Clavulanic Acid for the Treatment of Cocaine Use Disorder

Study Overview
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Brief Summary
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A dose escalation study to assess the efficacy and safety of Clavulanic Acid (CLAV) vs. placebo (PBO) for the treatment of cocaine use disorder (CUD)

Detailed Description
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This pilot study is indicated for treatment of moderate to severe cocaine use disorder. It is a randomized, placebo-controlled, parallel group, multi-center pilot study to compare the efficacy of 500-750mg/day clavulanic acid vs. placebo in addition to weekly medication management therapy. Subjective, cognitive, and adverse effect assessments, blood pressure and pulse will be performed 1-3 times weekly.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Phase 2a Pilot Study to Assess the Efficacy and Safety of Clavulanic Acid vs. Placebo for the Treatment of Cocaine Use Disorder

Conditions
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Cocaine Dependence

Intervention / Treatment
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* Drug: Clavulanic Acid Only Product
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be able to verbalize understanding of consent form, able to provide written informed consent, and verbalize willingness to complete study procedures Be male or female adult volunteers ages 18-70 inclusive. Have a Diagnostic and Statistical Manual (DSM-V) diagnosis of cocaine use disorder, moderate to severe in early remission with a duration of regular (weekly or more) cocaine (either snorted, smoked or injected) for at least one year. Have a history and brief physical examination that demonstrate no clinically significant contraindication for participating in the study, and/ or significant or unstable medical or psychiatric illness. Exclusion Criteria: Meets DSM-V criteria for dependence on any substance other than cocaine and mild to moderate alcohol or marijuana (except nicotine or caffeine), determined by the structured clinical interview for DSM-V. Allergy to clavulanic acid, penicillin, or any beta-lactam drug. Meets current or lifetime DSM-V criteria for schizophrenia or any psychotic disorder or organic mental disorder. Subject meets current DSM-V diagnosis of any other clinically significant psychiatric disorder that will interfere with study participation. Severe physical or medical illnesses such as AIDS or active hepatitis. If female, tests positive on a pregnancy test, is contemplating pregnancy in the next 6 months, is nursing, or is not using an effective contraceptive method (if relevant)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: Randomized, double-blind, placebo-controlled, parallel group study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clavulanic Acid<br>Participants may receive 500 mg of CLAV at baseline. Subjects who are using cocaine once per week or more and who can tolerate 500 mg/day for 4 weeks, will have a dose escalation to 750 mg/day. If tolerated, 750mg/day will be maintained for 8 weeks, otherwise the dose will decrease to 500mg/day. | Drug: Clavulanic Acid Only Product<br>* Drug will be given in 250mg capsules<br>|
| Placebo Comparator: Placebo<br>Participants may receive placebo and serve as a control group. They will be blinded to their condition and will have a dose escalation at the same time as the experimental group, and be given additional placebo pills to match the number given to the experimental group. | Drug: Placebo<br>* Capsule with no active medication - identical to drug capsule<br>* Other names: microcrystalline cellulose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in relapse to cocaine use in CLAV group vs PBO group | Cocaine-free weeks are measured by self-report using Timeline Follow Back (TLFB) and confirmed by urine drug screen. | Last 3 weeks of 12 week study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in weekly abstinence in the CLAV group vs. PBO group | Abstinence from cocaine by week will be measured by self report and urine drug screen | Self reported cocaine use and Urine Drug Screen (UDS) will be administered 1-3 times per week and at follow-up | 
| Changes in weekly cocaine use will be greater in the CLAV group vs. PBO group | Cocaine-free visits are measured by self-report using TLFB confirmed by urine drug screen | TLFB and UDS will be administered 1-3 times per week and at follow-up | 
| Changes in subject health and function, quality-of-life, will be greater in the CLAV group vs. PBO group | Medical Outcomes Study Quality of Life Scale short form 36, will determine whether CLAV treatment is associated with improved QOL | Baseline, week 4, week 8, week 12 | 
| Clavulanic acid 500-750 mg/day for 12 weeks will be safe and reasonably well tolerated | Safety and tolerability as assessed by the rates of occurrence of adverse events (AEs) and the severity | 1-3 times per week and at follow-up | 
| Cocaine craving will be decreased more by CLAV vs. PBO | Changes in craving will be greater in the CLAV group compared with PBO group, as measured by the cocaine craving questionnaire (CCQ), adjusted for baseline and sex | 1-3 times per week and at follow-up |