Evaluating Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Transitioning From Buprenorphine Maintenance Prior to First Dose of VIVITROL

NCT02696434 | Completed Phase 3 Results

• 1 other identifier: ALK6428-A302
• Study Type: interventional
• Target: 101
• Locations: 1 country
• Sites: 9

Brief Summary

This study will evaluate the efficacy, safety, and tolerability of oral naltrexone used in conjunction with buprenorphine in adults with Opioid Use Disorder transitioning from buprenorphine maintenance prior to the first dose of VIVITROL.

Conditions

Opioid Use Disorder

Keywords

naltrexone; VIVITROL; buprenorphine; opioid; addiction

Outcome Measures

Primary Outcomes (1)

• Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection on Day 8

  Demonstrated by mild opioid withdrawal symptoms (Clinical Opiate Withdrawal Scale \[COWS\] \</=12 or Subjective Opiate Withdrawal Scale \[SOWS\] \</=10) following VIVITROL administration. The COWS is a clinician-rated questionnaire designed to measure 11 common opioid withdrawal signs or symptoms. The summed score provides information about the level of physical dependence on opioids. The range of COWS scores is 0-4 (none to minimal); 5-12 (mild); 13-24 (moderate); 25-36 (moderately severe); and 37-48 (severe withdrawal). The SOWS is a 16-item self-report questionnaire designed to measure the severity of opioid withdrawal symptoms. The subject rates the intensity of symptoms using a 5-point scale. The range of SOWS scores is 1-10 (mild); 11-20 (moderate); and 21-30 (severe).

  8 days

Secondary Outcomes (6)

• Proportion of Days With COWS Peak Score </=12 During the Treatment Period Prior to the VIVITROL Injection

  1 week

• Proportion of Post-VIVITROL Days (Days 9-11) in Which Subjects in Each Group Demonstrate Mild Opioid Withdrawal

  Days 9-11

• Mean Peak COWS Scores During the Treatment Period (Days 1/1a-7)

  Up to 7 days

• Area Under the Curve (AUC) for COWS Scores During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period

  The COWS was administered 4-6 times per day during the Treatment Period

• Mean Score for "Desire for Opioids" Visual Analog Scale (VAS) During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period

  Up to 11 days

Study Arms (2)

PBO NTX + BUP

ACTIVE COMPARATOR

Placebo naltrexone + buprenorphine

Drug: Placebo; Drug: Buprenorphine

NTX + BUP

EXPERIMENTAL

Naltrexone + buprenorphine

Drug: Naltrexone; Drug: Buprenorphine

Interventions

Naltrexone DRUG

daily dosing

NTX + BUP

Placebo DRUG

daily dosing

PBO NTX + BUP

Buprenorphine DRUG

daily dosing

NTX + BUP; PBO NTX + BUP

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Willing and able to provide informed consent
• Willing and able to provide government-issued identification
• Has a Body Mass Index (BMI) of 18.0-40.0 kg/m\^2
• Has a history of opioid use disorder diagnosis for at least 6 months
• Has a history of prescribed buprenorphine (or buprenorphine/naloxone) maintenance for the prior 3 or more consecutive months and is currently buprenorphine-maintained
• Must be voluntarily seeking treatment for opioid use disorder and be motivated to receive antagonist therapy
• Willing to abide by the contraception requirements for the duration of the study
• Additional criteria may apply

You may not qualify if:

• Is pregnant, planning to become pregnant or breastfeeding during the study
• Has a positive urine drug screen for opiates or oxycodone at screening
• Has used methadone within 30 days prior to study Day -5
• Has used naltrexone (oral or VIVITROL) within the 90 days prior to Day -5
• Has a condition, disease state, or previous medical history that would preclude safe participation in the study or affect the ability to adhere to the protocol visit schedule, requirements, or assessments
• Has a current diagnosis of schizoaffective disorder, bipolar disorder, or untreated and unstable major depressive disorder
• Is currently physiologically dependent on any psychoactive substance (except opioids, caffeine, or nicotine) requiring medical intervention for detoxification
• Has a history of hypersensitivity or adverse reaction to buprenorphine, naltrexone, VIVITROL, or naloxone
• Additional criteria may apply

Sponsors & Collaborators

• Alkermes, Inc.: lead

Study Sites (9)

Segal Institute for Clinical Research

Lauderhill, Florida, 33308, United States

Location

Research Centers of America, LLC

Oakland Park, Florida, 33334, United States

Location

Neuroscience Research Institute, Inc.

Winfield, Illinois, 60190, United States

Location

John Hopkins School of Medicine

Baltimore, Maryland, 21205-1911, United States

Location

Hassman Research Institute

Berlin, New Jersey, 08009, United States

Location

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

University of Pennsylvania Treatment Research Center

Philadelphia, Pennsylvania, 19104, United States

Location

Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (3)

• Mannelli P, Douaihy AB, Akerman SC, Legedza A, Fratantonio J, Zavod A, Sullivan MA. Characteristics and treatment preferences of individuals with opioid use disorder seeking to transition from buprenorphine to extended-release naltrexone in a residential setting. Am J Addict. 2022 Mar;31(2):142-147. doi: 10.1111/ajad.13264. Epub 2022 Feb 9.

  PMID: 35137481 DERIVED

• Mannelli P, Douaihy AB, Zavod A, Legedza A, Akerman SC, Sullivan MA. Patterns of withdrawal in patients with opioid use disorder (OUD) transitioning from untreated OUD or buprenorphine treatment to extended-release naltrexone. Am J Drug Alcohol Abuse. 2021 Nov 2;47(6):753-759. doi: 10.1080/00952990.2021.1969659. Epub 2021 Nov 9.

  PMID: 34752714 DERIVED

• Kosten T, Aharonovich E, Nangia N, Zavod A, Akerman SC, Lopez-Bresnahan M, Sullivan MA. Cognitive performance of patients with opioid use disorder transitioned to extended-release injectable naltrexone from buprenorphine: Post hoc analysis of exploratory results of a phase 3 randomized controlled trial. Addict Behav. 2020 Dec;111:106538. doi: 10.1016/j.addbeh.2020.106538. Epub 2020 Jul 3.

  PMID: 32777606 DERIVED

MeSH Terms

Conditions

Opioid-Related Disorders; Behavior, Addictive

Interventions

Naltrexone; Buprenorphine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Compulsive Behavior; Impulsive Behavior; Behavior

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Eva Stroynowski
• Organization: Alkermes

Eva.Stroynowski@alkermes.com

781-609-7000

Study Officials

• Maria A. Sullivan, MD, PhD

  Alkermes, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 26, 2016
• First Posted: March 2, 2016
• Study Start: April 1, 2016
• Primary Completion: November 1, 2017
• Study Completion: November 30, 2017
• Last Updated: February 12, 2019
• Results First Posted: February 12, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)