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Drug Interaction and Self Administration Studies of Compounds for Cocaine Use Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02537873
Recruitment Status : Completed
First Posted : September 2, 2015
Results First Posted : May 12, 2020
Last Update Posted : May 12, 2020
Sponsor:
Collaborator:
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Virginia Commonwealth University

Brief Summary:
The overall goal of this project is to develop initial human data on effects of novel compounds on safety (interactions with cocaine) and efficacy (subjective response to cocaine and self administration data) in non-treatment seeking cocaine use disorder subjects. The compound to be studied will be the 5-HT2CR agonist lorcaserin. Lorcaserin and other 5-HT2CR agonists have been shown to reduce cocaine self-administration and cue reactivity in rodents. In addition there is human safety data in non-cocaine using subjects for lorcaserin as it is currently FDA approved for obesity, and safety data from a cocaine interaction study in rodents , but there is no human cocaine interaction/PK data and no PD data to support potential dosages for phase II clinical trials.

Condition or disease Intervention/treatment Phase
Cocaine Use Disorder Drug: Lorcaserin Drug: Cocaine Intravenous (IV) Drug: Placebo comparator Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Official Title: Phase I Drug Interaction and Self Administration Studies of Compounds for Cocaine Use Disorder
Study Start Date : July 2015
Actual Primary Completion Date : July 19, 2018
Actual Study Completion Date : July 19, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Drug Reactions

Arm Intervention/treatment
Experimental: Arm 1: Lorcaserin and Cocaine IV

Lorcaserin 10 mg administered orally once daily for 6 days then increasing to twice daily for 3 days.

Cocaine IV (intravenous) administered in ascending doses of 0, 10, 20, 40 mg on study days 1, 2, 6 and 12.

Drug: Lorcaserin
Lorcaserin HCL 10mg tablets (Belviq, Arena Pharmaceuticals)
Other Name: Belviq

Drug: Cocaine Intravenous (IV)
Cocaine IV administered at doses of 10, 20 and 40 mg during 4 dosing sessions

Placebo Comparator: Arm 2: Placebo Comparator and Cocaine IV
Dextrose placebo in gelatin capsule identical to experimental drug. Cocaine IV (intravenous) administered in ascending doses of 0, 10, 20, 40 mg on study days 1, 2, 6 and 12.
Drug: Cocaine Intravenous (IV)
Cocaine IV administered at doses of 10, 20 and 40 mg during 4 dosing sessions

Drug: Placebo comparator
Dextrose in gelatin capsule




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) - Heart Rate [ Time Frame: Baseline to up to 5 hours on up to day 12 of the study ]
    Change in Heart rate (HR) measures during saline infusions will be compared to HR and BP after each cocaine infusion.

  2. Cocaine Self-administration Choice Selection [ Time Frame: 13 days ]
    During a study visit 13 days after participant enrollment, participants will be allowed to choose to receive an infusion of cocaine or $5. Number of times participants self-administered Cocaine over an approximately 2 1/2 hour period in the morning and in the afternoon will be counted.

  3. Change in Subjective Experience [ Time Frame: Day 12, pre-infusion to post-infusion (up to 5 hours) ]
    During a study visit, participants will be given an infusion of cocaine. Participants will rate their subjective craving for cocaine on a visual analog scale. The scale is rated from Not at all to Extremely. Scores are calculated by measuring in centimeters from Not at all (0) to where the participant marked with the highest score being 100. Participants will rate their subjective experience at baseline (prior to drug infusion) and after cocaine infusion.

  4. Cocaine PK With Placebo [ Time Frame: 2 days ]
    Regardless of randomization category, all participants will receive the placebo on days 1 and 2 in a single blind fashion. Plasma concentration-time profiles of cocaine after cocaine infusion during placebo administration (Day 2) will be analyzed to determine how many participant's pharmacokinetic (PK) parameter estimates after using cocaine differ from expected PK parameter estimates for a typical individual using cocaine.

  5. Cocaine PK With Study Drug [ Time Frame: Day 12 ]
    Plasma concentration-time profiles of cocaine after cocaine infusion during study drug (Lorcaserin or placebo) administration (Day 12) will be analyzed to determine how many participant's pharmacokinetic (PK) parameter estimates after using cocaine differ from expected PK parameter estimates for a typical individual using cocaine.

  6. Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) - Change in Blood Pressure [ Time Frame: Day 12, baseline to final cocaine infusion (approximately 5 hours) ]
    Change in blood pressure (BP) measures during saline infusions will be compared to HR and BP after each cocaine infusion.


Secondary Outcome Measures :
  1. Response Inhibition During Immediate Memory Task (IMT) [ Time Frame: 3 days (Study days 1, 8, 11) ]
    Commission errors on the IMT (Immediate Memory Task) will be compared between lorcaserin and placebo subjects to determine the extent to which this measure is modified by the administration of lorcaserin using repeated measures ANOVA.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 59 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

In order to participate in this study, subjects must:

  1. Males and females between 18 and 59 years-of-age.
  2. Understand the study procedures and provide written informed consent.
  3. Meet current DSM-5 criteria for cocaine use disorder, at least moderate severity, and current DSM-IV diagnosis of cocaine dependence, but are not seeking treatment.
  4. Currently using cocaine by smoking or intravenous route of administration as determined by self-report and have a positive urine drug screen for cocaine during screening.
  5. Have vital signs as follows: resting pulse below 95 bpm, blood pressures below 140 mm Hg systolic and 90 mm Hg diastolic.
  6. Have no clinically significant abnormalities in the judgment of the study physician in hematology and chemistry laboratory tests including liver function tests.
  7. Have sinus rhythm with normal conduction (including QTcF less than 440 ms) by ECG.
  8. Have no contraindications for study participation as determined by medical history and physical examination.
  9. Be able to demonstrate an understanding of study procedures and follow instructions including behavioral laboratory testing.
  10. No pregnant or nursing women will be permitted in the study, and women must either be unable to conceive (i.e., surgically sterilized, sterile, or postmenopausal) or be using a reliable form of contraception (e.g., abstinence, birth control pills, intrauterine device with spermicide, or condoms). Men will be advised to use condoms. All females must provide negative pregnancy urine tests before study entry, at each visit during the study, and at the end of study participation.
  11. Have hemoglobin/hematocrit values within normal limits based on age and gender.

In order to participate in the study, subjects must not:

  1. Meet current DSM-5 diagnosis of any psychoactive substance use disorder other than cocaine, opiates, marijuana, or nicotine. Diagnosis of mild to moderate use disorder for alcohol will not be considered exclusionary.
  2. Have a DSM-5 axis I psychiatric disorder other than substance use disorder including but not limited to Bipolar Disorder, Major Depressive Disorder, ADHD, or Schizophrenia or a neurological disorder requiring ongoing treatment and/or making study participation unsafe.
  3. Have any previous medically adverse reaction to cocaine, including loss of consciousness, chest pain, or epileptic seizure.
  4. Have any clinically significant medical disorder including cardiovascular (including hypertension), pulmonary, CNS, hepatic, or renal disorder.
  5. Have a history of seizures (excluding childhood febrile seizures), or loss of consciousness for more than 20 minutes.
  6. Have significant current suicidal or homicidal ideation or a history of suicide attempt within the past 6 months.
  7. Have conditions of probation or parole requiring reports of drug use to officers of the court.
  8. Have impending incarceration.
  9. Have a positive HIV test by self-report or history.
  10. Be pregnant or nursing or not using a reliable form of contraception if able to conceive. All females must provide negative pregnancy urine tests at screening, and daily after hospital admission.
  11. Have any other illness, or condition, which in the opinion of the PI would preclude safe and/or successful completion of the study.
  12. Have a positive breath alcohol test or urine drug screening positive for drugs of abuse with the exception of cocaine, opiates, cocaine metabolites, and marijuana.
  13. Have a score greater than 5 on the Clinical Opiates Withdrawal Scale (COWS) on any screening, monitoring or hospital study visit.
  14. Subjects who are allergic to lorcaserin.
  15. Subjects who have taken any investigational drug within 90 days prior to baseline.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02537873


Locations
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United States, Virginia
Virginia Commonwealth University, Institute for Drug and Alcohol Studies
Richmond, Virginia, United States, 23219
Sponsors and Collaborators
Virginia Commonwealth University
National Institute on Drug Abuse (NIDA)
Investigators
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Principal Investigator: Frederick G Moeller, MD Virginia Commonwealth University
  Study Documents (Full-Text)

Documents provided by Virginia Commonwealth University:
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Responsible Party: Virginia Commonwealth University
ClinicalTrials.gov Identifier: NCT02537873    
Other Study ID Numbers: HM20003768
1U54DA038999 ( U.S. NIH Grant/Contract )
First Posted: September 2, 2015    Key Record Dates
Results First Posted: May 12, 2020
Last Update Posted: May 12, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Virginia Commonwealth University:
Cocaine Use Disorder
Additional relevant MeSH terms:
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Disease
Pathologic Processes
Cocaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents