Drug Interaction and Self Administration Studies of Compounds for Cocaine Use Disorder
Condition: Cocaine Use Disorder
Study type: Interventional
Phase: Phase 1

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).
    

Intervention name(s): Lorcaserin; Cocaine Intravenous (IV); Placebo comparator
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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
Other intervention name(s): Belviq
Intervention MeSH terms: Cocaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: Cocaine Use Disorder