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)

Opioid Use Disorder Clinical Trial

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®

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02537574
• Other study ID #: ALK6428-A301
• Status: Completed
• Phase: Phase 3
• Start date: August 2015
• Est. completion date: January 9, 2017

Study information

• Verified date: March 2019
• Source: Alkermes, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 380
• Est. completion date: January 9, 2017
• Est. primary completion date: October 27, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Disease
• Opioid Use Disorder
• Substance-Related Disorders

Intervention

Drug:
• NTX/BUP
Daily doses
• NTX/PBO-B
Daily doses
• PBO-N/PBO-B
Daily doses

Locations

Country	Name	City	State
United States	Community Clinical Research, Inc.	Austin	Texas
United States	John Hopkins University School of Medicine	Baltimore	Maryland
United States	Comprehensive Clinical Research	Berlin	New Jersey
United States	Neuro-Behavioral Clinical Research, Inc.	Canton	Ohio
United States	Midwest Clinical Research Center, LLC	Dayton	Ohio
United States	Insite Clinical Research	DeSoto	Texas
United States	Duke University Medical Center	Durham	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Atlantic Shores Hospital	Lauderhill	Florida
United States	TRY Research	Maitland	Florida
United States	PRA Health Sciences	Marlton	New Jersey
United States	New York State Psychiatric Institute/ Columbia University	New York	New York
United States	Research Centers of America	Oakland Park	Florida
United States	North Country Clinical Research	Oceanside	California
United States	NRC Research Institute	Orange	California
United States	CNS Healthcare	Orlando	Florida
United States	University Of Pennsylvania - Treatment Research Center	Philadelphia	Pennsylvania
United States	Western Psychiatric Institute and Clinic of UPMC	Pittsburgh	Pennsylvania
United States	Pharmaceutical Research Associates Inc.	Salt Lake City	Utah
United States	Neuroscience Research Institute	Winfield	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Alkermes, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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]	1 week
Secondary	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.	1 week
Secondary	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.	1 week
Secondary	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.	The COWS was administered 4-6 times per day during the Treatment Period (Days 1-7)
Secondary	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.	1 week
Secondary	Incidence of Adverse Effects	The number of subjects who experienced treatment-emergent Adverse Events.	Up to 92 days
Secondary	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.	The SOWS was administered 4-6 times per day during the Treatment Period