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

• 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.

• Study retention during the double-blind period [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
• Craving score [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
• Incidence of physiologic opioid dependence (physiologic dependence is defined as a positive naloxone challenge) [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
• Self-reported opioid use [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]

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.

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.

• 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
• 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.

• Experimental: VIVITROL® 380 mg
  Intervention: Drug: VIVITROL® 380 mg
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

• 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.

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)