Back to resultsNaltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Prior to First Dose of VIVITROL® (Naltrexone for Extended-Release Injectable Suspension)
Primary Purpose
Opioid Use Disorder
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
NTX/BUP
NTX/PBO-B
PBO-N/PBO-B
Sponsored by
About this trial
This is an interventional treatment trial for Opioid Use Disorder focused on measuring Alkermes, Buprenorphine, Naltrexone, Vivitrol, Opioid Use, Opiates, Dependence, Abuse, Heroin, Painkillers, Substance Abuse
Eligibility Criteria
Inclusion Criteria:
- Willing and able to provide informed consent
- Willing and able to provide government-issued identification
- Has a BMI of 18.0-40.0 kg/m^2
- Has a physiologic dependence on opioids
- Is voluntarily seeking treatment for opioid use disorder and willing to completely withdraw from his/her opioid use throughout the study with desire for or motivation for antagonist therapy
- Wiling 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 used Buprenorphine within 7 days prior to randomization
- Has used Methadone within 14 days prior to randomization
- Has a history of VIVITROL use within 90 days prior to screening or has used oral naltrexone within 14 days prior to randomization
- Has a history of seizures or has received anticonvulsant therapy within the past 5 years
- 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, or Naloxone
- Has a history of more than 3 unsuccessful inpatient or medically assisted outpatient opioid detoxifications during his/her lifetime
- Has significant suicidal ideation or behavior within the past year
- Is currently participating, or has participated, in a clinical trial of an investigational drug, device, or biologics within 3 months prior to screening
- Has a history of accidental opioid drug overdose in the past 3 years whether or not medical treatment was sought or received
- Is court mandated to receive treatment for opioid use disorder
- Additional criteria may apply
Sites / Locations
- North Country Clinical Research
- NRC Research Institute
- Atlantic Shores Hospital
- TRY Research
- Research Centers of America
- CNS Healthcare
- Neuroscience Research Institute
- John Hopkins University School of Medicine
- Comprehensive Clinical Research
- PRA Health Sciences
- New York State Psychiatric Institute/ Columbia University
- Duke University Medical Center
- Neuro-Behavioral Clinical Research, Inc.
- Midwest Clinical Research Center, LLC
- University Of Pennsylvania - Treatment Research Center
- Western Psychiatric Institute and Clinic of UPMC
- Community Clinical Research, Inc.
- Insite Clinical Research
- Baylor College of Medicine
- Pharmaceutical Research Associates Inc.
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Placebo Comparator
Arm Label
NTX/BUP
NTX/PBO-B
PBO-N/PBO-B
Arm Description
Oral naltrexone + sublingual buprenorphine
Oral naltrexone + sublingual placebo
Oral placebo naltrexone + sublingual placebo buprenorphine
Outcomes
Primary Outcome Measures
Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection
Toleration to the injection was 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 of Less Than or Equal to 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.
Mean Peak COWS Score During Treatment Period Prior to 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.
Area Under the Curve (AUC) COWS Score During the Treatment Period Prior to 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. To determine the daily AUC COWS score, a curve was generated by plotting the COWS scores against the time the test was taken. The area under this curve was calculated using the linear trapezoidal rule. For the total AUC COWS score, the AUCs calculated for each day during the treatment period were added together. To normalize for time, the total AUC COWS score was then divided by the number of days with daily AUC COWS score during the treatment period. The AUC COWS has a different range than the standard scale as it measures not the score itself, but the area under the curve of the score plotted against time.
Mean Score for Desire of Opioids During Treatment Period Prior to VIVITROL Injection
The Desire for Opioids Visual Analog Scale (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". Subjects placed a vertical line on the scale to indicate their desire for opioids at that particular time.
Incidence of Adverse Effects
The number of subjects who experienced treatment-emergent Adverse Events.
Area Under the Curve SOWS Score During the Treatment Period Prior to the VIVITROL Injection
The Subjective Opiate Withdrawal Scale (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). To determine the daily AUC SOWS score, a curve was generated by plotting the SOWS scores against the time the test was taken. The area under this curve was calculated using the linear trapezoidal rule. For the total AUC SOWS score, the AUCs calculated for each day during the treatment period were added together. To normalize for time, the total AUC SOWS score was then divided by the number of days with daily AUC SOWS score during the treatment period. The AUC SOWS has a different range than the standard scale as it measures not the score itself, but the area under the curve of the score plotted against time.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02537574
Brief Title
Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Prior to First Dose of VIVITROL® (Naltrexone for Extended-Release Injectable Suspension)
Official Title
A Phase 3 Study to Evaluate the Safety, Tolerability, and Efficacy of Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Prior to First Dose of VIVITROL®
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
August 2015 (Actual)
Primary Completion Date
October 27, 2016 (Actual)
Study Completion Date
January 9, 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 safety, effectiveness and tolerance of low doses of oral naltrexone along with buprenorphine to treat opioid use disorder prior to the first injection 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
Alkermes, Buprenorphine, Naltrexone, Vivitrol, Opioid Use, Opiates, Dependence, Abuse, Heroin, Painkillers, Substance Abuse
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
380 (Actual)
8. Arms, Groups, and Interventions
Arm Title
NTX/BUP
Arm Type
Experimental
Arm Description
Oral naltrexone + sublingual buprenorphine
Arm Title
NTX/PBO-B
Arm Type
Active Comparator
Arm Description
Oral naltrexone + sublingual placebo
Arm Title
PBO-N/PBO-B
Arm Type
Placebo Comparator
Arm Description
Oral placebo naltrexone + sublingual placebo buprenorphine
Intervention Type
Drug
Intervention Name(s)
NTX/BUP
Intervention Description
Daily doses
Intervention Type
Drug
Intervention Name(s)
NTX/PBO-B
Intervention Description
Daily doses
Intervention Type
Drug
Intervention Name(s)
PBO-N/PBO-B
Intervention Description
Daily doses
Primary Outcome Measure Information:
Title
Proportion of Subjects Who Receive and Tolerate a VIVITROL Injection
Description
Toleration to the injection was 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
1 week
Secondary Outcome Measure Information:
Title
Proportion of Days With COWS Peak Score of Less Than or Equal to 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
Mean Peak COWS Score During Treatment Period Prior to 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
Area Under the Curve (AUC) COWS Score During the Treatment Period Prior to 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. To determine the daily AUC COWS score, a curve was generated by plotting the COWS scores against the time the test was taken. The area under this curve was calculated using the linear trapezoidal rule. For the total AUC COWS score, the AUCs calculated for each day during the treatment period were added together. To normalize for time, the total AUC COWS score was then divided by the number of days with daily AUC COWS score during the treatment period. The AUC COWS has a different range than the standard scale as it measures not the score itself, but the area under the curve of the score plotted against time.
Time Frame
The COWS was administered 4-6 times per day during the Treatment Period (Days 1-7)
Title
Mean Score for Desire of Opioids During Treatment Period Prior to VIVITROL Injection
Description
The Desire for Opioids Visual Analog Scale (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". Subjects placed a vertical line on the scale to indicate their desire for opioids at that particular time.
Time Frame
1 week
Title
Incidence of Adverse Effects
Description
The number of subjects who experienced treatment-emergent Adverse Events.
Time Frame
Up to 92 days
Title
Area Under the Curve SOWS Score During the Treatment Period Prior to the VIVITROL Injection
Description
The Subjective Opiate Withdrawal Scale (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). To determine the daily AUC SOWS score, a curve was generated by plotting the SOWS scores against the time the test was taken. The area under this curve was calculated using the linear trapezoidal rule. For the total AUC SOWS score, the AUCs calculated for each day during the treatment period were added together. To normalize for time, the total AUC SOWS score was then divided by the number of days with daily AUC SOWS score during the treatment period. The AUC SOWS has a different range than the standard scale as it measures not the score itself, but the area under the curve of the score plotted against time.
Time Frame
The SOWS was administered 4-6 times per day during the Treatment Period
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 BMI of 18.0-40.0 kg/m^2
Has a physiologic dependence on opioids
Is voluntarily seeking treatment for opioid use disorder and willing to completely withdraw from his/her opioid use throughout the study with desire for or motivation for antagonist therapy
Wiling 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 used Buprenorphine within 7 days prior to randomization
Has used Methadone within 14 days prior to randomization
Has a history of VIVITROL use within 90 days prior to screening or has used oral naltrexone within 14 days prior to randomization
Has a history of seizures or has received anticonvulsant therapy within the past 5 years
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, or Naloxone
Has a history of more than 3 unsuccessful inpatient or medically assisted outpatient opioid detoxifications during his/her lifetime
Has significant suicidal ideation or behavior within the past year
Is currently participating, or has participated, in a clinical trial of an investigational drug, device, or biologics within 3 months prior to screening
Has a history of accidental opioid drug overdose in the past 3 years whether or not medical treatment was sought or received
Is court mandated to receive treatment for opioid use disorder
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
North Country Clinical Research
City
Oceanside
State/Province
California
ZIP/Postal Code
92056
Country
United States
Facility Name
NRC Research Institute
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Atlantic Shores Hospital
City
Lauderhill
State/Province
Florida
ZIP/Postal Code
33308
Country
United States
Facility Name
TRY Research
City
Maitland
State/Province
Florida
ZIP/Postal Code
84107
Country
United States
Facility Name
Research Centers of America
City
Oakland Park
State/Province
Florida
ZIP/Postal Code
33334
Country
United States
Facility Name
CNS Healthcare
City
Orlando
State/Province
Florida
ZIP/Postal Code
32801
Country
United States
Facility Name
Neuroscience Research Institute
City
Winfield
State/Province
Illinois
ZIP/Postal Code
60190
Country
United States
Facility Name
John Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Facility Name
Comprehensive Clinical Research
City
Berlin
State/Province
New Jersey
ZIP/Postal Code
08009
Country
United States
Facility Name
PRA Health Sciences
City
Marlton
State/Province
New Jersey
ZIP/Postal Code
08053
Country
United States
Facility Name
New York State Psychiatric Institute/ Columbia University
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
Neuro-Behavioral Clinical Research, Inc.
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
Midwest Clinical Research Center, LLC
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45417
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 UPMC
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Community Clinical Research, Inc.
City
Austin
State/Province
Texas
ZIP/Postal Code
78754
Country
United States
Facility Name
Insite Clinical Research
City
DeSoto
State/Province
Texas
ZIP/Postal Code
75115
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Pharmaceutical Research Associates Inc.
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
32751
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
29674251
Citation
Bisaga A, Mannelli P, Yu M, Nangia N, Graham CE, Tompkins DA, Kosten TR, Akerman SC, Silverman BL, Sullivan MA. Outpatient transition to extended-release injectable naltrexone for patients with opioid use disorder: A phase 3 randomized trial. Drug Alcohol Depend. 2018 Jun 1;187:171-178. doi: 10.1016/j.drugalcdep.2018.02.023. Epub 2018 Apr 10.
Results Reference
result
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
Learn more about this trial
Naltrexone for Use in Conjunction With Buprenorphine in Adults With Opioid Use Disorder Prior to First Dose of VIVITROL® (Naltrexone for Extended-Release Injectable Suspension)
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