NCT02563769

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
10

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Oct 2016

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 6, 2015

Completed
2 months until next milestone

First Posted

Study publicly available on registry

September 30, 2015

Completed
1.1 years until next milestone

Study Start

First participant enrolled

October 24, 2016

Completed
1.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 25, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 25, 2018

Completed
5.4 years until next milestone

Results Posted

Study results publicly available

November 3, 2023

Completed
Last Updated

November 3, 2023

Status Verified

October 1, 2023

Enrollment Period

1.6 years

First QC Date

August 6, 2015

Results QC Date

August 11, 2022

Last Update Submit

October 11, 2023

Conditions

Cocaine DependenceCocaine AddictionCocaine AbuseCocaine-Related Disorders

Keywords

CocaineClavulanic Acid

Outcome Measures

Primary Outcomes (4)

  • Number of Participants With Severe Adverse Events (AEs)

    Rates of occurrence of serious adverse events across the different treatments: Day 1-IV cocaine only; Day 2.3 and 4 treatment with either PBO, CLAV 250mg or CLAV 500mg depending on randomization; Day 5 CLAV 750mg, Day 10 Follow-up appointment See Adverse Event section for reporting of mild-moderate AEs.

    6 Days (Study Days 1, 2, 3, 4, 5, 10)

  • Change in Heart Rate in Response to IV Cocaine Infusion With and Without CLAV Dosing

    IV cocaine was infused 1 hour following the dosing of PBO or CLAV 250mg, CLAV 500mg and CLAV 750 mg and vital signs were checked at -15min,-10min, -5 min preinfusion of IV cocaine and then every 2 min for the first 30 minutes, then every 15min through 150 minutes post-infusion. The mean heart rate (HR) at 2 minutes post IV cocaine infusion and the maximum (max) change in heart rate from baseline pre-infusion are reported (peak heart rate post-infusion minus baseline heart rate pre-infusion) are reported.

    4 Days (Study Days 2, 3, 4, 5)

  • Changes in Blood Pressure in Response to IV Cocaine With and Without CLAV Dosing

    IV cocaine was infused 1 hour following the dosing of PBO or CLAV 250mg, CLAV 500mg and CLAV 750 mg and vital signs were checked at -15min,-10min, -5 min pre-infusion of IV cocaine and then every 2 min for the first 30 minutes, then every 15min through 150 minutes post-infusion. The mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) at 2 minutes post IV cocaine infusion are reported. Also, the maximum (max) change in SBP snd DBP from baseline pre-infusion are reported (peak SBP or DBP post-infusion minus baseline SBP or DBP pre-infusion) are reported.

    4 Days (Study Days 2, 3, 4, 5)

  • Electrocardiogram (ECG) Following IV Cocaine With and Without CLAV Dosing

    ECG was done 15 min after IV cocaine infusion (following the dosing of PBO or CLAV 250mg, CLAV 500mg and CLAV 750 mg). The interval between the Q wave and the T wave, corrected (QTc) is reported.

    4 Days (Study Days 2, 3, 4, 5)

Secondary Outcomes (4)

  • Pharmacokinetic (PK) Parameter of Cocaine-concentration

    3 Days (Study Days 2, 3, 4)

  • Clavulanic Acid (CLAV) Concentrations Following CLAV 250mg and CLAV 500mg Doses

    3 Days (Study Days 2, 3, 4)

  • Difference in CLAV Concentrations Between the 250mg and 500mg CLAV Doses

    3 days (Day 2, 3, 4)

  • Pupil Pharmacodynamic Effects of Cocaine With Clavulanic Acid

    10 minutes pre-infusion and 10, 15, 30 and 45 min after cocaine infusion on Study Days 2, 3, and 4

Study Arms (3)

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

EXPERIMENTAL

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

Drug: Clavulanic acidDrug: Intravenous cocaineDrug: Placebo

CLAV 250mg; PBO; then CLAV 500mg

EXPERIMENTAL

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

Drug: Clavulanic acidDrug: Intravenous cocaineDrug: Placebo

PBO; CLAV 250mg; then CLAV 500mg

EXPERIMENTAL

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

Drug: Clavulanic acidDrug: Intravenous cocaineDrug: Placebo

Interventions

Clavulanic acidDRUG

Clavulanic acid will be administered orally in 250mg capsules

Also known as: CLAV
CLAV 250mg; PBO; then CLAV 500mgClavulanic Acid (CLAV) 250mg; CLAV 500mg then Placebo (PBO)PBO; CLAV 250mg; then CLAV 500mg
Intravenous cocaineDRUG

20/40mg Cocaine will be administered by IV

Also known as: Coc
CLAV 250mg; PBO; then CLAV 500mgClavulanic Acid (CLAV) 250mg; CLAV 500mg then Placebo (PBO)PBO; CLAV 250mg; then CLAV 500mg
PlaceboDRUG

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

Also known as: PBO
CLAV 250mg; PBO; then CLAV 500mgClavulanic Acid (CLAV) 250mg; CLAV 500mg then Placebo (PBO)PBO; CLAV 250mg; then CLAV 500mg

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • Be seeking treatment for substance abuse.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Temple University Hospital - Episcopal Campus

Philadelphia, Pennsylvania, 19125, United States

Location

Related Publications (4)

  • 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.

    PMID: 19128205BACKGROUND

  • 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.

    PMID: 20383795BACKGROUND

  • 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.

    PMID: 21543969BACKGROUND

  • 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.

    PMID: 23031254BACKGROUND

MeSH Terms

Conditions

Cocaine-Related Disorders

Interventions

Clavulanic Acid

Condition Hierarchy (Ancestors)

Substance-Related DisordersChemically-Induced DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Clavulanic Acidsbeta-LactamsLactamsAmidesOrganic ChemicalsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Limitations and Caveats

The sample size was relatively small (n=10) and the current study was not powered to adequately explore efficacy.

Results Point of Contact

Title
Yaminah Carter Research Coordinator
Organization
Temple University Episcopal Hospital
yaminah.carter@tuhs.temple.edu
2678097602

Study Officials

  • Kyle M. Kampman, M.D.

    U54 Principal Investigator - University of Pennsylvania

    PRINCIPAL INVESTIGATOR

  • Mary F. Morrison, M.D., M.S.

    Temple University

    PRINCIPAL INVESTIGATOR

  • M. I Walters, M.D.

    Temple University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 6, 2015

First Posted

September 30, 2015

Study Start

October 24, 2016

Primary Completion

May 25, 2018

Study Completion

May 25, 2018

Last Updated

November 3, 2023

Results First Posted

November 3, 2023

Record last verified: 2023-10

Locations

US(1)