Trial Outcomes & Findings for ALK21-018: Effects of Medisorb® Naltrexone (VIVITROL®) on Alcohol Craving in Treatment-seeking, Alcohol-dependent Adults (NCT NCT00511836)

Last Updated: 2017-07-11

Results Overview

As was standard among fMRI studies conducted at the study site at the time, a change in BOLD signal in the range of 5% to 6% in anterior cingulate as measured using a 3T magnet,is considered highly significant in block-designed experiments.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

31 participants

Primary outcome timeframe

14 days (Baseline to Day 14)

Results posted on

2017-07-11

Participant Flow

Subjects were enrolled at a single clinical study center. The first subject was enrolled in July 2007. The last subject was enrolled in May 2009.

Screening evaluations were conducted during a 1-week period. All screening evaluations were to be completed at least 2 days before randomization and dosing.

Participant milestones

Participant milestones
Measure	VIVITROL 380 mg VIVITROL 380 mg (naltrexone for extended-release injectable suspension) - single administration via intramuscular (IM) injection on Day 1	Placebo Placebo matching VIVITROL 380 mg - single administration via intramuscular injection on Day 1
Double-blind Period STARTED	16	15
Double-blind Period COMPLETED	15	15
Double-blind Period NOT COMPLETED	1	0
Optional Open-label VIVITROL (2 Months) STARTED	22	0
Optional Open-label VIVITROL (2 Months) COMPLETED	6	0
Optional Open-label VIVITROL (2 Months) NOT COMPLETED	16	0

Reasons for withdrawal

Reasons for withdrawal
Measure	VIVITROL 380 mg VIVITROL 380 mg (naltrexone for extended-release injectable suspension) - single administration via intramuscular (IM) injection on Day 1	Placebo Placebo matching VIVITROL 380 mg - single administration via intramuscular injection on Day 1
Double-blind Period Lost to Follow-up	1	0

Baseline Characteristics

ALK21-018: Effects of Medisorb® Naltrexone (VIVITROL®) on Alcohol Craving in Treatment-seeking, Alcohol-dependent Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	VIVITROL 380 mg n=16 Participants VIVITROL 380 mg (naltrexone for extended-release injectable suspension) - single administration via intramuscular (IM) injection on Day 1	Placebo n=15 Participants Placebo matching VIVITROL 380 mg - single administration via intramuscular injection on Day 1	Total n=31 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants	15 Participants n=7 Participants	31 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	48.3 years STANDARD_DEVIATION 8.8 • n=5 Participants	44.8 years STANDARD_DEVIATION 9.5 • n=7 Participants	46.6 years STANDARD_DEVIATION 9.2 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment United States	16 participants n=5 Participants	15 participants n=7 Participants	31 participants n=5 Participants

PRIMARY outcome

Timeframe: 14 days (Baseline to Day 14)

Population: Analyses include all randomized, dosed subjects who had functional magnetic resolution imaging (fMRI) on Day 14. No data were imputed.

Outcome measures

Outcome measures
Measure	VIVITROL 380 mg n=15 Participants VIVITROL 380 mg (naltrexone for extended-release injectable suspension) - single administration via intramuscular (IM) injection on Day 1	Placebo n=13 Participants Placebo matching VIVITROL 380 mg - single administration via intramuscular injection on Day 1
Change From Baseline in Blood Oxygen-level-dependent (BOLD) Signal Activation Values Detected in the Reward Circuitry of the Brain in Alcohol-dependent Subjects After Presentation of Alcohol-related Cues.	0.041 Percentage (%) of Change Standard Deviation 0.036	-0.044 Percentage (%) of Change Standard Deviation 0.049

PRIMARY outcome

Timeframe: 14 days (Baseline to Day 14)

Population: Analyses include all randomized, dosed subjects who had functional magnetic resolution imaging (fMRI) on Day 14. No data were imputed.

Outcome measures

Outcome measures
Measure	VIVITROL 380 mg n=15 Participants VIVITROL 380 mg (naltrexone for extended-release injectable suspension) - single administration via intramuscular (IM) injection on Day 1	Placebo n=13 Participants Placebo matching VIVITROL 380 mg - single administration via intramuscular injection on Day 1
Change From Baseline in BOLD Signal Activation Values for the Inferior Frontal Gyrus	0.001 Percentage (%) of Change Standard Deviation 0.055	-0.067 Percentage (%) of Change Standard Deviation 0.078

PRIMARY outcome

Timeframe: 14 days (Baseline to Day 14)

Population: Analyses include all randomized, dosed subjects who had functional magnetic resolution imaging (fMRI) on Day 14. No data were imputed.

Outcome measures

Outcome measures
Measure	VIVITROL 380 mg n=15 Participants VIVITROL 380 mg (naltrexone for extended-release injectable suspension) - single administration via intramuscular (IM) injection on Day 1	Placebo n=13 Participants Placebo matching VIVITROL 380 mg - single administration via intramuscular injection on Day 1
Change From Baseline in BOLD Signal Activation Values in the Reward Circuitry	-0.018 Percentage (%) of Change Standard Deviation 0.105	-0.060 Percentage (%) of Change Standard Deviation 0.074

SECONDARY outcome

Timeframe: 28 days (Baseline to Day 28)

Population: All randomized subjects who received at least 1 dose of study drug and had an Obsessive-Compulsive Drinking Scale (OCDS) assessment at Day 28 were included in this analysis. No last-observation-carried-forward (LOCF) approach was used.

There are 14 items on the Obsessive Compulsive Drinking Scale (OCDS). The scale is scored from 0 to 40 (units). A score of 0 units indicates no obsession-compulsion with respect to alcohol (best score). A score of 40 units indicates maximum obsession-compulsion with respect to alcohol (worst score). A negative Change from Baseline value indicates an improvement. For scoring methods, see: Anton RF, Moak DH, Latham P (1995), The Obsessive Compulsive Drinking Scale: A self-rated instrument for the quantification of thoughts about alcohol and drinking behavior. Alcohol Clin Exp Res 19:92-9.

Outcome measures

Outcome measures
Measure	VIVITROL 380 mg n=15 Participants VIVITROL 380 mg (naltrexone for extended-release injectable suspension) - single administration via intramuscular (IM) injection on Day 1	Placebo n=15 Participants Placebo matching VIVITROL 380 mg - single administration via intramuscular injection on Day 1
Change From Baseline in Obsessive-Compulsive Drinking Scale (OCDS) Score in Alcohol-dependent Subjects	-8.5 Change in OCDS score Standard Deviation 5.7	-7.3 Change in OCDS score Standard Deviation 6.4

SECONDARY outcome

Timeframe: 28 days (Baseline to Day 28)

Population: All randomized subjects who received at least 1 dose of study drug and had a craving score assessment at Day 28 were included in this analysis. No last-observation-carried-forward (LOCF) approach was used.

The Actiwatch-Score device (MiniMitter Co.) was used to collect data on daily alcohol craving. The Actiwatch device is a wrist-worn, battery-operated monitor programmed to beep every 3 hours ±20 minutes, to signal the subjects to enter their alcohol craving or desire to use alcohol at that exact moment on a scale of 0 to 10 units: 0 indicates no craving at all (best score) and 10 indicates extreme craving (worst score). A negative result for Change in Baseline at Day 28 indicates an improvement in daily craving as of 1 month after study drug administration.

Outcome measures

Outcome measures
Measure	VIVITROL 380 mg n=14 Participants VIVITROL 380 mg (naltrexone for extended-release injectable suspension) - single administration via intramuscular (IM) injection on Day 1	Placebo n=15 Participants Placebo matching VIVITROL 380 mg - single administration via intramuscular injection on Day 1
Change From Baseline in Daily Craving Score in Alcohol-dependent Subjects (Actiwatch Data)	-0.846 Change in Daily Craving Score Standard Deviation 0.881	-0.789 Change in Daily Craving Score Standard Deviation 0.986

Adverse Events

VIVITROL 380 mg (Double-blind Period)

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo (Double-blind Period)

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Optional Open-label VIVITROL Period (2 Months)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Bernard L. Silverman

Alkermes, Inc.

Phone: 781-609-6000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The PI/Institution may publish study results for noncommercial purposes. Sponsor will have 30 days to review a proposed publication. PI/Institution will delete any Sponsor Confidential Information other than study results, will revise a publication based on regulatory requirements of Sponsor as manufacture of the study drug, and will delay publication for no more than 60 days to allow for filing of patent applications to protect Sponsor's intellectual property contained in such publication.
Publication restrictions are in place

Restriction type: OTHER

Other adverse events
Measure	VIVITROL 380 mg (Double-blind Period) n=16 participants at risk VIVITROL 380 mg (naltrexone for extended-release injectable suspension). Data are described for the initial 28-day double-blind period.	Placebo (Double-blind Period) n=15 participants at risk Placebo for VIVITROL 380 mg. Data are described for the initial 28-day double-blind period.	Optional Open-label VIVITROL Period (2 Months) n=22 participants at risk Following the 28-day, double-blind treatment period, all subjects were offered a chance to receive open-label VIVITROL for an additional 2 months (2 injections, each separated by 1 month). Safety data are described for all subjects in the VIVITROL open-label period, regardless of the treatment received (VIVITROL or placebo) for the first month.
General disorders Injection site pain	6.2% 1/16 • 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.	20.0% 3/15 • 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.	0.00% 0/22 • 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.
General disorders Injection site induration	12.5% 2/16 • 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.	0.00% 0/15 • 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.	0.00% 0/22 • 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.
Injury, poisoning and procedural complications Head injury	6.2% 1/16 • 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.	0.00% 0/15 • 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.	0.00% 0/22 • 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.
General disorders Injection site abcess	0.00% 0/16 • 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.	6.7% 1/15 • 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.	0.00% 0/22 • 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.
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/16 • 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.	6.7% 1/15 • 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.	0.00% 0/22 • 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.
Nervous system disorders Headache	0.00% 0/16 • 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.	20.0% 3/15 • 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.	0.00% 0/22 • 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.
Nervous system disorders Dizziness	12.5% 2/16 • 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.	0.00% 0/15 • 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.	0.00% 0/22 • 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.
Nervous system disorders Lethargy	6.2% 1/16 • 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.	0.00% 0/15 • 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.	0.00% 0/22 • 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.
Psychiatric disorders Insomnia	6.2% 1/16 • 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.	6.7% 1/15 • 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.	4.5% 1/22 • 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.
Psychiatric disorders Abnormal dreams	0.00% 0/16 • 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.	6.7% 1/15 • 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.	0.00% 0/22 • 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.
Psychiatric disorders Anxiety	6.2% 1/16 • 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.	0.00% 0/15 • 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.	0.00% 0/22 • 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.
Psychiatric disorders Euphoric mood	6.2% 1/16 • 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.	0.00% 0/15 • 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.	0.00% 0/22 • 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.
General disorders Irritability	0.00% 0/16 • 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.	6.7% 1/15 • 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.	0.00% 0/22 • 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.
Psychiatric disorders Libido decreased	0.00% 0/16 • 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.	6.7% 1/15 • 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.	0.00% 0/22 • 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.
Reproductive system and breast disorders Sexual dysfunction	6.2% 1/16 • 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.	0.00% 0/15 • 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.	0.00% 0/22 • 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.
Psychiatric disorders Alcohol withdrawal syndrome	0.00% 0/16 • 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.	0.00% 0/15 • 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.	4.5% 1/22 • 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.
Psychiatric disorders Hallucinations, visual	0.00% 0/16 • 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.	0.00% 0/15 • 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.	4.5% 1/22 • 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.
Gastrointestinal disorders Nausea	6.2% 1/16 • 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.	20.0% 3/15 • 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.	4.5% 1/22 • 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.
General disorders Fatigue	0.00% 0/16 • 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.	6.7% 1/15 • 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.	4.5% 1/22 • 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.
General disorders Pain	0.00% 0/16 • 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.	0.00% 0/15 • 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.	4.5% 1/22 • 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.
Infections and infestations Nasopharyngitis	6.2% 1/16 • 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.	6.7% 1/15 • 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.	0.00% 0/22 • 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.
Infections and infestations Influenza	0.00% 0/16 • 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.	0.00% 0/15 • 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.	4.5% 1/22 • 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.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/16 • 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.	6.7% 1/15 • 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.	0.00% 0/22 • 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.
Ear and labyrinth disorders Ear congestion	6.2% 1/16 • 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.	0.00% 0/15 • 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.	0.00% 0/22 • 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.
Investigations Chest x-ray abnormal	0.00% 0/16 • 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.	6.7% 1/15 • 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.	0.00% 0/22 • 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.
Investigations Alanine aminotransferase increased	0.00% 0/16 • 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.	0.00% 0/15 • 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.	4.5% 1/22 • 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.
Investigations Aspartate aminotransferase increased	0.00% 0/16 • 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.	0.00% 0/15 • 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.	4.5% 1/22 • 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.
Investigations Blood alkaline phosphate increased	0.00% 0/16 • 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.	0.00% 0/15 • 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.	4.5% 1/22 • 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.
Investigations Blood pressure increased	0.00% 0/16 • 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.	0.00% 0/15 • 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.	4.5% 1/22 • 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.
Investigations Gamma-glutamyltransferase increased	0.00% 0/16 • 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.	0.00% 0/15 • 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.	4.5% 1/22 • 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.
Vascular disorders Haematemesis	0.00% 0/16 • 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.	6.7% 1/15 • 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.	0.00% 0/22 • 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.
Metabolism and nutrition disorders Hypertriglyceridaemia	0.00% 0/16 • 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.	0.00% 0/15 • 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.	4.5% 1/22 • 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.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/16 • 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.	6.7% 1/15 • 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.	0.00% 0/22 • 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.