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

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.