Clinical trial NCT00678418: ALK21-013: Efficacy and Safety of Medisorb® Naltrexone (VIVITROL®) in Adults With Opioid Dependence
Official title: Efficacy and Safety of VIVITROL® (Naltrexone for Extended-release Injectable Suspension) in Adults With Opioid Dependence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Opiate Dependence
Keywords: Addiction
Opiate dependence
Inpatient detoxification
opioid dependence
heroin dependence
Lead sponsor: Alkermes, Inc.
Sponsor class: INDUSTRY
First posted: 2008-05-15
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Percentage (%) of Opioid-free Weeks Per Subject in Double-blind Period (Part A)
timeFrame: 20 weeks
Secondary outcomes:
measure: Days to Discontinuation During Part A
timeFrame: 168 days (24 weeks)
measure: Craving Score: Change From Baseline
timeFrame: Baseline to 6 months (24 weeks)
measure: Incidence of Subjects Who Relapsed to Physiologic Opioid Dependence During the 24-week Treatment Period (Part A)
timeFrame: 24 Weeks
measure: Change in Percentage of Self-reported Opioid-free Days From Baseline to Week 24
timeFrame: 24 Weeks
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Ethics Committee within the Federal Authority for Healthcare and Social Development Regulation
Study officials:
affiliation: Leningrad Regional Addiction Center
name: Evgeny Krupitsky, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Bekhterev Psychoneurological Research Institute
name: Ruslan Ilyuk, Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Saint-Petersburg State Medical University n.a. Pavlov
name: Edvin Zvartau, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Saint-Petersburg Addiction Hospital
name: Alexander Sofronov, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Saint-Petersburg Addiction Hospital
name: Alexey Egorov, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Addiction Treatment Center, Clinical Facility of Smolensk State Medical Academy
name: Alexander Okhapkin, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Tomsk Mental Health Research Institute
name: Nikolay Bokhan, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Kazan State Medical University
name: Vladimir Mendelevich, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Moscow Medical Academy n.a. I.M. Sechenov
name: Yuri Sivolap, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Bekhterev Psychoneurological Research Institute
name: Oleg Eryshev, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Addiction Scientific Center
name: Nikolay Ivanets, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Northern State Medical University
name: Vitaliy Sinitskiy, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Saint-Petersburg Addiction Hospital
name: Andrey Anipchenko, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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. doi: 10.15288/jsad.2012.73.991.
citation: 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.
citation: 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.