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

NCT02537873 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: HM200037681U54DA038999
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Cocaine Use Disorder

Keywords

Cocaine Use Disorder

Outcome Measures

Primary Outcomes (6)

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) - Heart Rate

  Change in Heart rate (HR) measures during saline infusions will be compared to HR and BP after each cocaine infusion.

  Baseline to up to 5 hours on up to day 12 of the study

• Cocaine Self-administration Choice Selection

  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.

  13 days

• Change in Subjective Experience

  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.

  Day 12, pre-infusion to post-infusion (up to 5 hours)

• Cocaine PK With Placebo

  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.

  2 days

• Cocaine PK With Study Drug

  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.

  Day 12

• Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) - Change in Blood Pressure

  Change in blood pressure (BP) measures during saline infusions will be compared to HR and BP after each cocaine infusion.

  Day 12, baseline to final cocaine infusion (approximately 5 hours)

Secondary Outcomes (1)

• Response Inhibition During Immediate Memory Task (IMT)

  3 days (Study days 1, 8, 11)

Study Arms (2)

Arm 1: Lorcaserin and Cocaine IV

EXPERIMENTAL

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; Drug: Cocaine Intravenous (IV)

Arm 2: Placebo Comparator and Cocaine IV

PLACEBO COMPARATOR

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); Drug: Placebo comparator

Interventions

Lorcaserin DRUG

Lorcaserin HCL 10mg tablets (Belviq, Arena Pharmaceuticals)

Also known as: Belviq

Arm 1: Lorcaserin and Cocaine IV

Cocaine Intravenous (IV) DRUG

Cocaine IV administered at doses of 10, 20 and 40 mg during 4 dosing sessions

Arm 1: Lorcaserin and Cocaine IV; Arm 2: Placebo Comparator and Cocaine IV

Placebo comparator DRUG

Dextrose in gelatin capsule

Arm 2: Placebo Comparator and Cocaine IV

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Virginia Commonwealth University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Virginia Commonwealth University, Institute for Drug and Alcohol Studies

Richmond, Virginia, 23219, United States

Location

MeSH Terms

Interventions

lorcaserin

Results Point of Contact

• Title: F. Gerard Moeller, M.D.
• Organization: Virginia Commonwealth University

lmbobb@vcu.edu

804-628-7788

Study Officials

• Frederick G Moeller, MD

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2015
• First Posted: September 2, 2015
• Study Start: July 1, 2015
• Primary Completion: July 19, 2018
• Study Completion: July 19, 2018
• Last Updated: May 12, 2020
• Results First Posted: May 12, 2020

Record last verified: 2020-05

Locations

US (1)