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

Sponsor:	Alkermes
Information provided by (Responsible Party):	Alkermes
ClinicalTrials.gov Identifier:	NCT00678418

Purpose

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	Intervention	Phase
Opiate Dependence	Drug: VIVITROL® 380 mg Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Efficacy and Safety of VIVITROL® (Naltrexone for Extended-release Injectable Suspension) in Adults With Opioid Dependence

Resource links provided by NLM:

Drug Information available for: Naltrexone Naltrexone hydrochloride

U.S. FDA Resources

Further study details as provided by Alkermes:

Primary Outcome Measures:

Percentage (%) of Opioid-free Weeks Per Subject in Double-blind Period (Part A) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
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:

Days to Discontinuation During Part A [ Time Frame: 168 days (24 weeks) ] [ Designated as safety issue: No ]
Defined as the duration of study participation and calculated as the number of days from Dose 1 to the day of study discontinuation.
Craving Score: Change From Baseline [ Time Frame: Baseline to 6 months (24 weeks) ] [ Designated as safety issue: No ]
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").
Incidence of Subjects Who Relapsed to Physiologic Opioid Dependence During the 24-week Treatment Period (Part A) [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
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.
Change in Percentage of Self-reported Opioid-free Days From Baseline to Week 24 [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
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.

Enrollment:	250
Study Start Date:	June 2008
Study Completion Date:	November 2010
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00678418

Locations

Russian Federation
Ethics Committee within the Federal Authority for Healthcare and Social Development Regulation
Moscow, Russian Federation, 109074

Sponsors and Collaborators

Alkermes

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:

World Health Organization (WHO) international clinical trials search portal This link exits the ClinicalTrials.gov site

Trials Central clinical trials listing This link exits the ClinicalTrials.gov site

Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial This link exits the ClinicalTrials.gov site

No publications provided by Alkermes

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

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.

Responsible Party:	Alkermes
ClinicalTrials.gov Identifier:	NCT00678418 History of Changes
Other Study ID Numbers:	ALK21-013
Study First Received:	May 14, 2008
Results First Received:	December 20, 2010
Last Updated:	January 11, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Alkermes:

Addiction
Opiate dependence
Inpatient detoxification
opioid dependence
heroin dependence

Additional relevant MeSH terms:

Opioid-Related Disorders
Substance-Related Disorders
Mental Disorders
Naltrexone
Analgesics, Opioid
Narcotic Antagonists
Physiological Effects of Drugs

Pharmacologic Actions
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Therapeutic Uses
Analgesics
Central Nervous System Depressants

ClinicalTrials.gov processed this record on May 23, 2012