Trial Outcomes & Findings for Safety and Efficacy of Dose Conversion From Vicodin® to Buprenorphine Transdermal System (Butrans™) in Subjects With OA Pain (NCT NCT00312572)

Last Updated: 2012-09-03

Results Overview

The indicator variable was 1 = completion, and 0 = noncompletion. For the primary efficacy analysis, the percentage of subjects who completed the double-blind phase was computed with its 95% confidence interval (CI) for each treatment regimen (starting dose of BTDS 10 or BTDS 20) across and within baseline Vicodin® stratum (15 to 22.5mg/day vs \>22.5 to 30 mg/day as determined by the daily average hydrocodone dose during the run-in period).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

204 participants

Primary outcome timeframe

14 days

Results posted on

2012-09-03

Participant Flow

Study dates: 26-Jun-2003 (first patient first visit) to 21-Jul-2004 (last patient last visit) in 29 medical/research centers in the United States.

N = 266 subjects received a stable regimen of Vicodin® in the Run-in period and were eligible for randomization if they reported a daily "average pain over the last 24 hours" score of 0=none or 1=mild on at least 5 of the 7 days; and used ≤ 2 doses of supplemental analgesic per day for their osteoarthritic (OA) pain. N = 204 completed the run-in.

Participant milestones

Participant milestones
Measure	Double-blind BTDS 10/20 Initial doses (Level 1) of BTDS 10. Subjects were allowed to have their dose adjusted to BTDS 20 (Level 2) on or after day 4. Subjects remained on their treatment regimen until day 14 (± 2 days) or until they discontinued from the study. Downward titration was not permitted.	Double-blind BTDS 20 Initial doses (Level 1) of BTDS 20. Subjects remained on their treatment regimen until day 14 (± 2 days) or until they discontinued from the study. Downward titration was not permitted.
Overall Study STARTED	101	103
Overall Study COMPLETED	85	82
Overall Study NOT COMPLETED	16	21

Reasons for withdrawal

Reasons for withdrawal
Measure	Double-blind BTDS 10/20 Initial doses (Level 1) of BTDS 10. Subjects were allowed to have their dose adjusted to BTDS 20 (Level 2) on or after day 4. Subjects remained on their treatment regimen until day 14 (± 2 days) or until they discontinued from the study. Downward titration was not permitted.	Double-blind BTDS 20 Initial doses (Level 1) of BTDS 20. Subjects remained on their treatment regimen until day 14 (± 2 days) or until they discontinued from the study. Downward titration was not permitted.
Overall Study Adverse Event	10	16
Overall Study Lost to Follow-up	1	1
Overall Study Administrative	4	2
Overall Study Lack of Efficacy	1	2

Baseline Characteristics

Safety and Efficacy of Dose Conversion From Vicodin® to Buprenorphine Transdermal System (Butrans™) in Subjects With OA Pain

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Double-blind BTDS 10/20 n=101 Participants Initial doses (Level 1) of BTDS 10. Subjects were allowed to have their dose adjusted to BTDS 20 (Level 2) on or after day 4. Subjects remained on their treatment regimen until day 14 (± 2 days) or until they discontinued from the study. Downward titration was not permitted.	Double-blind BTDS 20 n=103 Participants Initial doses (Level 1) of BTDS 20. Subjects remained on their treatment regimen until day 14 (± 2 days) or until they discontinued from the study. Downward titration was not permitted.	Total n=204 Participants Total of all reporting groups
Age Continuous	57.4 years STANDARD_DEVIATION 10.10 • n=5 Participants	58.9 years STANDARD_DEVIATION 9.97 • n=7 Participants	58.2 years STANDARD_DEVIATION 10.04 • n=5 Participants
Sex: Female, Male Female	63 Participants n=5 Participants	73 Participants n=7 Participants	136 Participants n=5 Participants
Sex: Female, Male Male	38 Participants n=5 Participants	30 Participants n=7 Participants	68 Participants n=5 Participants

PRIMARY outcome

Timeframe: 14 days

Population: Full Analysis Population: (N = 198) consisted of all subjects who were randomized into the double-blind phase, received at least 1 dose of BTDS during the double-blind phase, and had at least 1 efficacy observation during the double-blind phase, and had no evidence of impaired liver function at screening and prerandomization.

Outcome measures

Outcome measures
Measure	Double-blind BTDS 10/20 n=98 Participants Initial doses (Level 1) of BTDS 10. Subjects were allowed to have their dose adjusted to BTDS 20 (Level 2) on or after day 4. Subjects remained on their treatment regimen until day 14 (± 2 days) or until they discontinued from the study. Downward titration was not permitted.	Double-blind BTDS 20 n=100 Participants Initial doses (Level 1) of BTDS 20. Subjects remained on their treatment regimen until day 14 (± 2 days) or until they discontinued from the study. Downward titration was not permitted.	Combined Total n=198 Participants Combined percentages from BTDS 10/20 and BTDS 20
The Percentage of Subjects Who Completed the 14-day Double-blind Phase. 15 - 22.5 mg HCD (Stratum 1)	88 Percentage of Participants Interval 79.9 to 95.1	83 Percentage of Participants Interval 74.7 to 91.9	85 Percentage of Participants Interval 79.7 to 91.2
The Percentage of Subjects Who Completed the 14-day Double-blind Phase. more than 22.5 - 30 mg HCD (Stratum 2)	85 Percentage of Participants Interval 70.8 to 98.5	79 Percentage of Participants Interval 63.4 to 93.8	82 Percentage of Participants Interval 71.1 to 91.8
The Percentage of Subjects Who Completed the 14-day Double-blind Phase. Overall	87 Percentage of Participants Interval 80.0 to 93.5	82 Percentage of Participants Interval 74.5 to 89.5	84 Percentage of Participants Interval 79.3 to 89.4

Adverse Events

Double-blind BTDS 10/20

Serious events: 2 serious events

Other events: 31 other events

Deaths: 0 deaths

Double-blind BTDS 20

Serious events: 3 serious events

Other events: 47 other events

Deaths: 0 deaths

Open-label Run-in Period - Vicodin

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Double-blind BTDS 10/20 n=101 participants at risk Initial doses (Level 1) of BTDS 10. Subjects were allowed to have their dose adjusted to BTDS 20 (Level 2) on or after day 4. Subjects remained on their treatment regimen until day 14 (± 2 days) or until they discontinued from the study. Downward titration was not permitted.	Double-blind BTDS 20 n=103 participants at risk Initial doses (Level 1) of BTDS 20. Subjects remained on their treatment regimen until day 14 (± 2 days) or until they discontinued from the study. Downward titration was not permitted.	Open-label Run-in Period - Vicodin n=266 participants at risk N = 266 subjects received a stable regimen of Vicodin® in the Run-in period and were eligible for randomization if they reported a daily "average pain over the last 24 hours" score of 0 = none or 1 = mild on at least 5 of the 7 days; and used ≤ 2 doses of supplemental analgesic per day for their osteoarthritic (OA) pain. N = 204 completed the run-in.
Infections and infestations Creutzfeldt-Jacob disease - DEATH	0.00% 0/101 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.97% 1/103 • Number of events 1 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.00% 0/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.
Psychiatric disorders Exacerbation of anxiety disorder	0.99% 1/101 • Number of events 1 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.00% 0/103 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.00% 0/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.
Nervous system disorders Headache	0.00% 0/101 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.97% 1/103 • Number of events 1 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.00% 0/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.
Vascular disorders Increased hypertension	0.00% 0/101 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.97% 1/103 • Number of events 1 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.00% 0/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.
Musculoskeletal and connective tissue disorders Leg pain	0.00% 0/101 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.97% 1/103 • Number of events 1 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.00% 0/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.
Musculoskeletal and connective tissue disorders Myositis	0.00% 0/101 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.97% 1/103 • Number of events 1 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.00% 0/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.
Skin and subcutaneous tissue disorders Rash NOS, Chest, Arms, Face	2.0% 2/101 • Number of events 2 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.00% 0/103 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.00% 0/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.
Skin and subcutaneous tissue disorders Rash generalized	0.99% 1/101 • Number of events 1 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.00% 0/103 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.00% 0/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.

Other adverse events

Other adverse events
Measure	Double-blind BTDS 10/20 n=101 participants at risk Initial doses (Level 1) of BTDS 10. Subjects were allowed to have their dose adjusted to BTDS 20 (Level 2) on or after day 4. Subjects remained on their treatment regimen until day 14 (± 2 days) or until they discontinued from the study. Downward titration was not permitted.	Double-blind BTDS 20 n=103 participants at risk Initial doses (Level 1) of BTDS 20. Subjects remained on their treatment regimen until day 14 (± 2 days) or until they discontinued from the study. Downward titration was not permitted.	Open-label Run-in Period - Vicodin n=266 participants at risk N = 266 subjects received a stable regimen of Vicodin® in the Run-in period and were eligible for randomization if they reported a daily "average pain over the last 24 hours" score of 0 = none or 1 = mild on at least 5 of the 7 days; and used ≤ 2 doses of supplemental analgesic per day for their osteoarthritic (OA) pain. N = 204 completed the run-in.
General disorders Application site erythema	6.9% 7/101 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	6.8% 7/103 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.00% 0/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.
General disorders Application site pruritus	10.9% 11/101 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	17.5% 18/103 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.00% 0/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.
Musculoskeletal and connective tissue disorders Arthralgia	2.0% 2/101 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	7.8% 8/103 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.00% 0/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.
Nervous system disorders Dizziness	3.0% 3/101 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	6.8% 7/103 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.38% 1/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.
Nervous system disorders Headache	8.9% 9/101 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	8.7% 9/103 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	2.3% 6/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.
Gastrointestinal disorders Nausea	9.9% 10/101 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	9.7% 10/103 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	1.5% 4/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.
Nervous system disorders Somnolence	6.9% 7/101 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	8.7% 9/103 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	0.38% 1/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.
Gastrointestinal disorders Vomiting NOS	5.9% 6/101 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	6.8% 7/103 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.	1.1% 3/266 • Adverse events (AEs) that occurred after the signing of the informed consent up to end of study and followed until resolution or 30 days after the last dose of study drug, or discontinuation; serious AEs were followed until the AE stabilized AEs were learned of through spontaneous reports and subject interview.

Additional Information

Clinical Leader

Purdue Pharma L.P.

Phone: 800-733-1333

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60