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Clavulanic Acid (CLAV) and Cocaine Interaction Safety Study

Primary Purpose

Cocaine Dependence, Cocaine Addiction, Cocaine Abuse

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Clavulanic acid
Intravenous cocaine
Placebo
Sponsored by
Temple University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cocaine Dependence focused on measuring Cocaine, Clavulanic Acid

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Meet DSM-5 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.)

Sites / Locations

  • Temple University Hospital - Episcopal Campus

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Treatment Arm 1

Treatment Arm 2

Treatment Arm 3

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

Rates of Occurrence of Adverse Events (AEs) as a Measure of Safety and Tolerability of Clavulanic Acid (CLAV)
Safety and toleration as assessed by the rates of occurrence of adverse events across the three study periods within each subject.
Changes in Cardiovascular Responses as a Measure of Safety and Tolerability of Clavulanic Acid (CLAV)
Cardiovascular responses induced by cocaine infusion will be compared to cardiovascular response measurements before the cocaine infusion to assess change. Cardiovascular changes after infusion given after CLAV (250 mg, 500 mg) will be compared to those without CLAV. We will compare the distribution of Area Under Curve (AUC) summaries of the within-period repeated measures of changes in vital signs (heart rate, systolic blood pressure, diastolic blood pressure) across the three-periods within each person.

Secondary Outcome Measures

Pharmacokinetic (PK) Parameter of Cocaine and its major metabolite, benzoylecgonine (BE): Maximum Observed Concentration (Cmax)
PK parameters of cocaine alone will be compared statistically with parameters when both cocaine and clavulanic acid (250 mg, 500 mg) are present. Cmax = Maximum observed concentration
PK Parameter of Clavulanic Acid (CLAV): Maximum Observed Concentration (Cmax)
PK parameters of clavulanic acid alone will be compared statistically at both doses of clavulanic acid (250 mg, 500 mg). Cmax = Maximum observed concentration
Pharmacodynamic Effects of Cocaine and Clavulanic Acid
Pupil Diameter (over time) after cocaine infusion alone (with placebo) will be compared with pupil diameter (over time) after cocaine infusion with clavulanic acid at both doses (250 mg, 500 mg).

Full Information

First Posted
August 6, 2015
Last Updated
July 6, 2018
Sponsor
Temple University
Collaborators
National Institute on Drug Abuse (NIDA), University of Pennsylvania
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1. Study Identification

Unique Protocol Identification Number
NCT02563769
Brief Title
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

2. Study Status

Record Verification Date
July 2018
Overall Recruitment Status
Completed
Study Start Date
September 2016 (Actual)
Primary Completion Date
May 25, 2018 (Actual)
Study Completion Date
May 25, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Temple University
Collaborators
National Institute on Drug Abuse (NIDA), University of Pennsylvania

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cocaine Dependence, Cocaine Addiction, Cocaine Abuse, Cocaine-Related Disorders
Keywords
Cocaine, Clavulanic Acid

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm 1
Arm Type
Experimental
Arm Description
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
Arm Title
Treatment Arm 2
Arm Type
Experimental
Arm Description
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
Arm Title
Treatment Arm 3
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Clavulanic acid
Intervention Type
Drug
Intervention Name(s)
Intravenous cocaine
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Rates of Occurrence of Adverse Events (AEs) as a Measure of Safety and Tolerability of Clavulanic Acid (CLAV)
Description
Safety and toleration as assessed by the rates of occurrence of adverse events across the three study periods within each subject.
Time Frame
6 Days (Study Days 1, 2, 3, 4, 5, 10)
Title
Changes in Cardiovascular Responses as a Measure of Safety and Tolerability of Clavulanic Acid (CLAV)
Description
Cardiovascular responses induced by cocaine infusion will be compared to cardiovascular response measurements before the cocaine infusion to assess change. Cardiovascular changes after infusion given after CLAV (250 mg, 500 mg) will be compared to those without CLAV. We will compare the distribution of Area Under Curve (AUC) summaries of the within-period repeated measures of changes in vital signs (heart rate, systolic blood pressure, diastolic blood pressure) across the three-periods within each person.
Time Frame
5 Days (Study Days 1, 2, 3, 4, 5)
Secondary Outcome Measure Information:
Title
Pharmacokinetic (PK) Parameter of Cocaine and its major metabolite, benzoylecgonine (BE): Maximum Observed Concentration (Cmax)
Description
PK parameters of cocaine alone will be compared statistically with parameters when both cocaine and clavulanic acid (250 mg, 500 mg) are present. Cmax = Maximum observed concentration
Time Frame
4 Days (Study Days 2, 3, 4, 5)
Title
PK Parameter of Clavulanic Acid (CLAV): Maximum Observed Concentration (Cmax)
Description
PK parameters of clavulanic acid alone will be compared statistically at both doses of clavulanic acid (250 mg, 500 mg). Cmax = Maximum observed concentration
Time Frame
4 Days (Study Days 2, 3, 4, 5)
Title
Pharmacodynamic Effects of Cocaine and Clavulanic Acid
Description
Pupil Diameter (over time) after cocaine infusion alone (with placebo) will be compared with pupil diameter (over time) after cocaine infusion with clavulanic acid at both doses (250 mg, 500 mg).
Time Frame
4 Days (Study Days 1, 2, 3, 4, 5)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Meet DSM-5 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.)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kyle M. Kampman, M.D.
Organizational Affiliation
U54 Principal Investigator - University of Pennsylvania
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mary F. Morrison, M.D., M.S.
Organizational Affiliation
Temple University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
M. I Walters, M.D.
Organizational Affiliation
Temple University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Temple University Hospital - Episcopal Campus
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19125
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
19128205
Citation
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.
Results Reference
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PubMed Identifier
20383795
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.
Results Reference
background
PubMed Identifier
21543969
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.
Results Reference
background
PubMed Identifier
23031254
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.
Results Reference
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Clavulanic Acid (CLAV) and Cocaine Interaction Safety Study

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