Trial Of NS2359 For The Treatment of Cocaine Dependence

NCT02798627 | Completed Phase 2 Results DMC

• 1 other identifier: 824109
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

Conditions

Cocaine Use Disorder

Outcome Measures

Primary Outcomes (1)

• The Number of Participants Who Achieved Abstinence From Cocaine During the Last Three Weeks of the Trial

  Number of Participants Who Report no Cocaine Use and Have no Cocaine Positive Urine Drug Screens in the NS2359 Group Versus the Placebo Group Comparator During the Last Three Weeks of the Trial \[ Time Frame: weeks 6,7.8 of the trial \] Number of subjects with cocaine abstinence as measured through three-times-weekly urine benzoylecgonine (BE) levels in urine drug screen (UDS) and self-reports of use from the Time Line Follow Back. UDS results and TLFB reports combined to yield weekly use/no-use indicators for each week of treatment.

  8 weeks

Secondary Outcomes (1)

• Average Weekly Cocaine Craving Scores NS2359 Group Versus the Placebo Group Comparator [ Time Frame: Once Per Week in Weeks 2 Through 8 ]

  8 weeks

Study Arms (2)

NS2359

EXPERIMENTAL

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

placebo

PLACEBO COMPARATOR

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

Interventions

NS2359 DRUG

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

NS2359

placebo DRUG

Placebo pills identical in appearance to the NS2359 will be provided

placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Pennsylvania: lead
• Saniona: collaborator
• The Dana Foundation: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Interventions

GSK372475

Limitations and Caveats

Small numbers of individuals analyzed. Some noncompliance per plasma NS2359 levels at mid and end treatment.

Results Point of Contact

• Title: Kyle Kampman, MD
• Organization: University of Pennsylvania Perelman School of Medicine

kampman@pennemdicine.upenn.edu

2157462764

Study Officials

• Wade Berrettini, MD, PhD

  University of Pennsylvania Perelman School of Medicine, Department of Psychiatry

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry

Study Record Dates

• First Submitted: May 17, 2016
• First Posted: June 14, 2016
• Study Start: May 1, 2016
• Primary Completion: March 1, 2020
• Study Completion: October 1, 2020
• Last Updated: May 24, 2021
• Results First Posted: May 24, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)