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

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ClinicalTrials.gov Identifier: NCT00678418
Recruitment Status : Completed
First Posted : May 15, 2008
Results First Posted : January 21, 2011
Last Update Posted : February 10, 2017
Sponsor:
Information provided by (Responsible Party):
Alkermes, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Opiate Dependence
Interventions Drug: VIVITROL® 380 mg
Drug: Placebo
Enrollment 250
Recruitment Details  
Pre-assignment Details  
Arm/Group Title VIVITROL® 380 mg Placebo
Hide Arm/Group Description Single intramuscular (IM) injection administered every 4 weeks Single intramuscular (IM) injection administered every 4 weeks
Period Title: Part A (Double Blind)
Started 126 124
Completed 67 47
Not Completed 59 77
Period Title: Part B (Open Label)
Started 114 [1] 0
Completed 71 0
Not Completed 43 0
[1]
All participants who received placebo in Part A were switched to open-label VIVITROL in Part B.
Arm/Group Title VIVITROL® 380 mg Placebo Total
Hide Arm/Group Description Single intramuscular (IM) injection administered every 4 weeks Single intramuscular (IM) injection administered every 4 weeks Total of all reporting groups
Overall Number of Baseline Participants 126 124 250
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 126 participants 124 participants 250 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
126
 100.0%
124
 100.0%
250
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 126 participants 124 participants 250 participants
29.4  (4.8) 29.7  (3.6) 29.6  (4.2)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 126 participants 124 participants 250 participants
Female
13
  10.3%
17
  13.7%
30
  12.0%
Male
113
  89.7%
107
  86.3%
220
  88.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Russian Federation Number Analyzed 126 participants 124 participants 250 participants
126 124 250
1.Primary Outcome
Title Percentage (%) of Opioid-free Weeks Per Subject in Double-blind Period (Part A)
Hide Description 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.
Time Frame 20 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses include all randomized subjects who received at least 1 dose of study drug (Intent-to-treat [ITT] population).
Arm/Group Title VIVITROL® 380 mg Placebo
Hide Arm/Group Description:
Single intramuscular (IM) injection administered every 4 weeks
Single intramuscular (IM) injection administered every 4 weeks
Overall Number of Participants Analyzed 126 124
Median (Inter-Quartile Range)
Unit of Measure: Percentage of opioid-free weeks
90.0
(20.0 to 100.0)
35.0
(0.0 to 95.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection VIVITROL® 380 mg, Placebo
Comments Null hypothesis = the distribution function of opioid-free weeks is the same for both treatment groups.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Van der Waerden
Comments [Not Specified]
2.Secondary Outcome
Title Days to Discontinuation During Part A
Hide Description Defined as the duration of study participation and calculated as the number of days from Dose 1 to the day of study discontinuation.
Time Frame 168 days (24 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses include all randomized subjects who received at least 1 dose of study drug (ITT population).
Arm/Group Title VIVITROL® 380 mg Placebo
Hide Arm/Group Description:
Single intramuscular (IM) injection administered every 4 weeks
Single intramuscular (IM) injection administered every 4 weeks
Overall Number of Participants Analyzed 126 124
Median (95% Confidence Interval)
Unit of Measure: Days to study discontinuation
NA [1] 
(NA to NA)
96.0
(63.0 to 165.0)
[1]
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.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection VIVITROL® 380 mg, Placebo
Comments P-value was calculated using the log-rank test for the null hypothesis: the distribution of days to discontinuation does not differ by treatment.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0042
Comments A total of 114 subjects continued on-study beyond the 168-day endpoint for Part A; these subjects were censored as of the first dosing day in Part B.
Method Kaplan Meier
Comments [Not Specified]
3.Secondary Outcome
Title Craving Score: Change From Baseline
Hide Description 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").
Time Frame Baseline to 6 months (24 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses include all randomized subjects who received at least 1 dose of study drug (ITT population).
Arm/Group Title VIVITROL® 380 mg Placebo
Hide Arm/Group Description:
Single intramuscular (IM) injection administered every 4 weeks
Single intramuscular (IM) injection administered every 4 weeks
Overall Number of Participants Analyzed 126 124
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Units on a scale
-10.087
(-12.333 to -7.840)
0.654
(-3.139 to 4.446)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection VIVITROL® 380 mg, Placebo
Comments

P-value was calculated using the Chi-square test for the null hypothesis: mean treatment difference = 0.

Calculations were based on the Generalized Estimating Equation (GEE) model (normal distribution, identity link and AR(1) correlation structure) for repeated data on change from baseline with treatment and visit as main effects, and baseline as a covariate. Missing data were imputed using the Last Observation Carried Forward (LOCF) method.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
4.Secondary Outcome
Title Incidence of Subjects Who Relapsed to Physiologic Opioid Dependence During the 24-week Treatment Period (Part A)
Hide Description 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.
Time Frame 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Analyses include all randomized subjects who received at least 1 dose of study drug (ITT population).
Arm/Group Title VIVITROL® 380 mg Placebo
Hide Arm/Group Description:
Single intramuscular (IM) injection administered every 4 weeks
Single intramuscular (IM) injection administered every 4 weeks
Overall Number of Participants Analyzed 126 124
Measure Type: Number
Unit of Measure: Percentage of participants who relapsed
46.8 62.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection VIVITROL® 380 mg, Placebo
Comments

Chi-square test was used to calculate the p-value for treatment. Null hypothesis = no association between relapse to dependence and study treatment.

Subjects who discontinued prematurely from the study were imputed as having a positive naloxone challenge test result.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0154
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.75
Confidence Interval 95%
0.60 to 0.95
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change in Percentage of Self-reported Opioid-free Days From Baseline to Week 24
Hide Description 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.
Time Frame 24 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title VIVITROL® 380 mg Placebo
Hide Arm/Group Description:
Single intramuscular (IM) injection administered every 4 weeks
Single intramuscular (IM) injection administered every 4 weeks
Overall Number of Participants Analyzed 126 124
Median (Inter-Quartile Range)
Unit of Measure: Percentage of opioid-free days
75.83
(32.14 to 100.00)
46.43
(11.01 to 96.76)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection VIVITROL® 380 mg, Placebo
Comments Null hypothesis: Treatment difference=0. Missing data from subjects due to early discontinuation during Part A were imputed using the baseline rate; thus data for subjects who discontinued early were imputed as having no change from baseline.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0031
Comments [Not Specified]
Method van der Waerden
Comments [Not Specified]
Time Frame 6 Months (Part A)
Adverse Event Reporting Description 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.
 
Arm/Group Title VIVITROL® 380 mg Placebo
Hide Arm/Group Description Single intramuscular (IM) injection administered every 4 weeks Single intramuscular (IM) injection administered every 4 weeks
All-Cause Mortality
VIVITROL® 380 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
VIVITROL® 380 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   3/126 (2.38%)   4/124 (3.23%) 
Gastrointestinal disorders     
Peptic ulcer  1  0/126 (0.00%)  1/124 (0.81%) 
Infections and infestations     
Acquired immunodeficiency syndrome  1  1/126 (0.79%)  0/124 (0.00%) 
Acute sinusitis  1  0/126 (0.00%)  1/124 (0.81%) 
Adnexitis  1  1/126 (0.79%)  0/124 (0.00%) 
HIV infection WHO clinical stage III  1  1/126 (0.79%)  0/124 (0.00%) 
Herpes virus infection  1  1/126 (0.79%)  0/124 (0.00%) 
Lobar pneumonia  1  0/126 (0.00%)  1/124 (0.81%) 
Psychiatric disorders     
Drug dependence  1  0/126 (0.00%)  1/124 (0.81%) 
Psychotic disorder  1  0/126 (0.00%)  1/124 (0.81%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
VIVITROL® 380 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   63/126 (50.00%)   40/124 (32.26%) 
Gastrointestinal disorders     
Toothache  1  5/126 (3.97%)  2/124 (1.61%) 
Hypertension  1  6/126 (4.76%)  4/124 (3.23%) 
Nausea  1  1/126 (0.79%)  2/124 (1.61%) 
General disorders     
Injection site pain  1  6/126 (4.76%)  1/124 (0.81%) 
Pyrexia  1  1/126 (0.79%)  2/124 (1.61%) 
Infections and infestations     
Nasopharyngitis  1  9/126 (7.14%)  3/124 (2.42%) 
Influenza  1  6/126 (4.76%)  5/124 (4.03%) 
Bronchitis  1  0/126 (0.00%)  2/124 (1.61%) 
Investigations     
Alanine aminotransferase increased  1  16/126 (12.70%)  7/124 (5.65%) 
Aspartate aminotransferase increased  1  13/126 (10.32%)  3/124 (2.42%) 
Gamma-glutamyl transferase increased  1  9/126 (7.14%)  4/124 (3.23%) 
Transaminases increased  1  3/126 (2.38%)  0/124 (0.00%) 
Hepatic enzyme increased  1  0/126 (0.00%)  2/124 (1.61%) 
Blood creatine phosphokinase increased  1  3/126 (2.38%)  1/124 (0.81%) 
Protein total increased  1  2/126 (1.59%)  0/124 (0.00%) 
Nervous system disorders     
Headache  1  4/126 (3.17%)  3/124 (2.42%) 
Psychiatric disorders     
Insomnia  1  8/126 (6.35%)  1/124 (0.81%) 
Drug dependence  1  1/126 (0.79%)  2/124 (1.61%) 
Respiratory, thoracic and mediastinal disorders     
Respiratory tract infection  1  2/126 (1.59%)  2/124 (1.61%) 
Pharyngolarnygeal pain  1  2/126 (1.59%)  0/124 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Bernard L. Silverman, MD
Organization: Alkermes, Inc.
Phone: 1-781-609-6000
Responsible Party: Alkermes, Inc.
ClinicalTrials.gov Identifier: NCT00678418     History of Changes
Other Study ID Numbers: ALK21-013
First Submitted: May 14, 2008
First Posted: May 15, 2008
Results First Submitted: December 20, 2010
Results First Posted: January 21, 2011
Last Update Posted: February 10, 2017