Trial Outcomes & Findings for ALK21-013: Efficacy and Safety of Medisorb® Naltrexone (VIVITROL®) in Adults With Opioid Dependence (NCT NCT00678418)

Last Updated: 2017-02-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

250 participants

Primary outcome timeframe

20 weeks

Results posted on

2017-02-10

Participant Flow

Participant milestones

Participant milestones
Measure	VIVITROL® 380 mg Single intramuscular (IM) injection administered every 4 weeks	Placebo Single intramuscular (IM) injection administered every 4 weeks
Part A (Double Blind) STARTED	126	124
Part A (Double Blind) COMPLETED	67	47
Part A (Double Blind) NOT COMPLETED	59	77
Part B (Open Label) STARTED	114	0
Part B (Open Label) COMPLETED	71	0
Part B (Open Label) NOT COMPLETED	43	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	VIVITROL® 380 mg n=126 Participants Single intramuscular (IM) injection administered every 4 weeks	Placebo n=124 Participants Single intramuscular (IM) injection administered every 4 weeks	Total n=250 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	126 Participants n=5 Participants	124 Participants n=7 Participants	250 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	29.4 years STANDARD_DEVIATION 4.8 • n=5 Participants	29.7 years STANDARD_DEVIATION 3.6 • n=7 Participants	29.6 years STANDARD_DEVIATION 4.2 • n=5 Participants
Gender Female	13 Participants n=5 Participants	17 Participants n=7 Participants	30 Participants n=5 Participants
Gender Male	113 Participants n=5 Participants	107 Participants n=7 Participants	220 Participants n=5 Participants
Region of Enrollment Russian Federation	126 participants n=5 Participants	124 participants n=7 Participants	250 participants n=5 Participants

PRIMARY outcome

Timeframe: 20 weeks

Population: Analyses include all randomized subjects who received at least 1 dose of study drug (Intent-to-treat \[ITT\] population).

Outcome measures

Outcome measures
Measure	VIVITROL® 380 mg n=126 Participants Single intramuscular (IM) injection administered every 4 weeks	Placebo n=124 Participants Single intramuscular (IM) injection administered every 4 weeks
Percentage (%) of Opioid-free Weeks Per Subject in Double-blind Period (Part A)	90.0 Percentage of opioid-free weeks Inter-Quartile Range 40.1 • Interval 20.0 to 100.0	35.0 Percentage of opioid-free weeks Inter-Quartile Range 43.3 • Interval 0.0 to 95.0

SECONDARY outcome

Timeframe: 168 days (24 weeks)

Population: Analyses include all randomized subjects who received at least 1 dose of study drug (ITT population).

Defined as the duration of study participation and calculated as the number of days from Dose 1 to the day of study discontinuation.

Outcome measures

Outcome measures
Measure	VIVITROL® 380 mg n=126 Participants Single intramuscular (IM) injection administered every 4 weeks	Placebo n=124 Participants Single intramuscular (IM) injection administered every 4 weeks
Days to Discontinuation During Part A	NA Days to study discontinuation The median estimate for VIVITROL is \>168 days (the duration of the treatment period). The median and confidence interval cannot be estimated because less than 50% of VIVITROL subjects discontinued during the 168-day treatment period.	96.0 Days to study discontinuation Interval 63.0 to 165.0

SECONDARY outcome

Timeframe: Baseline to 6 months (24 weeks)

Population: Analyses include all randomized subjects who received at least 1 dose of study drug (ITT population).

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").

Outcome measures

Outcome measures
Measure	VIVITROL® 380 mg n=126 Participants Single intramuscular (IM) injection administered every 4 weeks	Placebo n=124 Participants Single intramuscular (IM) injection administered every 4 weeks
Craving Score: Change From Baseline	-10.087 Units on a scale Interval -12.333 to -7.84	0.654 Units on a scale Interval -3.139 to 4.446

SECONDARY outcome

Timeframe: 24 Weeks

Population: Analyses include all randomized subjects who received at least 1 dose of study drug (ITT population).

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.

Outcome measures

Outcome measures
Measure	VIVITROL® 380 mg n=126 Participants Single intramuscular (IM) injection administered every 4 weeks	Placebo n=124 Participants Single intramuscular (IM) injection administered every 4 weeks
Incidence of Subjects Who Relapsed to Physiologic Opioid Dependence During the 24-week Treatment Period (Part A)	46.8 Percentage of participants who relapsed	62.1 Percentage of participants who relapsed

SECONDARY outcome

Timeframe: 24 Weeks

Population: Analyses include all randomized subjects who received at least 1 dose of study drug (ITT population). Change from baseline was calculated per subject as the percent of subjects' self-reported opioid-free days in Part A minus the percent of opioid-free days prior to the subjects' hospitalization for pre-study detoxification.

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.

Outcome measures

Outcome measures
Measure	VIVITROL® 380 mg n=126 Participants Single intramuscular (IM) injection administered every 4 weeks	Placebo n=124 Participants Single intramuscular (IM) injection administered every 4 weeks
Change in Percentage of Self-reported Opioid-free Days From Baseline to Week 24	75.83 Percentage of opioid-free days Interval 32.14 to 100.0	46.43 Percentage of opioid-free days Interval 11.01 to 96.76

Adverse Events

VIVITROL® 380 mg

Serious events: 3 serious events

Other events: 63 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	VIVITROL® 380 mg n=126 participants at risk Single intramuscular (IM) injection administered every 4 weeks	Placebo n=124 participants at risk Single intramuscular (IM) injection administered every 4 weeks
Infections and infestations Acquired immunodeficiency syndrome	0.79% 1/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.00% 0/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Infections and infestations Acute sinusitis	0.00% 0/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.81% 1/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Infections and infestations Adnexitis	0.79% 1/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.00% 0/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Infections and infestations HIV infection WHO clinical stage III	0.79% 1/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.00% 0/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Infections and infestations Herpes virus infection	0.79% 1/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.00% 0/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Infections and infestations Lobar pneumonia	0.00% 0/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.81% 1/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Psychiatric disorders Drug dependence	0.00% 0/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.81% 1/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Psychiatric disorders Psychotic disorder	0.00% 0/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.81% 1/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Gastrointestinal disorders Peptic ulcer	0.00% 0/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.81% 1/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.

Other adverse events

Additional Information

Bernard L. Silverman, MD

Alkermes, Inc.

Phone: 1-781-609-6000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee No individual investigator may publish results until after the publication of the overall study without receiving Alkermes' written approval. After that time, a PI/Institution may publish results for noncommercial purposes. Should an investigator wish to do so, the Sponsor will have 30 days to review the proposed publication. The PI/Institution will delete any Sponsor Confidential Information other than study results and will revise a publication based on regulatory requirements of the Sponsor.
Publication restrictions are in place

Restriction type: OTHER

Measure	VIVITROL® 380 mg n=126 participants at risk Single intramuscular (IM) injection administered every 4 weeks	Placebo n=124 participants at risk Single intramuscular (IM) injection administered every 4 weeks
Investigations Alanine aminotransferase increased	12.7% 16/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	5.6% 7/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Investigations Aspartate aminotransferase increased	10.3% 13/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	2.4% 3/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Investigations Gamma-glutamyl transferase increased	7.1% 9/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	3.2% 4/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Infections and infestations Nasopharyngitis	7.1% 9/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	2.4% 3/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Infections and infestations Influenza	4.8% 6/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	4.0% 5/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Psychiatric disorders Insomnia	6.3% 8/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.81% 1/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
General disorders Injection site pain	4.8% 6/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.81% 1/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Gastrointestinal disorders Toothache	4.0% 5/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	1.6% 2/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Gastrointestinal disorders Hypertension	4.8% 6/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	3.2% 4/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Nervous system disorders Headache	3.2% 4/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	2.4% 3/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Respiratory, thoracic and mediastinal disorders Respiratory tract infection	1.6% 2/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	1.6% 2/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Psychiatric disorders Drug dependence	0.79% 1/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	1.6% 2/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Gastrointestinal disorders Nausea	0.79% 1/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	1.6% 2/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
General disorders Pyrexia	0.79% 1/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	1.6% 2/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Investigations Transaminases increased	2.4% 3/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.00% 0/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Infections and infestations Bronchitis	0.00% 0/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	1.6% 2/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Investigations Hepatic enzyme increased	0.00% 0/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	1.6% 2/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Investigations Blood creatine phosphokinase increased	2.4% 3/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.81% 1/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Respiratory, thoracic and mediastinal disorders Pharyngolarnygeal pain	1.6% 2/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.00% 0/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.
Investigations Protein total increased	1.6% 2/126 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.	0.00% 0/124 • 6 Months (Part A) All participants who received at least 1 dose of randomized, double-blinded study drug (VIVITROL or placebo) are included in the safety population for Part A. Adverse events were tallied by number of participants affected as opposed to number of incidences reported for a given preferred term.