ALK21-013: Efficacy and Safety of Medisorb® Naltrexone (VIVITROL®) in Adults With Opioid Dependence

• ClinicalTrials.gov Identifier: NCT00678418
• Recruitment Status: Completed
• First Posted: May 15, 2008
• Results First Posted: January 21, 2011
• Last Update Posted: February 10, 2017
• Sponsor: Alkermes, Inc.
• Information provided by (Responsible Party): Alkermes, Inc.

Study Description

Brief Summary:

This is a Phase 3 multi-center trial designed to evaluate the clinical efficacy and safety of VIVITROL® (Medisorb® naltrexone 380 mg) versus placebo when administered to adults upon discharge from inpatient treatment for opioid dependence.

The study was conducted in 2 parts, Part A and Part B. The clinical portion of both parts has completed. Results for Part B are not yet available.

Condition or disease	Intervention/treatment	Phase
Opiate Dependence	Drug: VIVITROL® 380 mg; Drug: Placebo	Phase 3

Detailed Description:

Part A was a double-blind, randomized, placebo-controlled assessment of the efficacy and safety of 24 weeks of monthly treatment with VIVITROL compared to placebo in opioid-dependent adults.

Subjects who completed Part A could choose to continue to Part B, which was an open-label extension to assess longer-term safety, durability of effect, health economics, and quality of life (QOL) in the continuing study population for up to 1 year.

At the conclusion of both parts, each completing subject will have received a total of up to 19 injections of study drug over approximately 1.5 years.

Dosing was performed by the principal investigator or designated study staff member.

All subjects received standardized, manual-based psychosocial support at each scheduled visit. Opioid use was tracked through urine drug testing and subjects' self reports. Other evaluations for efficacy and safety, health economics, and quality of life were routinely conducted throughout the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of VIVITROL® (Naltrexone for Extended-release Injectable Suspension) in Adults With Opioid Dependence
• Study Start Date: June 2008
• Actual Primary Completion Date: October 2009
• Actual Study Completion Date: November 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: VIVITROL® 380 mg	Drug: VIVITROL® 380 mg; Administered via intramuscular (IM) injection once every 4 weeks for 24 weeks during Part A, followed by once every 4 weeks for 52 weeks in Part B.; Other Names: Naltrexone for extended-release injectable suspension; Medisorb® naltrexone
Placebo Comparator: Placebo	Drug: Placebo; Administered via IM injection once every 4 weeks for 24 weeks during Part A, followed by VIVITROL® 380 mg via IM injection once every 4 weeks for 52 weeks in Part B.

Outcome Measures

Primary Outcome Measures :

1. Percentage (%) of Opioid-free Weeks Per Subject in Double-blind Period (Part A) [ Time Frame: 20 weeks ]
   Included are data from the last 20 weeks of the 24-week double-blind treatment period (Part A). Response profiles for each Arm are based on subjects' individual rates of weekly opioid-free data, including negative urine test results, attendance at study visits, and self-reports of opioid use/non-use.

Secondary Outcome Measures :

1. Days to Discontinuation During Part A [ Time Frame: 168 days (24 weeks) ]
   Defined as the duration of study participation and calculated as the number of days from Dose 1 to the day of study discontinuation.
2. Craving Score: Change From Baseline [ Time Frame: Baseline to 6 months (24 weeks) ]
   Measured using subjects' response on a validated Visual Analog Scale at prespecified weekly visits throughout Part A, with comparison of baseline to end of Part A. The scale ranged from 0 ("No craving") to 100 ("highest possible craving").
3. Incidence of Subjects Who Relapsed to Physiologic Opioid Dependence During the 24-week Treatment Period (Part A) [ Time Frame: 24 Weeks ]
   Assessment of relapse to physiologic opioid dependence was based on individual subjects' results on the naloxone challenge test. A positive naloxone challenge test result was considered as a relapse to physiologic opioid dependence.
4. Change in Percentage of Self-reported Opioid-free Days From Baseline to Week 24 [ Time Frame: 24 Weeks ]
   Opioid use was measured using subjects' entries on a validated Timeline FollowBack (TLFB) calendar in which they recorded their use/non-use of opioids each day.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Primary Inclusion Criteria:

• Written, informed consent
• 18 years of age or older
• Current diagnosis of opioid dependence, based on Diagnostic and Statistical Manual of Mental Health Disorders, 4th Ed. (DSM-IV-TR) criteria
• Voluntarily seeking treatment for opioid dependence
• Completing or recently completed up to 30 days of inpatient treatment for opioid detoxification, and off all opioids (including buprenorphine and methadone) for at least 7 days
• Noncustodial, stable residence and phone, plus 1 contact with verifiable address and phone
• Significant other (eg, spouse, relative) willing to supervise compliance with the study visit schedule and procedures
• Agree to use contraception for study duration if of childbearing potential

Primary Exclusion Criteria:

• Pregnancy or lactation
• Clinically significant medical condition or observed abnormalities (eg: physical exam, electrocardiogram (ECG), lab and/or urinalysis findings)
• Positive naloxone challenge test at randomization (Day 0)
• Evidence of hepatic failure including: ascites, bilirubin >10% above upper limit of normal (ULN) and/or esophageal variceal disease
• Past or present history of an acquired immunodeficiency syndrome (AIDS)-indicator disease in HIV-infected subjects
• Active hepatitis and/or aspartate aminotransferase (AST), alanine aminotransferase(ALT) >3xULN
• Current major depression with suicidal ideation, psychosis, bipolar disorder, or any psychiatric disorder that would compromise ability to complete the study
• Recent history (within 6 months prior to screening) of suicidal ideation or attempt
• Dependence within prior year based on DSM-IV-TR, to any drugs other than prescription opioids or heroin, caffeine, marijuana, or nicotine
• Active alcohol dependence within prior 6 months
• Current alcohol use disorder that would, in the Investigator's opinion, preclude successful completion of the study
• Positive urine drug test for cocaine, benzodiazepines, or amphetamines at screening
• Use of oral naltrexone for 7 consecutive days within 60 days prior to screening
• Known intolerance and/or hypersensitivity to naltrexone, carboxymethylcellulose, or polylactide-co-glycolide (PLG)

Contacts and Locations

Locations

Russian Federation

Ethics Committee within the Federal Authority for Healthcare and Social Development Regulation

Moscow, Russian Federation, 109074

Sponsors and Collaborators

Alkermes, Inc.

Investigators

• Principal Investigator: Evgeny Krupitsky, Prof.; Leningrad Regional Addiction Center
• Principal Investigator: Ruslan Ilyuk, Dr.; Bekhterev Psychoneurological Research Institute
• Principal Investigator: Edvin Zvartau, Prof.; Saint-Petersburg State Medical University n.a. Pavlov
• Principal Investigator: Alexander Sofronov, Prof.; Saint-Petersburg Addiction Hospital
• Principal Investigator: Alexey Egorov, Prof.; Saint-Petersburg Addiction Hospital
• Principal Investigator: Alexander Okhapkin, Prof.; Addiction Treatment Center, Clinical Facility of Smolensk State Medical Academy
• Principal Investigator: Nikolay Bokhan, Prof.; Tomsk Mental Health Research Institute
• Principal Investigator: Vladimir Mendelevich, Prof.; Kazan State Medical University
• Principal Investigator: Yuri Sivolap, Prof.; Moscow Medical Academy n.a. I.M. Sechenov
• Principal Investigator: Oleg Eryshev, Prof.; Bekhterev Psychoneurological Research Institute
• Principal Investigator: Nikolay Ivanets, Prof.; National Addiction Scientific Center
• Principal Investigator: Vitaliy Sinitskiy, Prof.; Northern State Medical University
• Principal Investigator: Andrey Anipchenko, Dr.; Saint-Petersburg Addiction Hospital

More Information

Additional Information:

Trials Central clinical trials listing 

Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial 

Publications of Results:

Krupitsky E, Nunes EV, Ling W, Gastfriend DR, Memisoglu A, Silverman BL. Injectable extended-release naltrexone (XR-NTX) for opioid dependence: long-term safety and effectiveness. Addiction. 2013 Sep;108(9):1628-37. doi: 10.1111/add.12208. Epub 2013 May 24.

Nunes EV, Krupitsky E, Ling W, Zummo J, Memisoglu A, Silverman BL, Gastfriend DR. Treating Opioid Dependence With Injectable Extended-Release Naltrexone (XR-NTX): Who Will Respond? J Addict Med. 2015 May-Jun;9(3):238-43. doi: 10.1097/ADM.0000000000000125.

Mitchell MC, Memisoglu A, Silverman BL. Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. J Stud Alcohol Drugs. 2012 Nov;73(6):991-7.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Krupitsky E, Zvartau E, Blokhina E, Verbitskaya E, Wahlgren V, Tsoy-Podosenin M, Bushara N, Burakov A, Masalov D, Romanova T, Tyurina A, Palatkin V, Slavina T, Pecoraro A, Woody GE. Randomized trial of long-acting sustained-release naltrexone implant vs oral naltrexone or placebo for preventing relapse to opioid dependence. Arch Gen Psychiatry. 2012 Sep;69(9):973-81. doi: 10.1001/archgenpsychiatry.2012.1a.

Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet. 2011 Apr 30;377(9776):1506-13. doi: 10.1016/S0140-6736(11)60358-9.

• Responsible Party: Alkermes, Inc.
• ClinicalTrials.gov Identifier: NCT00678418
• Other Study ID Numbers: ALK21-013
• First Posted: May 15, 2008
• Results First Posted: January 21, 2011
• Last Update Posted: February 10, 2017
• Last Verified: December 2016

Keywords provided by Alkermes, Inc.:

Addiction; Opiate dependence; Inpatient detoxification; opioid dependence; heroin dependence

Additional relevant MeSH terms:

Opioid-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Naltrexone; Alcohol Deterrents; Narcotic Antagonists; Physiological Effects of Drugs; Sensory System Agents; Peripheral Nervous System Agents