Louisiana, United States, 71101
      • Benchmark Research
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
  • Ohio
    • Middleburg Heights, Ohio, United States, 44130
      • North Star Medical Research
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Pahl Pharmaceutical Professionals Llc
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Medical University of South Carolina
  • Texas
    • Austin, Texas, United States, 78744
      • Austin Clinical Trials
  • Utah
    • Draper, Utah, United States, 84020
      • Cedar Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Generally healthy individuals between the ages of 18 and 55, inclusive
2. 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
3. BMI within 18.0 to 38.0 kg/m2, inclusive
4. Seeking to minimize withdrawal symptoms related to cannabis discontinuation in people seeking to discontinue cannabis
5. Meet DSM-5 Cannabis Withdrawal
6. Report heavy use of daily/near daily cannabis
7. Have a urine drug screen positive for tetrahydrocannabinol (THC)/THC metabolites at Screening and Randomization
8. Capable of giving informed consent and complying with study procedures
9. 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:

1. Lifetime history of DSM-5 diagnosis of schizophrenia or schizoaffective disorder, or Bipolar 1 within the previous 2 years
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 substance use disorder other than cannabis, nicotine, or caffeine use disorders
4. Participants using cannabis for a medical condition requiring use such as epilepsy
5. Clinically significant unstable medical disorders
6. Any clinically important abnormalities on Screening physical examination (PE), assessments, ECG, or laboratory tests
7. Use of an investigational drug or biologic within 30 days or 5 times the half-life (whichever is longer) prior to the Screening Visit
8. Pregnant or lactating female participants, or a positive urine pregnancy test
9. COVID-19

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: PleoPharma, Inc.
• Investigators: Study Director: Jay Constantine, MD, PleoPharma, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2022
• Primary Completion (Actual): August 21, 2023
• Study Completion (Actual): August 21, 2023

Study Registration Dates

• First Submitted: August 8, 2022
• First Submitted That Met QC Criteria: August 8, 2022
• First Posted (Actual): August 10, 2022

Study Record Updates

• Last Update Posted (Actual): August 16, 2024
• Last Update Submitted That Met QC Criteria: August 14, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Cannabis Use Disorder; Marijuana Use Disorder
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Marijuana Abuse; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Antiemetics; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Anti-Anxiety Agents; Anticonvulsants; Antimanic Agents; Gabapentin; Nabilone
• Other Study ID Numbers: CAN-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes