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

NCT ID: NCT02537873

Last Updated: 2020-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2018-07-19

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.

Detailed Description

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. This project will provide innovative data on effects of novel compounds on cocaine self-administration in addition to needed safety data on drug interactions with cocaine. This is a Phase I human drug interaction study examining the safety of concurrent administration of cocaine with novel compounds, and the effects of the novel compounds on subjective response to cocaine and cocaine self-administration in non-treatment seeking cocaine use disorder subjects. This data will provide important information for go/no-go decisions on phase II clinical trials using medications as a tool to enhance abstinence. The initial compound to be studied will be the 5-HT2CR agonist lorcaserin, which has 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, but there is no human cocaine interaction/PK data and no PD data to support potential dosages for phase II clinical trials.

This is a single center, double-blind, placebo-controlled, randomized, 1b/2a study. 18 of subjects are planned. Each subject will be administered a single dose of study drug three times, one week apart, consisting each time of various doses of active or placebo. Each subject will receive three of the four experimental treatments. Subjects will be assigned to the treatments in random order. Evaluations will be taken at baseline and 4 hours at each of the 3 study visits.

Screening data will be reviewed to determine subject eligibility. Subjects who meet all inclusion criteria and none of the exclusion criteria will be entered into the study. If subjects meet inclusion criteria, they will be admitted as hospital inpatients during the 14 study days to prevent drug and alcohol use and maintain complete monitoring for adverse events.

The following treatment regimens will be used:

Lorcaserin will be 10mg once daily increasing to 10mg twice daily. Placebo or Comparator - identical placebo capsules administered at the same time as lorcaserin.

Total duration of subject participation including eligibility screening (Study days -3 - 0), on-unit study days (Study days 1-14), and follow-up visits (Study days 16 and 20) will be three weeks. Total duration of the study is expected to be 18 months.

Detailed description of the in-hospital portion of study (Study days 1-14) is as follows:

After a screening cocaine infusion to determine safety, eligible subjects will be randomized to Group A -placebo only or Group B -placebo followed by an ascending dose of lorcaserin. Six subjects will be assigned to Group A (placebo) and 12 subjects will be assigned to Group B (active lorcaserin).

1. Days 1-2: All subjects will receive placebo on days 1-2 in a single blind fashion. Vital signs including heart rate, blood pressure and respiration rate will be obtained 15 minutes before and 15, 30 and 60 minutes after placebo administration. Days 1-2 will be single-blind placebo, whereas all remaining study days will be double-blind.

2. Days 3-9: On days 3-9, subject group A will receive one placebo pill twice daily, and group B will receive one placebo pill in the morning and one matching lorcaserin 10 mg pill in the evening, for a total dose of 10 mg daily. ECG with QTc will be performed daily. If the QTc is prolonged greater than 30ms over baseline lorcaserin dosage will be held.

3. Days 10-12: subjects in group B will have a blinded dosage increase to 10 mg of lorcaserin twice daily. Vital signs including heart rate, blood pressure and respiration rate will be obtained 15 minutes before and 15, 30 and 60 minutes after placebo/lorcaserin administration. ECG with QTc will be performed daily under the supervision of a study physician. If the QTc is prolonged greater than 30ms over baseline lorcaserin dosage will be held.

4. Day 13 subjects in group B will be administered 10mg of lorcaserin in the morning only, and subjects in group A will be administered matching placebo in the morning. Subjects will be discharged on day 14.

5. Cocaine Infusion Sessions (Days 1, 2, 6, and 12): All subjects will undergo an ascending dose intravenous cocaine administration after admission on day 1 to ensure safety of later cocaine studies.

To assess the safety and subjective effects of cocaine in the presence of lorcaserin, subjects will receive ascending doses of intravenous cocaine (10 mg, 20 mg, 40 mg), with each cocaine administration separated by one hour. In addition, 0 mg cocaine (saline) infusion will be randomly given after the first dose of cocaine in order to aid in blinding investigators and subjects to the order of drug administration. Infusions will be carried out at 9:00am, 10:00am, 11:00am and 12:00pm (Day 1), or at 1:00 p.m., 2:00 p.m., 3:00 p.m., and 4:00 p.m. (Days 2, 6, and 12).

Conditions

Cocaine Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Lorcaserin

Intervention Type: DRUG

Lorcaserin HCL 10mg tablets (Belviq, Arena Pharmaceuticals)

Cocaine Intravenous (IV)

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Cocaine Intravenous (IV)

Intervention Type: DRUG

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

Placebo comparator

Intervention Type: DRUG

Dextrose in gelatin capsule

Interventions

Lorcaserin

Lorcaserin HCL 10mg tablets (Belviq, Arena Pharmaceuticals)

Intervention Type: DRUG

Cocaine Intravenous (IV)

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

Intervention Type: DRUG

Placebo comparator

Dextrose in gelatin capsule

Intervention Type: DRUG

Other Intervention Names

Belviq

Eligibility Criteria

Exclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 59 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frederick G Moeller, MD

Role: PRINCIPAL_INVESTIGATOR

Virginia Commonwealth University

Locations

Virginia Commonwealth University, Institute for Drug and Alcohol Studies

Richmond, Virginia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1U54DA038999

Identifier Type: NIH

Identifier Source: secondary_id

View Link

HM20003768

Identifier Type: -

Identifier Source: org_study_id