Clavulanic Acid (CLAV) and Cocaine Interaction Safety Study

NCT ID: NCT02563769

Last Updated: 2023-11-03

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-10-24

Study Completion Date

2018-05-25

Brief Summary

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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

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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.

Conditions

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Cocaine Dependence Cocaine Addiction Cocaine Abuse Cocaine-Related Disorders

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Clavulanic Acid (CLAV) 250mg; CLAV 500mg then Placebo (PBO)

Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Clavulanic Acid 250 mg (low dose); Day #3: Clavulanic Acid 500 mg; Day #4: Placebo

Group Type EXPERIMENTAL

Clavulanic acid

Intervention Type DRUG

Clavulanic acid will be administered orally in 250mg capsules

Intravenous cocaine

Intervention Type DRUG

20/40mg Cocaine will be administered by IV

Placebo

Intervention Type DRUG

Placebo will be administered orally in capsules identical to CLAV and be filled with crystalline microcellulose

CLAV 250mg; PBO; then CLAV 500mg

Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Clavulanic Acid 250 mg (low dose); Day #3: Placebo; Day #4: Clavulanic Acid 500 mg

Group Type EXPERIMENTAL

Clavulanic acid

Intervention Type DRUG

Clavulanic acid will be administered orally in 250mg capsules

Intravenous cocaine

Intervention Type DRUG

20/40mg Cocaine will be administered by IV

Placebo

Intervention Type DRUG

Placebo will be administered orally in capsules identical to CLAV and be filled with crystalline microcellulose

PBO; CLAV 250mg; then CLAV 500mg

Clavulanic acid OR Placebo to be given in combination with intravenous cocaine; Day #2: Placebo; Day #3: Clavulanic Acid 250 mg (low dose); Day #4: Clavulanic Acid 500 mg

Group Type EXPERIMENTAL

Clavulanic acid

Intervention Type DRUG

Clavulanic acid will be administered orally in 250mg capsules

Intravenous cocaine

Intervention Type DRUG

20/40mg Cocaine will be administered by IV

Placebo

Intervention Type DRUG

Placebo will be administered orally in capsules identical to CLAV and be filled with crystalline microcellulose

Interventions

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Clavulanic acid

Clavulanic acid will be administered orally in 250mg capsules

Intervention Type DRUG

Intravenous cocaine

20/40mg Cocaine will be administered by IV

Intervention Type DRUG

Placebo

Placebo will be administered orally in capsules identical to CLAV and be filled with crystalline microcellulose

Intervention Type DRUG

Other Intervention Names

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CLAV Coc PBO

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

University of Pennsylvania

OTHER

Sponsor Role collaborator

Temple University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kyle M. Kampman, M.D.

Role: PRINCIPAL_INVESTIGATOR

U54 Principal Investigator - University of Pennsylvania

Mary F. Morrison, M.D., M.S.

Role: PRINCIPAL_INVESTIGATOR

Temple University

M. I Walters, M.D.

Role: PRINCIPAL_INVESTIGATOR

Temple University

Locations

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Temple University Hospital - Episcopal Campus

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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Uys JD, LaLumiere RT. Glutamate: the new frontier in pharmacotherapy for cocaine addiction. CNS Neurol Disord Drug Targets. 2008 Nov;7(5):482-91. doi: 10.2174/187152708786927868.

Reference Type BACKGROUND
PMID: 19128205 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20383795 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21543969 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23031254 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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1U54DA039002-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

23222

Identifier Type: -

Identifier Source: org_study_id

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