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A Randomized Acceptability and Safety Study of Suboxone Induction in Heroin Users (P05042)(COMPLETED)

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ClinicalTrials.gov Identifier: NCT00604188
Recruitment Status : Completed
First Posted : January 30, 2008
Results First Posted : May 6, 2011
Last Update Posted : July 2, 2017
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Conditions Opiate Dependence
Drug Dependence
Substance Dependence
Interventions Drug: Suboxone (SCH 000484)
Drug: Subutex (SCH 028444)
Enrollment 188
Recruitment Details 188 participants were recruited in this study.
Pre-assignment Details 188 participants were randomized in the study; however one did not receive any study medication. Therefore the intent-to-treat (ITT) population was 187 participants.
Arm/Group Title Direct Suboxone Induction Subutex-to-Suboxone Induction
Hide Arm/Group Description Participants received 8 mg of Suboxone and placebo Subutex on Day 1, 16 mg of Suboxone and placebo Subutex on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day. Participants received 8 mg Subutex and placebo Suboxone on Day 1, 16 mg Subutex and placebo Suboxone on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Period Title: Overall Study
Started 93 95 [1]
Completed 66 70
Not Completed 27 25
Reason Not Completed
Adverse Event             1             4
Lost to Follow-up             17             15
Withdrawal by Subject             5             1
Non-compliance with protocol             4             4
Did not receive study drug             0             1
[1]
The ITT population for Subutex-to-Suboxone Induction is 94 participants
Arm/Group Title Direct Suboxone Induction Subutex-to-Suboxone Induction Total
Hide Arm/Group Description Participants received 8 mg of Suboxone and placebo Subutex on Day 1, 16 mg of Suboxone and placebo Subutex on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day. Participants received 8 mg Subutex and placebo Suboxone on Day 1, 16 mg Subutex and placebo Suboxone on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day. Total of all reporting groups
Overall Number of Baseline Participants 93 94 187
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 93 participants 94 participants 187 participants
31  (8.4) 30.5  (8.2) 30.7  (8.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 93 participants 94 participants 187 participants
Female
21
  22.6%
25
  26.6%
46
  24.6%
Male
72
  77.4%
69
  73.4%
141
  75.4%
1.Primary Outcome
Title Responders at Day 3
Hide Description

Responders included the number of participants who received the scheduled dose of Suboxone at the Day 3 study visit. Participants who discontinued the study at Day 3 were considered non-responders.

All participants that continued the study received Suboxone tablets on Day 3.

Time Frame 3 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Direct Suboxone Induction Subutex-to-Suboxone Induction
Hide Arm/Group Description:
Participants received 8 mg of Suboxone and placebo Subutex on Day 1, 16 mg of Suboxone and placebo Subutex on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Participants received 8 mg Subutex and placebo Suboxone on Day 1, 16 mg Subutex and placebo Suboxone on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Overall Number of Participants Analyzed 93 94
Measure Type: Number
Unit of Measure: Participants
Responders 85 85
Non responders 8 9
2.Secondary Outcome
Title Illicit Opioid and Non-opioid Drug Use: Urine Drug Screen (UDS)
Hide Description Number of participants who tested negative on UDS during open-label phase on Day 28. The drugs screened on Day 28 included amphetamines, methamphetamines, cocaine, morphine, methadone, benzodiazepines, and tetrahydrocannabinol. Buprenorphine was only tested at screening and randomization according to protocol, therefore no values for buprenorphine are available for Day 28.
Time Frame 28 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants with missing data were not included in the analysis.
Arm/Group Title Direct Suboxone Induction Subutex-to-Suboxone Induction
Hide Arm/Group Description:
Participants received 8 mg of Suboxone and placebo Subutex on Day 1, 16 mg of Suboxone and placebo Subutex on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Participants received 8 mg Subutex and placebo Suboxone on Day 1, 16 mg Subutex and placebo Suboxone on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Overall Number of Participants Analyzed 79 82
Measure Type: Number
Unit of Measure: Participants
Tetrahydrocannabinol 65 59
Cocaine 70 69
Amphetamines 77 81
Benzodiazepines 59 64
Methamphetamines 79 80
Morphine 66 67
Methadone 76 81
Buprenorphine NA [1]  NA [1] 
[1]
Per protocol, buprenorphine testing was not performed on Day 28.
3.Secondary Outcome
Title Illicit Opioid and Non-opioid Drug Use: Substance Use Inventory (SUI)
Hide Description Number of participants with intravenous use of drug as measured by self-reported SUI from Days 3-28. The SUI form consisted of questions addressing the number of days and times a drug was used, and the route of drug use. For suboxone the use of scheduled study medication was not considered illicit use.
Time Frame Days 3 to 28
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Direct Suboxone Induction Subutex-to-Suboxone Induction
Hide Arm/Group Description:
Participants received 8 mg of Suboxone and placebo Subutex on Day 1, 16 mg of Suboxone and placebo Subutex on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Participants received 8 mg Subutex and placebo Suboxone on Day 1, 16 mg Subutex and placebo Suboxone on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Overall Number of Participants Analyzed 93 94
Measure Type: Number
Unit of Measure: Participants
Subutex - Non prescription source 0 0
Suboxone - Non prescription source 0 0
Suboxone - Illicit use from study supplies 0 0
Heroin 12 14
Other opioids 0 0
Methadone 0 0
Methamphetamine 0 0
Cocaine 2 4
Benzodiazepines/Tranquilizers 0 0
4.Secondary Outcome
Title Self-reported Opioid Withdrawal Symptoms (SOWS)
Hide Description SOWS were 16 items whose intensity was scored on a scale from 0 (not at all) to 4 (extremely) for a maximum possible score of 64. A total score of 0 represented the best outcome and a score of 64 represented the worst outcome. Participants were scored for SOWS at baseline (prior to randomization) and on Day 28. Reported are the scores for Day 28, and the change in scores from baseline to Day 28.
Time Frame Baseline and 28 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants with SOWS data reviewed for completeness and within visit date consistency were analyzed.
Arm/Group Title Direct Suboxone Induction Subutex-to-Suboxone Induction
Hide Arm/Group Description:
Participants received 8 mg of Suboxone and placebo Subutex on Day 1, 16 mg of Suboxone and placebo Subutex on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Participants received 8 mg Subutex and placebo Suboxone on Day 1, 16 mg Subutex and placebo Suboxone on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Overall Number of Participants Analyzed 69 72
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Score on Day 28 3.8  (6.77) 3.4  (5.95)
Change from Baseline to Day 28 -23.3  (14.1) -21.9  (13.4)
5.Secondary Outcome
Title Observer-rated Opioid Withdrawal Symptoms (OOWS)
Hide Description The OOWS were 13 physically observable signs that were present (scored 1) or absent (scored 0). A total score of 0 represented the best outcome and a total score of 13 represented the worst outcome. Participants were scored for OOWS at baseline (prior to randomization) and on Day 28. Reported are the total score for Day 28, and the change in scores from baseline to Day 28.
Time Frame Baseline and 28 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants with OOWS data reviewed for completeness and within visit date consistency were analyzed.
Arm/Group Title Direct Suboxone Induction Subutex-to-Suboxone Induction
Hide Arm/Group Description:
Participants received 8 mg of Suboxone and placebo Subutex on Day 1, 16 mg of Suboxone and placebo Subutex on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Participants received 8 mg Subutex and placebo Suboxone on Day 1, 16 mg Subutex and placebo Suboxone on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Overall Number of Participants Analyzed 69 72
Mean (Standard Deviation)
Unit of Measure: Score on a scale
OOWS Score on Day 28 0.6  (1.36) 0.5  (0.87)
Change from Baseline -5.9  (3.19) -5.9  (3.24)
6.Secondary Outcome
Title Addiction-related Severity Index (ASI-Lite): A Composite Score to Evaluate Seven Potential Problem Areas: Medical, Employment/Support Status, Alcohol, Drug, Legal, Family/Social, and Psychiatric
Hide Description

The ASI-Lite is a standardized, multidimensional, semi-structured, comprehensive interview that estimates addiction-related problem severity profiles in seven domains commonly affected in substance abusers. ASI-lite composite score ranges from 0 (worst outcome) to 1 (best outcome) for each category. Reported here is the change in ASI-Lite from baseline to Day 28.

The original drug use accounts for heroin, methadone, other opiates, analgesics, medicine/pills, cocaine, amphetamines, cannabis, hallucinogens, and inhalants. Modified drug use accounts for heroin, methadone, cocaine, and cannabis.

Time Frame Baseline and 28 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population.
Arm/Group Title Direct Suboxone Induction Subutex-to-Suboxone Induction
Hide Arm/Group Description:
Participants received 8 mg of Suboxone and placebo Subutex on Day 1, 16 mg of Suboxone and placebo Subutex on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Participants received 8 mg Subutex and placebo Suboxone on Day 1, 16 mg Subutex and placebo Suboxone on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Overall Number of Participants Analyzed 93 94
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
Medical -0.05  (0.027) -0.05  (0.027)
Employment -0.04  (0.034) -0.02  (0.033)
Employment satisfaction -0.10  (0.030) -0.01  (0.029)
Alcohol use -0.03  (0.017) -0.01  (0.017)
Drug use (Original) -0.24  (0.018) -0.23  (0.017)
Drug use (Modified) -0.36  (0.021) -0.34  (0.021)
Legal status -0.09  (0.026) -0.08  (0.025)
Family/Social relations -0.10  (0.040) -0.10  (0.041)
Other Family/Social relations -0.08  (0.027) -0.06  (0.026)
Psychiatric -0.12  (0.025) -0.08  (0.024)
7.Secondary Outcome
Title Compliance Rate
Hide Description Compliance rate was calculated as the number of days study medication was taken divided by the number of days study medication should have been taken X 100. The number of days study medication should have been taken was equal to the duration of treatment.
Time Frame 28 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Direct Suboxone Induction Subutex-to-Suboxone Induction
Hide Arm/Group Description:
Participants received 8 mg of Suboxone and placebo Subutex on Day 1, 16 mg of Suboxone and placebo Subutex on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Participants received 8 mg Subutex and placebo Suboxone on Day 1, 16 mg Subutex and placebo Suboxone on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Overall Number of Participants Analyzed 93 94
Mean (Standard Deviation)
Unit of Measure: Percentage of days
98.7  (4.22) 98.4  (6.25)
8.Secondary Outcome
Title Responders at Day 28
Hide Description Responders were the number of participants in each group who received the scheduled 8- to 24-mg dose of Suboxone at study visit day. A participant who discontinued from the study was treated as a non-responder at the timepoint after the participant discontinued.
Time Frame 28 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title Direct Suboxone Induction Subutex-to-Suboxone Induction
Hide Arm/Group Description:
Participants received 8 mg of Suboxone and placebo Subutex on Day 1, 16 mg of Suboxone and placebo Subutex on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Participants received 8 mg Subutex and placebo Suboxone on Day 1, 16 mg Subutex and placebo Suboxone on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
Overall Number of Participants Analyzed 93 94
Measure Type: Number
Unit of Measure: Participants
Responder 46 55
Non-responder 47 39
Time Frame [Not Specified]
Adverse Event Reporting Description The population analyzed is the ITT population
 
Arm/Group Title Direct Suboxone Induction Subutex-to-Suboxone Induction
Hide Arm/Group Description Participants received 8 mg of Suboxone and placebo Subutex on Day 1, 16 mg of Suboxone and placebo Subutex on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day. Participants received 8 mg Subutex and placebo Suboxone on Day 1, 16 mg Subutex and placebo Suboxone on Day 2, and all participants received open label Suboxone from Day 3 to Day 28. Suboxone dosage may be titrated from Day 4 to Day 28 up to 24 mg per day.
All-Cause Mortality
Direct Suboxone Induction Subutex-to-Suboxone Induction
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Direct Suboxone Induction Subutex-to-Suboxone Induction
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/93 (1.08%)      3/94 (3.19%)    
Infections and infestations     
ABSCESS LIMB  1  0/93 (0.00%)  0 1/94 (1.06%)  1
Nervous system disorders     
EPILEPSY  1  0/93 (0.00%)  0 1/94 (1.06%)  1
Psychiatric disorders     
DEPRESSION  1  1/93 (1.08%)  1 0/94 (0.00%)  0
DRUG DEPENDENCE  1  1/93 (1.08%)  1 0/94 (0.00%)  0
PERSONALITY DISORDER  1  1/93 (1.08%)  1 0/94 (0.00%)  0
Skin and subcutaneous tissue disorders     
RASH  1  0/93 (0.00%)  0 1/94 (1.06%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Direct Suboxone Induction Subutex-to-Suboxone Induction
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   61/93 (65.59%)      64/94 (68.09%)    
Gastrointestinal disorders     
ABDOMINAL PAIN  1  5/93 (5.38%)  5 4/94 (4.26%)  5
ABDOMINAL PAIN UPPER  1  1/93 (1.08%)  1 6/94 (6.38%)  7
NAUSEA  1  8/93 (8.60%)  9 14/94 (14.89%)  15
TOOTHACHE  1  6/93 (6.45%)  6 1/94 (1.06%)  1
VOMITING  1  15/93 (16.13%)  16 11/94 (11.70%)  12
General disorders     
ASTHENIA  1  8/93 (8.60%)  8 5/94 (5.32%)  6
CHILLS  1  3/93 (3.23%)  3 6/94 (6.38%)  6
FEELING COLD  1  7/93 (7.53%)  7 10/94 (10.64%)  10
Musculoskeletal and connective tissue disorders     
MYALGIA  1  7/93 (7.53%)  8 11/94 (11.70%)  12
Nervous system disorders     
HEADACHE  1  7/93 (7.53%)  10 9/94 (9.57%)  10
SOMNOLENCE  1  10/93 (10.75%)  11 7/94 (7.45%)  9
Psychiatric disorders     
ANXIETY  1  19/93 (20.43%)  24 16/94 (17.02%)  17
DRUG DEPENDENCE  1  16/93 (17.20%)  20 10/94 (10.64%)  15
INSOMNIA  1  25/93 (26.88%)  27 26/94 (27.66%)  30
RESTLESSNESS  1  8/93 (8.60%)  8 5/94 (5.32%)  6
Respiratory, thoracic and mediastinal disorders     
RHINORRHOEA  1  7/93 (7.53%)  7 5/94 (5.32%)  5
Skin and subcutaneous tissue disorders     
HYPERHIDROSIS  1  22/93 (23.66%)  25 21/94 (22.34%)  25
Vascular disorders     
HOT FLUSH  1  5/93 (5.38%)  5 4/94 (4.26%)  5
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.1
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.
The disclosure restriction on the PI cannot publish an individual study until a publication disclosing results from multicenter studies is published. The sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 45 days from the time submitted to the sponsor for review.
Results Point of Contact
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme Corp.
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00604188     History of Changes
Other Study ID Numbers: P05042
First Submitted: January 17, 2008
First Posted: January 30, 2008
Results First Submitted: December 7, 2010
Results First Posted: May 6, 2011
Last Update Posted: July 2, 2017