Cannabis Use Disorder
Conditions
Brief summary
A Phase 2B, 8-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy, Safety and Tolerability of the Fatty Acid Amide Hydrolase (FAAH) Inhibitor PF-04457845 in Adults with DSM-5 Current Cannabis Use Disorder (CUD)
Detailed description
The efficacy, safety and tolerability of the FAAH Inhibitor PF-0447845 in reducing cannabis use will be studied in a 4-site randomized, double-blind, placebo-controlled, parallel-group, outpatient clinical trial comparing PF-04457845 (4mg) and placebo in DSM-5 CUD individuals. Participants will be randomized in a 1:1 ratio to either PF-04457845 or placebo using random block sizes of 2 and 4, stratified by site and degree of cannabis use. Participants will receive motivational interviewing for 2 weeks before being randomized to receive study medication to make a quit attempt within the first week of treatment. Participants will receive active or placebo PF-04457845 for 8 weeks during which time they will be evaluated weekly in face to face visits. In addition, daily assessment of adherence to study medication and cannabinoid use will be conducted daily by cellphone. Measures of cannabinoid exposure (self-reported and urine toxicology), and problems related to the use of cannabis, will be assessed.
Interventions
DRUGPF 04457845
Study medication will be administered at 4mg by mouth daily for eight weeks.
DRUGPlacebo Oral Tablet
Placebo comparator will be administered by mouth daily for eight weeks.
Sponsors
Columbia University
Johns Hopkins University
Medical University of South Carolina
National Institute on Drug Abuse (NIDA)
Yale University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Phase 2B
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Ages 18-60 years, inclusive. 2. Male or Female. 3. Individuals with DSM-V criteria for Cannabis Use Disorder . 4. Positive for urinary THC-COOH at both screening visits. 5. Must express a willingness at screening to set a date within the first week of randomization to attempt to quit using cannabis.
Exclusion criteria
1. Clinically significant unstable medical disorders (as determined by the site investigator). 2. Laboratory tests with clinically significant abnormalities (as determined by the site investigator) 3. Pregnancy by history and or laboratory confirmation (serum HCG). 4. Lactation. 5. Physiological dependence on another substance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time Line Follow Back (TLFB) for Cannabis Use | Change from baseline in self reported cannabis use as measured by the TLFB approach at baseline and then weekly average daily use over 8 weeks. | Change in the average number of times per day of self-reported cannabis consumption measured by the Timeline Follow Back approach for Cannabis Use in which participants quantify and report their frequency of cannabis use prior to study participation and throughout the study. Differences between groups in the change from baseline use (2 weeks prior to randomization) in the average number of times per day of self-reported consumption of cannabis or a cannabis containing product in the last 4 weeks of treatment captured using the daily TLFB data collected during CAROMA calls. |
| Urinary Levels of THC-COOH (ng/ml) | baseline, week 1, week 3, week 5, week 7, and week 9 visits | Assay of the levels of the principal metabolite of THC (THC-COOH) in urine samples at baseline and bi-weekly over 8 weeks. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PF-04457845 Subjects will be randomized to Fatty Acid Amide Hydrolase (FAAH) Inhibitor; 4 mg PF-04457845 QD x 8 weeks
PF 04457845: Study medication will be administered at 4mg by mouth daily for eight weeks. | 116 |
| Placebo Subjects will be randomized to placebo
Placebo Oral Tablet: Placebo comparator will be administered by mouth daily for eight weeks. | 112 |
| Total | 228 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 6 |
| Overall Study | Physician Decision | 11 | 8 |
| Overall Study | Withdrawal by Subject | 11 | 7 |
Baseline characteristics
| Characteristic | Placebo | Total | PF-04457845 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 112 Participants | 228 Participants | 116 Participants |
| Age, Continuous | 32.91 years STANDARD_DEVIATION 10.52 | 32.18 years STANDARD_DEVIATION 10.42 | 31.48 years STANDARD_DEVIATION 10.32 |
| Cannabis Use Severity (CUD) Moderate | 60 Participants | 123 Participants | 63 Participants |
| Cannabis Use Severity (CUD) Severe | 52 Participants | 105 Participants | 53 Participants |
| Education Associates Degree | 10 Participants | 25 Participants | 15 Participants |
| Education Bachelors Degree | 27 Participants | 55 Participants | 28 Participants |
| Education GED | 6 Participants | 12 Participants | 6 Participants |
| Education High School Diploma | 24 Participants | 48 Participants | 24 Participants |
| Education Less than High School Diploma | 3 Participants | 7 Participants | 4 Participants |
| Education Masters Degree | 8 Participants | 15 Participants | 7 Participants |
| Education Professional / Doctoral Degree | 1 Participants | 4 Participants | 3 Participants |
| Education Some College | 33 Participants | 62 Participants | 29 Participants |
| Employment Status Disabled, Permanently/Temp | 1 Participants | 1 Participants | 0 Participants |
| Employment Status Full-Time Job | 44 Participants | 98 Participants | 54 Participants |
| Employment Status Keeping House | 2 Participants | 2 Participants | 0 Participants |
| Employment Status Looking for Work, Unemployed | 18 Participants | 31 Participants | 13 Participants |
| Employment Status Other | 9 Participants | 18 Participants | 9 Participants |
| Employment Status Part-Time Job | 30 Participants | 59 Participants | 29 Participants |
| Employment Status Retired | 2 Participants | 3 Participants | 1 Participants |
| Employment Status Student | 5 Participants | 12 Participants | 7 Participants |
| Employment Status Temporarily Laid Off, On Leave | 1 Participants | 4 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 36 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 96 Participants | 192 Participants | 96 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Marital Status Divorced or Annulled | 5 Participants | 12 Participants | 7 Participants |
| Marital Status In a Relationship | 10 Participants | 20 Participants | 10 Participants |
| Marital Status In a Relationship & Living Together | 10 Participants | 22 Participants | 12 Participants |
| Marital Status Married | 20 Participants | 36 Participants | 16 Participants |
| Marital Status Never Married | 23 Participants | 45 Participants | 22 Participants |
| Marital Status Separated | 4 Participants | 8 Participants | 4 Participants |
| Marital Status Single | 40 Participants | 85 Participants | 45 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 53 Participants | 100 Participants | 47 Participants |
| Race (NIH/OMB) More than one race | 9 Participants | 22 Participants | 13 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 7 Participants | 6 Participants |
| Race (NIH/OMB) White | 45 Participants | 92 Participants | 47 Participants |
| Sex/Gender, Customized Female | 37 Participants | 84 Participants | 47 Participants |
| Sex/Gender, Customized Male | 75 Participants | 143 Participants | 68 Participants |
| Sex/Gender, Customized Transgender | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 116 | 0 / 112 |
| other Total, other adverse events | 89 / 116 | 91 / 112 |
| serious Total, serious adverse events | 2 / 116 | 0 / 112 |
Outcome results
Primary
Time Line Follow Back (TLFB) for Cannabis Use
Change in the average number of times per day of self-reported cannabis consumption measured by the Timeline Follow Back approach for Cannabis Use in which participants quantify and report their frequency of cannabis use prior to study participation and throughout the study. Differences between groups in the change from baseline use (2 weeks prior to randomization) in the average number of times per day of self-reported consumption of cannabis or a cannabis containing product in the last 4 weeks of treatment captured using the daily TLFB data collected during CAROMA calls.
Time frame: Change from baseline in self reported cannabis use as measured by the TLFB approach at baseline and then weekly average daily use over 8 weeks.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04457845 | Time Line Follow Back (TLFB) for Cannabis Use | Week 1 | 1.921 times/day of self-reported cannabis use | Standard Deviation 1.538 |
| PF-04457845 | Time Line Follow Back (TLFB) for Cannabis Use | Week 2 | 1.201 times/day of self-reported cannabis use | Standard Deviation 1.638 |
| PF-04457845 | Time Line Follow Back (TLFB) for Cannabis Use | Week 3 | 1.308 times/day of self-reported cannabis use | Standard Deviation 1.881 |
| PF-04457845 | Time Line Follow Back (TLFB) for Cannabis Use | Week 4 | 1.316 times/day of self-reported cannabis use | Standard Deviation 1.956 |
| PF-04457845 | Time Line Follow Back (TLFB) for Cannabis Use | Week 5 | 1.234 times/day of self-reported cannabis use | Standard Deviation 1.8 |
| PF-04457845 | Time Line Follow Back (TLFB) for Cannabis Use | Week 6 | 1.252 times/day of self-reported cannabis use | Standard Deviation 1.639 |
| PF-04457845 | Time Line Follow Back (TLFB) for Cannabis Use | Week 7 | 1.321 times/day of self-reported cannabis use | Standard Deviation 1.762 |
| PF-04457845 | Time Line Follow Back (TLFB) for Cannabis Use | Week 8 | 1.113 times/day of self-reported cannabis use | Standard Deviation 1.481 |
| Placebo | Time Line Follow Back (TLFB) for Cannabis Use | Week 8 | 0.936 times/day of self-reported cannabis use | Standard Deviation 1.417 |
| Placebo | Time Line Follow Back (TLFB) for Cannabis Use | Week 1 | 1.768 times/day of self-reported cannabis use | Standard Deviation 1.758 |
| Placebo | Time Line Follow Back (TLFB) for Cannabis Use | Week 5 | 1.214 times/day of self-reported cannabis use | Standard Deviation 2.22 |
| Placebo | Time Line Follow Back (TLFB) for Cannabis Use | Week 2 | 1.066 times/day of self-reported cannabis use | Standard Deviation 1.702 |
| Placebo | Time Line Follow Back (TLFB) for Cannabis Use | Week 7 | 0.91 times/day of self-reported cannabis use | Standard Deviation 1.3 |
| Placebo | Time Line Follow Back (TLFB) for Cannabis Use | Week 3 | 1.06 times/day of self-reported cannabis use | Standard Deviation 1.663 |
| Placebo | Time Line Follow Back (TLFB) for Cannabis Use | Week 6 | 1.079 times/day of self-reported cannabis use | Standard Deviation 1.645 |
| Placebo | Time Line Follow Back (TLFB) for Cannabis Use | Week 4 | 0.998 times/day of self-reported cannabis use | Standard Deviation 1.414 |
Primary
Urinary Levels of THC-COOH (ng/ml)
Assay of the levels of the principal metabolite of THC (THC-COOH) in urine samples at baseline and bi-weekly over 8 weeks.
Time frame: baseline, week 1, week 3, week 5, week 7, and week 9 visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PF-04457845 | Urinary Levels of THC-COOH (ng/ml) | Screening | 5.959 ng/ml | Standard Deviation 6.633 |
| PF-04457845 | Urinary Levels of THC-COOH (ng/ml) | Week 1 | 5.077 ng/ml | Standard Deviation 4.837 |
| PF-04457845 | Urinary Levels of THC-COOH (ng/ml) | Week 3 | 3.069 ng/ml | Standard Deviation 3.385 |
| PF-04457845 | Urinary Levels of THC-COOH (ng/ml) | Week 5 | 3.482 ng/ml | Standard Deviation 5.064 |
| PF-04457845 | Urinary Levels of THC-COOH (ng/ml) | Week 7 | 3.241 ng/ml | Standard Deviation 5.67 |
| PF-04457845 | Urinary Levels of THC-COOH (ng/ml) | Week 9 | 3.222 ng/ml | Standard Deviation 3.913 |
| Placebo | Urinary Levels of THC-COOH (ng/ml) | Week 7 | 4.223 ng/ml | Standard Deviation 7.724 |
| Placebo | Urinary Levels of THC-COOH (ng/ml) | Screening | 5.571 ng/ml | Standard Deviation 6.542 |
| Placebo | Urinary Levels of THC-COOH (ng/ml) | Week 5 | 4.465 ng/ml | Standard Deviation 7.411 |
| Placebo | Urinary Levels of THC-COOH (ng/ml) | Week 1 | 5.747 ng/ml | Standard Deviation 7.456 |
| Placebo | Urinary Levels of THC-COOH (ng/ml) | Week 9 | 3.952 ng/ml | Standard Deviation 7.511 |
| Placebo | Urinary Levels of THC-COOH (ng/ml) | Week 3 | 3.92 ng/ml | Standard Deviation 6.673 |