Trial Of NS2359 For The Treatment of Cocaine Dependence
Condition: Cocaine Use Disorder
MeSH terms: Cocaine-Related Disorders
Study type: Interventional
Phase: Phase 2

Summary: 
      NS2359 attenuates the euphoria associated with cocaine use. In a manner parallel to cocaine,
      NS2359 blocks the reuptake of dopamine (DA), norepinephrine (NE), and serotonin (5HT) with
      nanomolar affinities at the 3 transporters. In primates NS2359 significantly attenuated
      cocaine self-administration. In several phase II clinical trials for major depressive
      disorder and adult attention deficit disorder, NS2359 did not cause euphoria. NS2359
      exhibited no abuse potential in a human laboratory study comparing NS2359 with amphetamine.
      In a phase I human laboratory interaction study, NS2359 showed no toxicity after 20 or 40 mg
      of cocaine, but it attenuated the both the rewarding and cardiovascular effects of
      intravenous cocaine. On the basis of these promising studies, investigators propose a Phase
      II double-blind clinical trial of NS2359 in cocaine addiction (CA). The proposed trial will
      involve 100 CA subjects participating in an eight week trial, including a 1-week baseline and
      8 weeks of NS2359 or placebo treatment. Four weeks after completing the medication phase,
      there will be one follow-up visit. Subjects will be randomly assigned to treatment with
      placebo or 2 mg NS2359 daily, with a possible decrease to 1 mg daily for adverse events. This
      dose range is selected on the basis of phase I and II evidence of tolerability and NS2359
      plasma levels which were associated with blockade of cocaine reward. This project has the
      potential to identify the first effective pharmacotherapy for CA.
    

Detailed description: 
      In this phase II randomized double-blind, placebo-controlled trial, 40 persons will be
      randomized to NS2359 and 40 to placebo. The primary hypothesis is: more NS2359-treated
      subjects (compared to placebo-treated subjects) will achieve 3 consecutive weeks of cocaine
      abstinence, as measured by urine benzoylecgonine (BE) assay, during the last three weeks of
      the trial. The study is 9 weeks: one week of screening, followed by an 8-week double-blind,
      placebo-controlled trial. All subjects will receive weekly cognitive behavioral therapy (CBT)
      to encourage abstinence during their 3 times weekly clinic visits. Investigators expect ~ 20%
      dropout rate, based on our recent CA clinical trials (eg, Kampman et al, 2015 and 2013), so
      80 randomized patients will yield ~ 64 study completers. There will be a 1 month start-up
      period, followed by 20 months of recruitment for the study. The 1 month start-up period will
      allow for training of staff, preparation of study capsules, placement of study
      advertisements, etc. Penn IRB approval has been obtained. There will be a 2-month termination
      period to allow the final patients to complete the study. Data cleaning, statistical analyses
      and preparation of reports will be done in the final two months. Based on recent cocaine
      pharmacotherapy trials conducted by our team, monthly enrollment of ~4 CA participants
      (respondents to flyers and advertisements) is feasible.

      Recruitment will occur at the University of Pennsylvania's Treatment Research Center (TRC),
      led by Kyle Kampman, MD, and Wade Berrettini, MD, PhD, Professors of Psychiatry at Penn. At
      the TRC, CA patients are respondents to advertisements for free treatment of CA. The
      ethnicity is 90% African-American, 9 % European-American, 70% male, mean age 47 (+/- 12).
    

Intervention name(s): NS2359; placebo
Intervention type(s): Drug; Drug
Intervention description(s): NS2359 is a small molecule which inhibits the reuptake of dopamine, norepinephrine and serotonin with equal affinity.; Placebo pills identical in appearance to the NS2359 will be provided
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment