This was a study of the effects of VIVITROL® on alcohol cue-induced craving and the associated brain activation patterns in alcohol-dependent adults who had recently completed alcohol detoxification and were seeking further treatment for their alcohol dependence. The study was powered to to detect whether VIVITROL attenuates or blocks the BOLD signal increases in response to alcohol-related cues.

In the double-blind portion, subjects received a single administration of study drug (VIVITROL 380 mg or placebo). Subjects who completed the double-blind portion could opt to continue to the open-label portion and receive 2 additional months of treatment with VIVITROL 380 mg.

The double-blind phase consisted of 6 visits over a 5- to 6-week period and included 2 telephone contacts and 2 functional magnetic resonance imaging (fMRI) scans.

The optional open-label extension included 2 visits approximately 1 month apart. Subjects who completed both phases participated in a total of 8 scheduled visits (including 2 fMRI scans and 2 telephone contacts) over a period of up to 14 weeks.

At screening, eligible, consenting subjects were given an Actiwatch®-Score device. They were instructed to record their alcohol craving using this device throughout the double-blind phase. The Actiwatch was programmed to beep every 3 hours ±20 minutes, thereby signaling the subjects to enter their craving or desire to use alcohol, at that exact moment, on a scale of 0 to 10 (with 0 being no craving at all and 10 being extreme craving). In addition, subjects entered any drug and/or alcohol use at the time of occurrence. The Actiwatch was not utilized in the open-label portion of the study.

Primary Inclusion Criteria:

• Current diagnosis of alcohol dependence, meeting at least 3 criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. (DSM-IV)
• Recently completed alcohol detoxification and seeking treatment for alcohol dependence
• Women of childbearing potential must agree to use an approved method of contraception for study duration

Primary Exclusion Criteria:

• Pregnancy or lactation
• Evidence of hepatic failure including: ascites, bilirubin >10% above upper limit of normal (ULN) and/or esophageal variceal disease
• Current dependence (within the past year) to benzodiazepines or cocaine, or current or history of opioid dependence according to DSM-IV criteria
• Use of any opioids and/or methadone within 14 days prior to the screening visit, or likely to require opioid therapy during the study period
• Previous enrollment in a VIVITROL clinical trial or previous VIVITROL experience
• Known intolerance and/or hypersensitivity to naltrexone, carboxymethylcellulose, or polylactide-co-glycolide (PLG)
• Parole, probation, or pending legal proceedings having the potential for incarceration during the study period

From the time of consent, adverse events (AEs) were monitored continuously in each subject until 30 days after his or her last administration of study drug.

In the open-label period, VIVITROL was administered in an unblinded manner to subjects who chose to continue in this optional extension; there was no control group in the open-label phase.

The study was powered to detect whether VIVITROL blocks the fMRI BOLD signal increase in response to alcohol-related cues as compared to placebo. Results of the secondary endpoints should be interpreted with caution.