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

Primary Purpose

Opioid Use Disorder

Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Naltrexone
Placebo
Buprenorphine
Sponsored by
Alkermes, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Opioid Use Disorder focused on measuring naltrexone, VIVITROL, buprenorphine, opioid, addiction

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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 history of seizures or has received anticonvulsant therapy within the past 5 years for treatment of seizures (use of anticonvulsant during the past detoxification is not exclusionary)
  • 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

Sites / Locations

  • Segal Institute for Clinical Research
  • Research Centers of America, LLC
  • Neuroscience Research Institute, Inc.
  • John Hopkins School of Medicine
  • Hassman Research Institute
  • New York State Psychiatric Institute
  • Duke University Medical Center
  • University of Pennsylvania Treatment Research Center
  • Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

PBO NTX + BUP

NTX + BUP

Arm Description

Placebo naltrexone + buprenorphine

Naltrexone + buprenorphine

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

Proportion of Days With COWS Peak Score </=12 During the Treatment Period Prior to the VIVITROL Injection
The Clinical Opiate Withdrawal Scale (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).
Proportion of Post-VIVITROL Days (Days 9-11) in Which Subjects in Each Group Demonstrate Mild Opioid Withdrawal
COWS score </=12; The Clinical Opiate Withdrawal Scale (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).
Mean Peak COWS Scores During the Treatment Period (Days 1/1a-7)
The Clinical Opiate Withdrawal Scale (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).
Area Under the Curve (AUC) for COWS Scores During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period
The Clinical Opiate Withdrawal Scale (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 daily AUC COWS score is derived based on the actual time (unit in minutes) COWS administered on each day by using the linear trapezoidal rule, and then divided by the COWS administration duration (last COWS administration time minus first COWS administration time) for that day. The normalized AUC COWS score is the summation of daily AUC COWS score during the relevant period divided by the number of days with daily AUC COWS score.
Mean Score for "Desire for Opioids" Visual Analog Scale (VAS) During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period
The Desire for Opioids VAS uses a 100-mm, horizontal linear scale, with 0 anchored on the left representing "no desire for opioids" and 100 anchored on the right representing "strongest imaginable desire for opioids."
Incidence of Adverse Events (AEs)
Number and percentage of subjects who experienced AEs.

Full Information

First Posted
February 26, 2016
Last Updated
January 18, 2019
Sponsor
Alkermes, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02696434
Brief Title
Evaluating Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Transitioning From Buprenorphine Maintenance Prior to First Dose of VIVITROL
Official Title
A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Safety, Tolerability, and Efficacy of Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Transitioning From Buprenorphine Maintenance Prior to First Dose of VIVITROL
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
April 2016 (undefined)
Primary Completion Date
November 2017 (Actual)
Study Completion Date
November 30, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Alkermes, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid Use Disorder
Keywords
naltrexone, VIVITROL, buprenorphine, opioid, addiction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
101 (Actual)

8. Arms, Groups, and Interventions

Arm Title
PBO NTX + BUP
Arm Type
Active Comparator
Arm Description
Placebo naltrexone + buprenorphine
Arm Title
NTX + BUP
Arm Type
Experimental
Arm Description
Naltrexone + buprenorphine
Intervention Type
Drug
Intervention Name(s)
Naltrexone
Intervention Description
daily dosing
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
daily dosing
Intervention Type
Drug
Intervention Name(s)
Buprenorphine
Intervention Description
daily dosing
Primary Outcome Measure Information:
Title
Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection on Day 8
Description
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).
Time Frame
8 days
Secondary Outcome Measure Information:
Title
Proportion of Days With COWS Peak Score </=12 During the Treatment Period Prior to the VIVITROL Injection
Description
The Clinical Opiate Withdrawal Scale (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).
Time Frame
1 week
Title
Proportion of Post-VIVITROL Days (Days 9-11) in Which Subjects in Each Group Demonstrate Mild Opioid Withdrawal
Description
COWS score </=12; The Clinical Opiate Withdrawal Scale (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).
Time Frame
Days 9-11
Title
Mean Peak COWS Scores During the Treatment Period (Days 1/1a-7)
Description
The Clinical Opiate Withdrawal Scale (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).
Time Frame
Up to 7 days
Title
Area Under the Curve (AUC) for COWS Scores During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period
Description
The Clinical Opiate Withdrawal Scale (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 daily AUC COWS score is derived based on the actual time (unit in minutes) COWS administered on each day by using the linear trapezoidal rule, and then divided by the COWS administration duration (last COWS administration time minus first COWS administration time) for that day. The normalized AUC COWS score is the summation of daily AUC COWS score during the relevant period divided by the number of days with daily AUC COWS score.
Time Frame
The COWS was administered 4-6 times per day during the Treatment Period
Title
Mean Score for "Desire for Opioids" Visual Analog Scale (VAS) During the Treatment Period and VIVITROL Induction and Post-VIVITROL Observation Period
Description
The Desire for Opioids VAS uses a 100-mm, horizontal linear scale, with 0 anchored on the left representing "no desire for opioids" and 100 anchored on the right representing "strongest imaginable desire for opioids."
Time Frame
Up to 11 days
Title
Incidence of Adverse Events (AEs)
Description
Number and percentage of subjects who experienced AEs.
Time Frame
Up to 42 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 history of seizures or has received anticonvulsant therapy within the past 5 years for treatment of seizures (use of anticonvulsant during the past detoxification is not exclusionary) 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Maria A. Sullivan, MD, PhD
Organizational Affiliation
Alkermes, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Segal Institute for Clinical Research
City
Lauderhill
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
Facility Name
Research Centers of America, LLC
City
Oakland Park
State/Province
Florida
ZIP/Postal Code
33334
Country
United States
Facility Name
Neuroscience Research Institute, Inc.
City
Winfield
State/Province
Illinois
ZIP/Postal Code
60190
Country
United States
Facility Name
John Hopkins School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205-1911
Country
United States
Facility Name
Hassman Research Institute
City
Berlin
State/Province
New Jersey
ZIP/Postal Code
08009
Country
United States
Facility Name
New York State Psychiatric Institute
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
University of Pennsylvania Treatment Research Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35137481
Citation
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.
Results Reference
derived
PubMed Identifier
34752714
Citation
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.
Results Reference
derived
PubMed Identifier
32777606
Citation
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.
Results Reference
derived

Learn more about this trial

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

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