Clinical trial NCT02563769: Clavulanic Acid (CLAV) and Cocaine Interaction Safety Study
Official title: Phase 1, Double-Blind, Placebo-Controlled Assessment of Potential Interactions Between Intravenous Cocaine and Clavulanic Acid
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cocaine Dependence
Cocaine Addiction
Cocaine Abuse
Cocaine-Related Disorders
Keywords: Cocaine
Clavulanic Acid
Lead sponsor: Temple University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
name: University of Pennsylvania
First posted: 2015-09-30
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to determine if it is safe to use the study drug, clavulanic acid, in combination with cocaine. In this study, subjects will receive intravenous (i.v.) cocaine and the study drug, clavulanic acid. The safety of clavulanic acid is being studied so future studies can be done to find out if this drug is helpful in treating cocaine dependence. Currently, there is no available medication treatment for cocaine dependence.

Detailed description: This is a prospective, placebo controlled inpatient crossover safety study of 3 doses (250 mg/day, 500 mg/day, 750 mg/day) of CLAV with an intravenous infusion of cocaine 40 mg. Subjects will be non-treatment seeking experienced cocaine dependent adults, ages 18-65 (N=12 completers, 21 estimated to enroll). Subjects will undergo a washout of the study drug for 5 half-lives between study drug administration sessions.

The primary objective will be to determine whether there are clinically significant adverse interactions between CLAV (250 mg/day; 500 mg/day; 750 mg/day) and intravenously administered cocaine in healthy, non-treatment seeking adults with cocaine use disorder.

Eligibility criteria: Inclusion Criteria:

* Meet Diagnostic and Statistical Manual of Mental Disorders Fifth Edition criteria for cocaine use disorder, moderate to severe.
* Be a non-treatment seeking cocaine user.
* If female and of childbearing potential, must have a negative pregnancy test within 48 hours of beginning the study and be willing to use acceptable contraception or be abstinent for 14 days prior to study, through the entire study and 30 days after study participation.

Exclusion Criteria:

* Be seeking treatment for substance abuse.

(For full inclusion/exclusion criteria or for more information, please contact the site directly.)

Primary outcomes:
measure: Number of Participants With Severe Adverse Events (AEs)
timeFrame: 6 Days (Study Days 1, 2, 3, 4, 5, 10)
measure: Change in Heart Rate in Response to IV Cocaine Infusion With and Without CLAV Dosing
timeFrame: 4 Days (Study Days 2, 3, 4, 5)
measure: Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing
timeFrame: 4 Days (Study Days 2, 3, 4, 5)
measure: Electrocardiogram (ECG) Following IV Cocaine With and Without CLAV Dosing
timeFrame: 4 Days (Study Days 2, 3, 4, 5)
Secondary outcomes:
measure: Pharmacokinetic (PK) Parameter of Cocaine-concentration
timeFrame: 3 Days (Study Days 2, 3, 4)
measure: Clavulanic Acid (CLAV) Concentrations Following CLAV 250mg and CLAV 500mg Doses
timeFrame: 3 Days (Study Days 2, 3, 4)
measure: Difference in CLAV Concentrations Between the 250mg and 500mg CLAV Doses
timeFrame: 3 days (Day 2, 3, 4)
measure: Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid
timeFrame: 10 minutes pre-infusion and 10, 15, 30 and 45 min after cocaine infusion on Study Days 2, 3, and 4
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Temple University Hospital - Episcopal Campus
state: Pennsylvania
Study officials:
affiliation: U54 Principal Investigator - University of Pennsylvania
name: Kyle M. Kampman, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Temple University
name: Mary F. Morrison, M.D., M.S.
role: PRINCIPAL_INVESTIGATOR
affiliation: Temple University
name: M. I Walters, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Rasmussen BA, Baron DA, Kim JK, Unterwald EM, Rawls SM. beta-Lactam antibiotic produces a sustained reduction in extracellular glutamate in the nucleus accumbens of rats. Amino Acids. 2011 Feb;40(2):761-4. doi: 10.1007/s00726-010-0589-0. Epub 2010 Apr 13.
citation: Ward SJ, Rasmussen BA, Corley G, Henry C, Kim JK, Walker EA, Rawls SM. Beta-lactam antibiotic decreases acquisition of and motivation to respond for cocaine, but not sweet food, in C57Bl/6 mice. Behav Pharmacol. 2011 Aug;22(4):370-3. doi: 10.1097/FBP.0b013e3283473c10.
citation: Kovalevich J, Corley G, Yen W, Rawls SM, Langford D. Cocaine-induced loss of white matter proteins in the adult mouse nucleus accumbens is attenuated by administration of a beta-lactam antibiotic during cocaine withdrawal. Am J Pathol. 2012 Dec;181(6):1921-7. doi: 10.1016/j.ajpath.2012.08.013. Epub 2012 Sep 29.