Drug Interaction and Self Administration Studies of Compounds for Cocaine Use Disorder
Condition: Cocaine Use Disorder
Intervention: Lorcaserin; Cocaine Intravenous (IV); Placebo comparator
Intervention description: Lorcaserin HCL 10mg tablets (Belviq, Arena Pharmaceuticals); Cocaine IV administered at doses of 10, 20 and 40 mg during 4 dosing sessions; Dextrose in gelatin capsule
Intervention MeSH terms: Cocaine
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Maximum age: 59 Years
Healthy volunteers: No
Keywords: Cocaine Use Disorder

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.
    

Eligibility 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.