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

Phase 3

Completed

• Conditions: Opioid Use Disorder
• Interventions: Drug: Placebo; Drug: Naltrexone; Drug: Buprenorphine

• Registration Number: NCT02696434
• Lead Sponsor: Alkermes, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-02-26
• Study First Submitted QC: 2016-02-26
• Study First Posted: 2016-03-02
• Study Start: 2016-04
• Primary Completion: 2017-11
• Study Completion: 2017-11-30
• Results First Submitted: 2018-10-31
• Status Verified: 2019-01
• Results First Submitted QC: 2019-01-18
• Last Update Submitted: 2019-01-18
• Results First Posted: 2019-02-12
• Last Update Posted: 2019-02-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 101

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PBO NTX + BUP	Placebo	Placebo naltrexone + buprenorphine
PBO NTX + BUP	Buprenorphine	Placebo naltrexone + buprenorphine
NTX + BUP	Naltrexone	Naltrexone + buprenorphine
NTX + BUP	Buprenorphine	Naltrexone + buprenorphine

Primary Outcome Measures

Name	Time	Method
Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection on Day 8	8 days	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

Name	Time	Method
Incidence of Adverse Events (AEs)	Up to 42 days	Number and percentage of subjects who experienced AEs.
Proportion of Post-VIVITROL Days (Days 9-11) in Which Subjects in Each Group Demonstrate Mild Opioid Withdrawal	Days 9-11	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)	Up to 7 days	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 Days With COWS Peak Score </=12 During the Treatment Period Prior to the VIVITROL Injection	1 week	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 COWS was administered 4-6 times per day during the Treatment 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	Up to 11 days	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."

Trial Locations

Locations (9)

John Hopkins School of Medicine; 🇺🇸 Baltimore, Maryland, United States

Neuroscience Research Institute, Inc.; 🇺🇸 Winfield, Illinois, United States

Segal Institute for Clinical Research; 🇺🇸 Lauderhill, Florida, United States

Research Centers of America, LLC; 🇺🇸 Oakland Park, Florida, United States

New York State Psychiatric Institute; 🇺🇸 New York, New York, United States

Hassman Research Institute; 🇺🇸 Berlin, New Jersey, United States

University of Pennsylvania Treatment Research Center; 🇺🇸 Philadelphia, Pennsylvania, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Western Psychiatric Institute and Clinic of University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States