Trial Outcomes & Findings for ALK21-003: Study of Medisorb® Naltrexone (VIVITROL®) in Alcohol-Dependent Adults (NCT NCT01218958)

Last Updated: 2017-07-11

Results Overview

Drinking rates were assessed from participants' self-reports using the validated Timeline Follow-Back (TLFB) method. Using a TLFB calendar, participants reported the number of days they had consumed alcohol along with the amount they consumed on each day. A heavy drinking day was defined as ≥5 drinks/day for men and ≥4 drinks/day for women.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

624 participants

Primary outcome timeframe

Baseline through Week 24 (168 days)

Results posted on

2017-07-11

Participant Flow

Potential subjects were screened up to 14 days before administration of study drug (Study Day 0).

A dynamic randomization was implemented to optimize balancing treatment assignment for 4 prespecified factors: gender, subject's baseline goal of abstinence (ie, yes/no), presence of abstinence prior to randomization, and study site.

Participant milestones

Participant milestones
Measure	Medisorb Naltrexone 190 mg	Medisorb Naltrexone 380 mg	Placebo Groups (Pooled) Results for the two groups that received placebo were pooled together for reporting purposes.
Overall Study STARTED	210	205	209
Overall Study COMPLETED	126	124	128
Overall Study NOT COMPLETED	84	81	81

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

ALK21-003: Study of Medisorb® Naltrexone (VIVITROL®) in Alcohol-Dependent Adults

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Medisorb Naltrexone 190 mg n=210 Participants	Medisorb Naltrexone 380 mg n=205 Participants	Placebo Groups (Pooled) n=209 Participants Results for the two groups that received placebo were pooled together for reporting purposes.	Total n=624 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	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	203 Participants n=5 Participants	200 Participants n=7 Participants	199 Participants n=5 Participants	602 Participants n=4 Participants
Age, Categorical >=65 years	7 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants	22 Participants n=4 Participants
Age, Continuous	44.6 years STANDARD_DEVIATION 10.8 • n=5 Participants	45.0 years STANDARD_DEVIATION 10.1 • n=7 Participants	44.7 years STANDARD_DEVIATION 10.8 • n=5 Participants	44.7 years STANDARD_DEVIATION 10.6 • n=4 Participants
Sex: Female, Male Female	68 Participants n=5 Participants	67 Participants n=7 Participants	66 Participants n=5 Participants	201 Participants n=4 Participants
Sex: Female, Male Male	142 Participants n=5 Participants	138 Participants n=7 Participants	143 Participants n=5 Participants	423 Participants n=4 Participants
Region of Enrollment United States	210 participants n=5 Participants	205 participants n=7 Participants	209 participants n=5 Participants	624 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline through Week 24 (168 days)

Population: The last post-baseline observation carried forward (LOCF) of each participant in the intent-to-treat population (all randomized participants who received at least 1 injection of study drug) were utilized for the primary efficacy analysis.

Outcome measures

Outcome measures
Measure	Medisorb Naltrexone 190 mg n=168 Days	Medisorb Naltrexone 380 mg n=168 Days	Placebo Groups (Pooled) n=168 Days Results for the two groups that received placebo were pooled together for reporting purposes.
Percentage of Heavy Drinking Days Over the Treatment Period	14.75 Percentage of days Interval 3.23 to 44.58	10.23 Percentage of days Interval 1.16 to 33.33	19.77 Percentage of days Interval 6.01 to 50.15

SECONDARY outcome

Timeframe: 24 weeks (Baseline to Week 24)

A TEAE is any adverse event, whether or not considered drug-related, that develops or worsens in severity after study drug administration begins (ie, from the first administration through the end of the follow-up period).

Outcome measures

Outcome measures
Measure	Medisorb Naltrexone 190 mg n=210 Participants	Medisorb Naltrexone 380 mg n=205 Participants	Placebo Groups (Pooled) n=209 Participants Results for the two groups that received placebo were pooled together for reporting purposes.
Number of Participants Reporting at Least 1 Treatment-emergent Adverse Event (TEAE)	190 Participants	187 Participants	181 Participants

Adverse Events

Medisorb Naltrexone 190 mg

Serious events: 10 serious events

Other events: 190 other events

Deaths: 0 deaths

Medisorb Naltrexone 380 mg

Serious events: 11 serious events

Other events: 187 other events

Deaths: 0 deaths

Placebo Groups (Pooled)

Serious events: 15 serious events

Other events: 181 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Bernard L. Silverman, VP, Clinical Development

Alkermes, Inc.

Phone: 781-609-6000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Should a PI wish to disclose results, the Sponsor will review the results communications prior to public release and can embargo results communications for a period of at least 30 days prior to the submission, for review and approval. Revisions will be negotiated in good faith by the Investigator and Sponsor and may be submitted for publication or disclosed by the Investigator only following receipt of written approval from the Sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	Medisorb Naltrexone 190 mg n=210 participants at risk	Medisorb Naltrexone 380 mg n=205 participants at risk	Placebo Groups (Pooled) n=209 participants at risk Results for the two groups that received placebo were pooled together for reporting purposes.
Psychiatric disorders Alcoholism	2.4% 5/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	2.0% 4/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	3.3% 7/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Psychiatric disorders Alcohol withdrawal syndrome	0.48% 1/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Psychiatric disorders Emotional distress	0.00% 0/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.48% 1/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Psychiatric disorders Psychotic disorder NOS	0.00% 0/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.48% 1/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Infections and infestations Pneumonia NOS	0.48% 1/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.48% 1/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Infections and infestations Interstitial pneumonia	0.00% 0/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.49% 1/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Cardiac disorders Atrial fibrillation aggravated	0.00% 0/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.48% 1/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Cardiac disorders Myocardial infarction	0.00% 0/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.49% 1/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Gastrointestinal disorders Gastrointestinal haemorrhage NOS	0.00% 0/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.49% 1/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Gastrointestinal disorders Perirectal abscess	0.00% 0/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.49% 1/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
General disorders Chest tightness	0.00% 0/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.49% 1/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
General disorders Fatigue	0.00% 0/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.48% 1/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Injury, poisoning and procedural complications Head injury	0.48% 1/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Injury, poisoning and procedural complications Jaw fracture	0.00% 0/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.48% 1/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Inflammatory carcinoma of the breast	0.00% 0/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.48% 1/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer NOS	0.48% 1/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Hepatobiliary disorders Cholelithiasis	0.48% 1/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Intervertebral disc herniation	0.00% 0/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.48% 1/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Pregnancy, puerperium and perinatal conditions Abortion missed	0.00% 0/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.49% 1/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Respiratory, thoracic and mediastinal disorders Eosinophilic pneumonia acute	0.00% 0/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.49% 1/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.00% 0/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.

Measure	Medisorb Naltrexone 190 mg n=210 participants at risk	Medisorb Naltrexone 380 mg n=205 participants at risk	Placebo Groups (Pooled) n=209 participants at risk Results for the two groups that received placebo were pooled together for reporting purposes.
Gastrointestinal disorders Nausea	25.2% 53/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	33.2% 68/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	11.0% 23/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Gastrointestinal disorders Diarrhoea NOS	11.0% 23/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	12.7% 26/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	8.6% 18/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Gastrointestinal disorders Vomiting NOS	10.5% 22/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	13.7% 28/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	5.7% 12/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Gastrointestinal disorders Abdominal pain upper	8.1% 17/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	3.9% 8/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	4.3% 9/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Gastrointestinal disorders Abdominal pain NOS	2.4% 5/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	6.3% 13/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	1.4% 3/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Gastrointestinal disorders Dyspepsia	2.4% 5/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	1.5% 3/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	5.3% 11/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
General disorders Injection site pain	9.0% 19/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	11.7% 24/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	5.7% 12/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
General disorders Fatigue	16.2% 34/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	20.0% 41/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	11.0% 23/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
General disorders Injection site induration	3.3% 7/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	6.3% 13/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	1.9% 4/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Infections and infestations Nasopharyngitis	15.2% 32/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	10.7% 22/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	11.0% 23/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Infections and infestations Upper respiratory tract infection NOS	7.1% 15/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	10.2% 21/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	8.6% 18/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Psychiatric disorders Insomnia	12.9% 27/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	13.7% 28/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	12.0% 25/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Psychiatric disorders Anxiety NEC	4.8% 10/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	6.3% 13/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	5.7% 12/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Psychiatric disorders Depression	1.4% 3/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	7.8% 16/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	3.8% 8/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Psychiatric disorders Libido decreased	1.4% 3/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	5.4% 11/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	0.96% 2/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Nervous system disorders Headache NOS	15.7% 33/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	22.0% 45/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	16.3% 34/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Nervous system disorders Dizziness	11.0% 23/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	12.7% 26/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	3.8% 8/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Arthralgia	5.2% 11/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	9.3% 19/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	4.3% 9/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	6.2% 13/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	4.4% 9/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	3.8% 8/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	2.9% 6/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	3.9% 8/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	5.3% 11/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Musculoskeletal and connective tissue disorders Pain in limb	0.95% 2/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	6.3% 13/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	2.9% 6/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.
Metabolism and nutrition disorders Appetite decreased NOS	5.7% 12/210 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	12.7% 26/205 • Events were recorded starting at baseline through 42 days after the last dose of study drug.	1.4% 3/209 • Events were recorded starting at baseline through 42 days after the last dose of study drug.