A Randomized Acceptability and Safety Study of the Transfer From Subutex to Suboxone in Opioid- Dependent Subjects (Study P04843)(COMPLETED)

• Sponsor: Indivior Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00605033
• Collaborator: (none)
• Enrollment: 241
• Arms: 2
• Duration (Months): 14

Study Details

Study Description

Brief Summary

Post-marketing commitment to the European Medicines Agency to conduct a prospective, controlled study of the transfer from Subutex to Suboxone.

Condition or Disease	Intervention/Treatment	Phase
Opiate Dependence; Drug Dependence	Drug: Suboxone, Buprenorphine Hydrochloride + Naloxone, SCH 484; Drug: Subutex, Buprenorphine Hydrochloride, SCH 28444	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 241 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Acceptability and Safety Study of the Transfer From Subutex to Suboxone in Opioid- Dependent Subjects
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Suboxone Double-blind, once-daily sublingual Suboxone (buprenorphine/naloxone 4 mg/1 mg to 24 mg/6 mg) plus matching Subutex placebo during Week 1 followed by open-label, once-daily sublingual Suboxone (buprenorphine/naloxone 4 mg/1 mg to 24 mg/6 mg) during Weeks 2-4 with weekly access to take-home doses as of Week 2.	Drug: Suboxone, Buprenorphine Hydrochloride + Naloxone, SCH 484; Suboxone sublingual tablet 4 mg/1 mg - 24 mg/6 mg, daily for 28 days
Active Comparator: Subutex Double-blind, once-daily sublingual Subutex (buprenorphine 4 mg to 24 mg) plus matching Suboxone placebo during Week 1 followed by open-label, once-daily sublingual Subutex (buprenorphine 4 mg to 24 mg) during Weeks 2-4 with weekly access to take-home doses as of Week 2.	Drug: Subutex, Buprenorphine Hydrochloride, SCH 28444; Subutex sublingual tablet 4-24 mg, daily for 28 days

Outcome Measures

Primary Outcome Measures

1. Response Rate [Assessed by Day 7 of double-blind, double-dummy treatment period.]

   Response rate was defined as the percentage of participants who did not receive a dose increase from the dose given at the first dosing date by Day 7 of a one-week, randomized, double-blind, double-dummy treatment transfer phase.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must be males or non-pregnant, non-lactating females.

• Subjects must be at least 15 years of age, of either sex, and any race.

• Subjects (and/or the parent or guardian for subjects under the age of legal consent or who otherwise are unable to provide independent consent) must demonstrate willingness to participate in the study and to adhere to dose and visit schedules.

• Subjects must meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria(18) for opioid dependence.

• Subjects must have been receiving maintenance treatment with Subutex at doses ranging from 4 mg to the maximum dose permitted by country labeling requirements, but not to exceed 24 mg/day, for at least 1 month prior to screening.

• Subjects must not, according to self-report, have injected opioids more than four times in the month prior to screening.

• Subjects must have an opioid-negative urine drug screening (UDS) result prior to randomization.

• Each subject must confirm that he or she is practicing adequate contraception.

• Female subjects of childbearing potential must have a negative urine beta-human chorionic gonadotropin (β-hCG) test prior to enrollment in the study.

Exclusion Criteria:

• Subjects for whom treatment with either Subutex or Suboxone as required in the protocol would be inconsistent with national labeling.

• Subjects who are unwilling or unable to comply with the requirements of the protocol (eg, pending incarceration) or are in a situation or condition that, in the opinion of the investigator, may interfere with participation in the study.

• Subjects who are participating in any other clinical study in which medication(s) are being delivered.

• Subjects with known allergy or sensitivity to naloxone.

• Subjects who are on the staff, affiliated with, or a family member of the staff personnel directly involved with this study.

• Subjects must not have serious untreated Axis I DSM-IV-TR psychiatric comorbidity (eg, those who are actively suicidal or homicidal, have untreated schizophrenia, etc). Polysubstance abuse or dependence will not exclude subjects except in the case of unauthorized and significant benzodiazepine use requiring medical detoxification or alcohol dependence requiring medical detoxification.

• Human immunodeficiency virus (HIV)-positive subjects with clinical acquired immunodeficiency syndrome (AIDS).

• Subjects treated with generic buprenorphine.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Indivior Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Indivior Inc.
• ClinicalTrials.gov Identifier: NCT00605033
• Other Study ID Numbers: P04843; SWITCH
• First Posted: Jan 30, 2008
• Last Update Posted: Oct 21, 2016
• Last Verified: Sep 1, 2016

• Additional relevant MeSH terms: Opioid-Related Disorders; Substance-Related Disorders; Buprenorphine; Buprenorphine, Naloxone Drug Combination; Naloxone

Study Results

Participant Flow

Arm/Group Title	Suboxone	Subutex
Arm/Group Description	Double-blind, once-daily sublingual Suboxone (buprenorphine/naloxone 4 mg/1 mg to 24 mg/6 mg) plus matching Subutex placebo during Week 1 followed by open-label, once-daily sublingual Suboxone during Weeks 2-4 with weekly access to take-home doses as of Week 2.	Double-blind, once-daily sublingual Subutex (buprenorphine 4 mg to 24 mg) plus matching Suboxone placebo during Week 1 followed by open-label, once-daily sublingual Subutex during Weeks 2-4 with weekly access to take-home doses as of Week 2.
Period Title: Overall Study
STARTED	143	98
COMPLETED	136	90
NOT COMPLETED	7	8

Baseline Characteristics

Arm/Group Title	Suboxone	Subutex	Total
Arm/Group Description	Double-blind, once-daily sublingual Suboxone (buprenorphine/naloxone 4 mg/1 mg to 24 mg/6 mg) plus matching Subutex placebo during Week 1 followed by open-label, once-daily sublingual Suboxone during Weeks 2-4 with weekly access to take-home doses as of Week 2.	Double-blind, once-daily sublingual Subutex (buprenorphine 4 mg to 24 mg) plus matching Suboxone placebo during Week 1 followed by open-label, once-daily sublingual Subutex during Weeks 2-4 with weekly access to take-home doses as of Week 2.	Total of all reporting groups
Overall Participants	143	97	240
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.8 (8.2)	35.5 (8.7)	35.7 (8.4)
Sex: Female, Male (Count of Participants)
Female	30 21%	22 22.7%	52 21.7%
Male	113 79%	75 77.3%	188 78.3%

Outcome Measures

1. Primary Outcome

Title	Response Rate
Description	Response rate was defined as the percentage of participants who did not receive a dose increase from the dose given at the first dosing date by Day 7 of a one-week, randomized, double-blind, double-dummy treatment transfer phase.
Time Frame	Assessed by Day 7 of double-blind, double-dummy treatment period.

Outcome Measure Data

Analysis Population Description

Analysis of primary outcome was done on the intention-to-treat (ITT) population, defined as all randomized subjects who took at least one dose of study medication and provided at least one valid post-baseline assessment.

Arm/Group Title	Suboxone	Subutex
Arm/Group Description	Double-blind, once-daily sublingual Suboxone (buprenorphine/naloxone 4 mg/1 mg to 24 mg/6 mg) plus matching Subutex placebo during Week 1 followed by open-label, once-daily sublingual Suboxone during Weeks 2-4 with weekly access to take-home doses as of Week 2.	Double-blind, once-daily sublingual Subutex (buprenorphine 4 mg to 24 mg) plus matching Suboxone placebo during Week 1 followed by open-label, once-daily sublingual Subutex during Weeks 2-4 with weekly access to take-home doses as of Week 2.
Measure Participants	143	97
Number [Percentage of participants]	83.2 58.2%	88.7 91.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Suboxone, Subutex
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority was defined as a lower bound of the two-sided 95% confidence interval of the proportion difference greater than -0.15.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion difference
	Estimated Value	-0.054
	Confidence Interval	(2-Sided) 95%; -0.142 to 0.034
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Suboxone		Subutex
Arm/Group Description	Double-blind, once-daily sublingual Suboxone (buprenorphine/naloxone 4 mg/1 mg to 24 mg/6 mg) plus matching Subutex placebo during Week 1 followed by open-label, once-daily sublingual Suboxone during Weeks 2-4 with weekly access to take-home doses as of Week 2.		Double-blind, once-daily sublingual Subutex (buprenorphine 4 mg to 24 mg) plus matching Suboxone placebo during Week 1 followed by open-label, once-daily sublingual Subutex during Weeks 2-4 with weekly access to take-home doses as of Week 2.
All Cause Mortality
	Suboxone		Subutex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Suboxone		Subutex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/143 (1.4%)		4/97 (4.1%)
Blood and lymphatic system disorders
Normochromic normocytic anaemia	0/143 (0%)	0	1/97 (1%)	1
Gastrointestinal disorders
Melaena	0/143 (0%)	0	1/97 (1%)	1
Infections and infestations
Pneumonia	0/143 (0%)	0	1/97 (1%)	1
Injury, poisoning and procedural complications
Road traffic accident	0/143 (0%)	0	1/97 (1%)	1
Nervous system disorders
Coma	1/143 (0.7%)	1	0/97 (0%)	0
Epilepsy	1/143 (0.7%)	1	1/97 (1%)	1
Psychiatric disorders
Suicide attempt	1/143 (0.7%)	1	0/97 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pleural effusion	0/143 (0%)	0	1/97 (1%)	1
Surgical and medical procedures
Drug detoxification	0/143 (0%)	0	1/97 (1%)	1
Other (Not Including Serious) Adverse Events
	Suboxone		Subutex
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	79/143 (55.2%)		52/97 (53.6%)
Eye disorders
Lacrimation increased	9/143 (6.3%)	9	1/97 (1%)	1
Gastrointestinal disorders
Abdominal pain upper	9/143 (6.3%)	14	4/97 (4.1%)	5
Diarrhoea	8/143 (5.6%)	8	1/97 (1%)	1
Nausea	21/143 (14.7%)	29	7/97 (7.2%)	8
Toothache	1/143 (0.7%)	1	5/97 (5.2%)	5
General disorders
Asthenia	12/143 (8.4%)	15	7/97 (7.2%)	8
Chills	10/143 (7%)	11	7/97 (7.2%)	7
Fatigue	7/143 (4.9%)	8	5/97 (5.2%)	5
Musculoskeletal and connective tissue disorders
Myalgia	8/143 (5.6%)	9	7/97 (7.2%)	7
Nervous system disorders
Headache	23/143 (16.1%)	30	12/97 (12.4%)	15
Psychiatric disorders
Anxiety	23/143 (16.1%)	27	16/97 (16.5%)	17
Drug dependence	10/143 (7%)	11	4/97 (4.1%)	6
Restlessness	6/143 (4.2%)	6	5/97 (5.2%)	5
Insomnia	12/143 (8.4%)	12	10/97 (10.3%)	13
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	15/143 (10.5%)	16	6/97 (6.2%)	6
Yawning	12/143 (8.4%)	12	5/97 (5.2%)	5
Skin and subcutaneous tissue disorders
Hyperhidrosis	18/143 (12.6%)	28	9/97 (9.3%)	11
Piloerection	9/143 (6.3%)	10	2/97 (2.1%)	3
Vascular disorders
Hot flush	10/143 (7%)	12	5/97 (5.2%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigator will publish/present results together with other study sites, unless written permission is obtained from Sponsor. Investigator provides 45 days' written notice to Sponsor prior to submission for publication/presentation so that Sponsor can review copies of abstracts/manuscripts reporting results. Sponsor has the right to review/comment on any presentation regarding proprietary information, accuracy and fair balance of the information, and compliance with FDA regulations.