Trial Of NS2359 For The Treatment of Cocaine Dependence

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).

Inclusion criteria

• Male and females, 18-65 years old.
• Meets diagnostic criteria (DSM-V) for current diagnosis of cocaine use disorder, moderate to severe, by semi-structured interview.
• In the past 30 days, used no less than $100-worth of cocaine
• Speaks, understands, and prints in English.

Exclusion criteria

• Meets DSM-V criteria for substance use disorder, moderate to severe, for a substance other than cocaine, alcohol or nicotine. Subjects with comorbid alcohol use disorder will be accepted if their alcohol use disorder is not severe enough to require a medical alcohol detoxification.
• Needs treatment with any psychoactive medications (with the exception of diphenhydramine or melatonin, if necessary, for sleep).
• Meets current or lifetime DSM-V criteria for schizophrenia or any psychotic disorder, or organic mental disorder.
• Has another Axis I psychiatric disorder that in the opinion of the physician will interfere with completion of the study or place the patient at heightened risk through participation in the trial.
• Has evidence of a history of significant hematological, pulmonary, endocrine, cardiovascular, renal or gastrointestinal disease.
• Use of an investigational medication in the 30 days prior to randomization.
• Is female and has a positive pregnancy test, is contemplating pregnancy in the next 6 months, is nursing, or is not using effective contraception (if relevant).

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