Trial Of NS2359 For The Treatment of Cocaine Dependence

NCT ID: NCT02798627

Last Updated: 2021-05-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-05-31
• Study Completion Date: 2020-10-31

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.

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).

Conditions

Cocaine Use Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

NS2359

Intervention Type: DRUG

NS2359 is a small molecule which inhibits the reuptake of dopamine, norepinephrine and serotonin with equal affinity.

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.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Placebo pills identical in appearance to the NS2359 will be provided

Interventions

NS2359

NS2359 is a small molecule which inhibits the reuptake of dopamine, norepinephrine and serotonin with equal affinity.

Intervention Type: DRUG

placebo

Placebo pills identical in appearance to the NS2359 will be provided

Intervention Type: DRUG

Eligibility 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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• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Saniona

INDUSTRY

Sponsor Role: collaborator

The Dana Foundation

OTHER

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Kyle Kampman

Professor of Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Wade Berrettini, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania Perelman School of Medicine, Department of Psychiatry

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

824109

Identifier Type: -

Identifier Source: org_study_id