Effect of PP-01 on Cannabis Withdrawal Syndrome

Recruiting at 18 trial locations

Overseen By PleoPharma, Inc CMO, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: PleoPharma, Inc.

Must not be taking: Psychotropics

Disqualifiers: Schizophrenia, Bipolar, Other substance use, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 7

Duration: 5 weeks

234 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a medication called PP-01 to see if it can help people with severe cannabis use disorder feel better when they quit using cannabis. The study involves 225 participants and aims to reduce the uncomfortable withdrawal symptoms they experience.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on stable psychotropic medication for at least 3 months, you may be included at the investigator's discretion.

What safety data exists for the treatment known as PP-01?

The safety of treatments in phase I clinical trials, which often include healthy volunteers, is generally monitored for adverse events (unwanted effects). A study analyzing 142 phase I trials found that adverse events do occur, but the frequency and seriousness can vary. It's important to note that safety reporting in clinical trials can sometimes be inconsistent, and efforts are being made to improve the standardization and thoroughness of safety data collection. ^{1 2 3 4 5}

How does the drug PP-01 differ from other treatments for this condition?

PP-01 is unique because it involves protein phosphatase one (PP1), which is a key enzyme that regulates various cellular processes by removing phosphate groups from proteins. This mechanism of action is different from many other treatments that may not target protein dephosphorylation. ^{6 7 8 9 10}

Research Team

Jay Constantine, MD

Principal Investigator

PleoPharma, Inc.

Eligibility Criteria

Inclusion Criteria

Your body mass index (BMI) falls between 18.0 and 38.0 kg/m2.

Report heavy use of daily/near daily cannabis

Have a urine drug screen positive for tetrahydrocannabinol (THC)/THC metabolites at Screening and Randomization

Exclusion Criteria

You have been diagnosed with schizophrenia or schizoaffective disorder or bipolar 1 within the past 2 years.

You have a mental health condition that is currently unstable or may be affected by the study medication. If you have been taking medication for a stable condition for at least 3 months, the Investigator may decide to include you in the study.

You have a serious medical condition that is not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive study medication for 34 days to mitigate cannabis withdrawal symptoms

5 weeks

7 visits (in-person), 4 visits (telemedicine)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• PP-01

Participant Groups

Group I: PP-01 Low Dose Experimental Treatment 1 Intervention

Oral PP-01 Low Dose tapered/titrated over 34 days

Group II: PP-01 High Dose Experimental Treatment 1 Intervention

Oral PP-01 High Dose tapered/titrated over 34 days

Group III: Nabilone Active Control 1 Intervention

oral nabilone, tapered/titrated over 28 days

Group IV: Gabapentin Active Control 1 Intervention

oral gabapentin, tapered/titrated over 34 days

Group V: Placebo Placebo Group 1 Intervention

Oral placebo, given daily for 34 days

Who Is Running the Clinical Trial?

PleoPharma, Inc.

Lead Sponsor

Trials

1

Recruited

230+

Findings from Research

In a meta-analysis of 11,028 healthy participants across 394 non-oncology phase I studies, 63.7% experienced adverse events, but 85% of these were classified as mild, indicating a relatively safe profile for the study drugs.

Only 0.31% of participants experienced serious adverse events, with no deaths or life-threatening incidents reported, suggesting that while adverse events are common, they are mostly not severe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantifying the risks of non-oncology phase I research in healthy volunteers: meta-analysis of phase I studies. Emanuel, EJ., Bedarida, G., Macci, K., et al.[2018]

A review of 192 randomized clinical trials revealed that safety information is often underreported, with only 46% specifying reasons for withdrawals due to toxicity and only 39% adequately reporting clinical adverse effects.

To enhance safety reporting, the study emphasizes the need for standardized scales for adverse effects, systematic data collection, and detailed reporting of severe reactions, suggesting that improved practices could lead to better safety insights in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving safety reporting from randomised trials. Ioannidis, JP., Lau, J.[2018]

In a five-year analysis of 1,559 healthy volunteers across 142 phase I studies, the overall incidence of adverse events (AEs) was 8.8%, with most AEs being mild or moderate in severity, indicating that while AEs are common, they are generally not severe.

The incidence of AEs was significantly higher in multiple-dose studies compared to single-dose trials, highlighting the importance of study design in assessing the safety profile of active drugs, with a notable increase in AEs on the first day of drug administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in volunteers participating in phase I clinical trials: a single-center five-year survey in 1,559 subjects. Lutfullin, A., Kuhlmann, J., Wensing, G.[2019]

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

The review of clinical research data from 1977 to 2011 highlights significant inconsistencies in how adverse reactions (AR) to drugs are assessed, which can affect the reliability of safety information provided to patients.

To improve the safety profiles of medications, the authors advocate for the establishment of a common European standard for the structured assessment of adverse reactions in clinical research, as no such standard currently exists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Assessing adverse reactions in clinical trials]. Harnisch, S., Schade-Brittinger, C., Rief, W.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Quantifying the risks of non-oncology phase I research in healthy volunteers: meta-analysis of phase I studies. [2018]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Improving safety reporting from randomised trials. [2018]

3. Germany pubmed.ncbi.nlm.nih.gov

Adverse events in volunteers participating in phase I clinical trials: a single-center five-year survey in 1,559 subjects. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

[Assessing adverse reactions in clinical trials]. [2013]

6. England pubmed.ncbi.nlm.nih.gov

Displacement affinity chromatography of protein phosphatase one (PP1) complexes. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Towards a comprehensive analysis of the protein phosphatase 1 interactome in Drosophila. [2015]

8. England pubmed.ncbi.nlm.nih.gov

Phosphorylation of the high-mobility-group-like protein P1 by casein kinase-2. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Protein phosphatase-1alpha regulates centrosome splitting through Nek2. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

The direct binding of the catalytic subunit of protein phosphatase 1 to the PKR protein kinase is necessary but not sufficient for inactivation and disruption of enzyme dimer formation. [2021]