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Trial Of NS2359 For The Treatment of Cocaine Dependence

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ClinicalTrials.gov Identifier: NCT02798627
Recruitment Status : Recruiting
First Posted : June 14, 2016
Last Update Posted : September 12, 2019
Sponsor:
Collaborators:
Saniona
The Dana Foundation
Information provided by (Responsible Party):
Kyle Kampman, University of Pennsylvania

Brief 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.

Condition or disease Intervention/treatment Phase
Cocaine Use Disorder Drug: NS2359 Drug: placebo Phase 2

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).


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Double-Blind, Placebo-Controlled, Trial Of NS2359 For The Treatment of Cocaine Dependence
Study Start Date : May 2016
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: NS2359
The initial dose of the NS2359 will be two mg once daily. Patients with difficult adverse events at the 2 mg dose will be allowed to reduce to 1 mg once daily. Subjects will participate in weekly cognitive behavioral relapse prevention psychotherapy from week 2 through week 9.
Drug: NS2359
NS2359 is a small molecule which inhibits the reuptake of dopamine, norepinephrine and serotonin with equal affinity.

Placebo Comparator: placebo
Placebo pills matched to NS2359 pills will be given once daily. Patients with difficult adverse events at the 2 mg placebo will be allowed to reduce to 1 mg placebo once daily. Subjects will participate in weekly cognitive behavioral relapse prevention psychotherapy from week 2 through week 9.
Drug: placebo
Placebo pills identical in appearance to the NS2359 will be provided




Primary Outcome Measures :
  1. Trial Of NS2359 For The Treatment of Cocaine Dependence: urine drug screen for benzoylecgonine [ Time Frame: 8 weeks ]
    Urine samples will be provided by each participant every Monday, Wednesday and Friday for weeks 2-9. These urine samples will be assayed for benzoylecgonine, a cocaine metabolite. If a urine sample tests positive for BE during a week, that week will be reported as a cocaine use week. If all 3 samples test negative for BE, that week will be reported as an abstinent week.


Secondary Outcome Measures :
  1. Trial Of NS2359 For The Treatment of Cocaine Dependence: alcohol intake assessment [ Time Frame: 8 weeks ]
    Alcohol intake will be assessed by asking each participant at each clinic visit to specify the number of alcohol drinks consumed each day since the most recent clinic visit. The number of drinks/day and the number of drinking days will be reported for each week for each participant.

  2. Trial Of NS2359 For The Treatment of Cocaine Dependence: tobacco use assessment [ Time Frame: 8 weeks ]
    Cigarettes smoked per day will be recorded for each participant at baseline and at weeks 5 and week 9, the end of the medication phase.

  3. Trial Of NS2359 For The Treatment of Cocaine Dependence: Treatment emergent adverse event assessment [ Time Frame: 8 weeks ]
    Participants will be asked about adverse events at each clinic visit. Expected adverse events include insomnia, anxiety, dizziness, dry mouth, tiredness. Adverse events will be reported as summary data across all participants for each adverse event, including estimates of severity and frequency.



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  1. 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.
  2. Needs treatment with any psychoactive medications (with the exception of diphenhydramine or melatonin, if necessary, for sleep).
  3. Meets current or lifetime DSM-V criteria for schizophrenia or any psychotic disorder, or organic mental disorder.
  4. 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.
  5. Has evidence of a history of significant hematological, pulmonary, endocrine, cardiovascular, renal or gastrointestinal disease.
  6. Use of an investigational medication in the 30 days prior to randomization.
  7. 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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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02798627


Locations
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United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Kyle Kampman, MD    215-222-3200 ext 109    kampman@mail.med.upenn.edu   
Contact: Wade Berrettini, MD, PhD    2158980092    wadeb@mail.med.upenn.edu   
Sponsors and Collaborators
University of Pennsylvania
Saniona
The Dana Foundation
Investigators
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Principal Investigator: Wade Berrettini, MD, PhD University of Pennsylvania Perelman School of Medicine, Department of Psychiatry

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Responsible Party: Kyle Kampman, Professor of Psychiatry, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02798627     History of Changes
Other Study ID Numbers: 824109
First Posted: June 14, 2016    Key Record Dates
Last Update Posted: September 12, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Cocaine-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Cocaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents