Safety of Buprenorphine Transdermal Patch (BTDS) in Osteoarthritis Pain: a 52-Week Extension Phase

• Sponsor: Purdue Pharma LP (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01135524
• Collaborator: (none)
• Enrollment: 196
• Locations: 89
• Arm: 1
• Duration (Months): 16
• Patients Per Site: 2.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this phase is to evaluate the long-term safety and tolerability of BTDS. Qualified subjects are started on BTDS 5 and the dose may be titrated, if necessary, to a maximum of BTDS 20 to achieve stable pain control.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis	Drug: Buprenorphine transdermal patch; Drug: Buprenorphine transdermal patch; Drug: Buprenorphine transdermal patch	Phase 3

Detailed Description

Buprenorphine is a synthetic opioid analgesic with over 25 years of international clinical experience indicating it to be safe and effective in a variety of therapeutic situations for the relief of moderate to severe pain.

Study Design

• Study Type: Interventional
• Actual Enrollment: 196 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Multicenter, Active Comparator Study to Determine the Efficacy and Safety of BTDS 20 or OxyIR® Versus BTDS 5 in Subjects With Moderate to Severe Osteoarthritis (OA) Pain: A 52-Week Extension Phase
• Study Start Date: Apr 1, 2004
• Actual Primary Completion Date: Aug 1, 2005
• Actual Study Completion Date: Aug 1, 2005

Arms and Interventions

Arm

Intervention/Treatment

Experimental: BTDS Buprenorphine transdermal patch

Drug: Buprenorphine transdermal patch; Buprenorphine transdermal patch 5 mcg/h applied transdermally for 7-day wear.; Other Names: Butrans™ ; Drug: Buprenorphine transdermal patch; Buprenorphine transdermal patch 10 mcg/h applied transdermally for 7-day wear.; Other Names: Butrans™ ; Drug: Buprenorphine transdermal patch; Buprenorphine transdermal patch 20 mcg/h applied transdermally for 7-day wear.; Other Names: Butrans™

Outcome Measures

Primary Outcome Measures

1. The Number of Participants With Adverse Events as a Measure of Safety and Tolerability [52 weeks]

   Safety was assessed using reports of adverse events, clinical laboratory results, findings from physical examinations, and vital sign measurements.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects who completed all visits of the double-blind phase on study drug and subjects who discontinued study drug due to lack of therapeutic effect in the double-blind phase but completed all visits of the double-blind phase off study drug are eligible to enroll in the extension phase.

Exclusion Criteria:

• Subjects who prematurely discontinue study drug in the double-blind phase due to adverse event, subject's choice, administrative reason or lost to follow-up are NOT eligible to enter the extension phase

• Subjects with electrocardiograms (ECGs) that show any QT data corrected for heart rate using Fridericia formula (QTcF) interval ≥ 500 millisecond (msec) will be discontinued from the extension phase.

• Subjects requiring long-acting opioid analgesics (once- or twice-daily dosing with an every (q) 24 hour (h) or q12h drug) or transdermal fentanyl during the extension phase should be discontinued from the study.

Refer to core study for additional inclusion/exclusion information.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Neurology and Pain Medicine	Alabaster	Alabama	United States	35007
2	Research Facility	Birmingham	Alabama	United States	35215
3	The Birmingham Pain Center	Birmingham	Alabama	United States	35244
4	University of Alabama Hospital	Birmingham	Alabama	United States	35249
5	HealthSouth Metro West Hospital	Fairfield	Alabama	United States	35064
6	Research Facility	Phoenix	Arizona	United States	85018
7	Arizona Research Center	Phoenix	Arizona	United States	85023
8	Research Facility	Phoenix	Arizona	United States	85029
9	Research Facility	Tucson	Arizona	United States	85712
10	Hot Springs Pain Clinic	Hot Springs	Arkansas	United States	71913
11	Research Facility	Buena Park	California	United States	90620
12	Research Facility	Chula Vista	California	United States	91911
13	Research Facility	Fresno	California	United States	93720
14	Research Facility	Los Gatos	California	United States	95032
15	Research Facility	Roseville	California	United States	95661
16	NTOUCH Research Corporation	San Diego	California	United States	92103
17	Research Facility	San Diego	California	United States	92120
18	Research Facility	Torrence	California	United States	90505
19	Research Facility	Upland	California	United States	91786
20	Research Facility	Pueblo	Colorado	United States	81008
21	Research Facility	Bridgeport	Connecticut	United States	06606
22	Research Facility	Coral Gables	Florida	United States	33134
23	Research Facility	Daytona Beach	Florida	United States	32114
24	Research Facility	Hialeah	Florida	United States	33013
25	Research Facility	Jupiter	Florida	United States	99458
26	Research Facility	Largo	Florida	United States	33770
27	Research Facility	Miami	Florida	United States	33155
28	Research Facility	North Miami Beach	Florida	United States	33180
29	Research Facility	Ocala	Florida	United States	34471
30	Research Facility	Ormond Beach	Florida	United States	32174
31	Research Facility	Palm Harbor	Florida	United States	34684
32	Research Facility	Pembroke Pines	Florida	United States	33024
33	Radiant Research	Pinellas Park	Florida	United States	33781
34	Research Facility	Plantation	Florida	United States	33324
35	Research Facility	Port Orange	Florida	United States	32127
36	Research Facility	Tampa	Florida	United States	33614
37	Research Facility	West Palm Beach	Florida	United States	33409
38	Research Facility	Marietta	Georgia	United States	30060
39	Research Facility	Boise	Idaho	United States	83702
40	Idaho Arthritis Osteoporosis	Meridian	Idaho	United States	83642
41	Research Facility	Chicago	Illinois	United States	60610
42	Research Facility	Springfield	Illinois	United States	62704
43	Integrated Clinical Trials	West Des Moines	Iowa	United States	50265
44	Louisville Endocrinology PSC	Louisville	Kentucky	United States	40213
45	Research Facility	Madisonville	Kentucky	United States	42431
46	Research Facility	New Orleans	Louisiana	United States	70114
47	Research Facility	New Orleans	Louisiana	United States	70115
48	Dolby Providers	New Orleans	Louisiana	United States	70128
49	Research Facility	Baltimore	Maryland	United States	21215
50	Patuxent Medical Group	Columbia	Maryland	United States	21045
51	Research Facility	Hagerstown	Maryland	United States	21740
52	Research Facility	Brockton	Massachusetts	United States	02301
53	Crystal Lake Health Center	Benzonia	Michigan	United States	49616
54	Rheumatology PC	Kalamazoo	Michigan	United States	49009
55	Research Facility	Lansing	Michigan	United States	48917
56	KC Pain Centers East	Independence	Missouri	United States	64055
57	Research Facility	St. Louis	Missouri	United States	63117
58	HealthCare Research LLC	St. Louis	Missouri	United States	63141
59	Research Facility	Las Vegas	Nevada	United States	89106
60	Research Facility	Las Vegas	Nevada	United States	89117
61	Research Facility	New York	New York	United States	10021
62	Research Facility	Syracuse	New York	United States	13210
63	The Arthritis Clinic and Carolina Bone and Joint	Charlotte	North Carolina	United States	28210
64	Triangle Orthopaedic Associates	Durham	North Carolina	United States	27704
65	Research Facility	Greensboro	North Carolina	United States	27401
66	Research Facility	Hickory	North Carolina	United States	28601
67	Cornerstone Research Care	High Point	North Carolina	United States	27262
68	Research Facility	Cincinnati	Ohio	United States	45241
69	Research Facility	Columbus	Ohio	United States	43235
70	Research Facility	Oklahoma City	Oklahoma	United States	73103
71	Research Facility	Eugene	Oregon	United States	97404
72	Research Facility	Altoona	Pennsylvania	United States	16602
73	Research Facility	Duncansville	Pennsylvania	United States	16635
74	The Clinical Trial Center	Jenkintown	Pennsylvania	United States	19046
75	Research Facility	Mechanicsburg	Pennsylvania	United States	17055
76	New England Center for Clinical Research	Cranston	Rhode Island	United States	02920
77	Radiant Research	Greer	South Carolina	United States	29651
78	Allergy ARTS	Amarillo	Texas	United States	79124
79	Research Facility	Conroe	Texas	United States	77304
80	Family Practice Associates	Corpus Christi	Texas	United States	78411
81	Research Facility	Dallas	Texas	United States	75218
82	Research Facility	Dallas	Texas	United States	75251
83	Research Facility	Houston	Texas	United States	77054
84	KRK Medical Research	Richardson	Texas	United States	75080
85	Research Facility	San Antonio	Texas	United States	78217
86	Research Facility	San Antonio	Texas	United States	78238
87	Research Facility	Spokane	Washington	United States	99207
88	Research Facility	Milwaukee	Wisconsin	United States	53218
89	Research Facility	New Berlin	Wisconsin	United States	53151

Sponsors and Collaborators

• Purdue Pharma LP

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Product Information

Publications

None provided.

• Responsible Party: Purdue Pharma LP
• ClinicalTrials.gov Identifier: NCT01135524
• Other Study ID Numbers: BUP3019S
• First Posted: Jun 2, 2010
• Last Update Posted: Sep 10, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by Purdue Pharma LP: Osteoarthritis; Opioid; Transdermal
• Additional relevant MeSH terms: Osteoarthritis; Buprenorphine

Study Results

Participant Flow

Recruitment Details	02-Apr-2004 (first subject first visit, core study) to 05-Aug-2005 (last subject last visit, extension phase), in 82 sites in the US; 59 sites randomized at least 1 subject.
Pre-assignment Detail	Subjects with moderate to severe osteoarthritis (OA) pain who required opioid analgesia; completed all visits of the double-blind phase on study drug, or who discontinued study drug due to lack of therapeutic effect in the double-blind phase and completed all visits of the double-blind phase off study drug were eligible for the extension phase.

Arm/Group Title	Extension Phase
Arm/Group Description	Open-label buprenorphine transdermal patch 5, 10, 20 mcg/h applied for 7-day wear
Period Title: Overall Study
STARTED	196
COMPLETED	0
NOT COMPLETED	196

Baseline Characteristics

Arm/Group Title	Extension Phase
Arm/Group Description	Open-label buprenorphine transdermal patch 5, 10, 20 mcg/h applied for 7-day wear
Overall Participants	196
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.4 (9.83)
Sex: Female, Male (Count of Participants)
Female	150 76.5%
Male	46 23.5%

Outcome Measures

1. Primary Outcome

Title	The Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Description	Safety was assessed using reports of adverse events, clinical laboratory results, findings from physical examinations, and vital sign measurements.
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

The Extension Safety Population (N = 196) consisted of all subjects who received at least 1 dose of the open-label BTDS extension study drug, and had at least 1 safety assessment during the extension phase.

Arm/Group Title	Extension Phase
Arm/Group Description	Open-label buprenorphine transdermal patch 5, 10, 20 mcg/h applied for 7-day wear
Measure Participants	196
Deaths	1 0.5%
Serious Adverse Events	14 7.1%
Other Adverse Events in ≥ 4.5% of subjects	93 47.4%

Adverse Events

Time Frame	Extension phase: AEs occurring after the application of the first patch during the extension phase were recorded up to 7 days after the last visit; serious AEs up to 30 days following the last study visit were followed until the event resolved.
Adverse Event Reporting Description	AEs were obtained through spontaneous reports and subject interview.
Arm/Group Title	Extension Phase
Arm/Group Description	Open-label buprenorphine transdermal patch 5, 10, 20 mcg/h applied for 7-day wear
All Cause Mortality
	Extension Phase
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Extension Phase
	Affected / at Risk (%)	# Events
Total	14/196 (7.1%)
Cardiac disorders
Mild myocardial infarction	1/196 (0.5%)	1
Myocardial infarction	1/196 (0.5%)	1
Unstable angina	1/196 (0.5%)	1
Gastrointestinal disorders
Gastroenteritis	1/196 (0.5%)	1
Rectal polyp	1/196 (0.5%)	1
Worsening hiatal hernia	1/196 (0.5%)	1
General disorders
Atypical chest pain	1/196 (0.5%)	1
Chest pain	1/196 (0.5%)	1
Withdrawal symptoms	1/196 (0.5%)	1
Investigations
Weight loss	1/196 (0.5%)	1
Musculoskeletal and connective tissue disorders
Aggravated osteoarthritis	1/196 (0.5%)	1
Herniated lumbar disc	1/196 (0.5%)	1
Worsening left hip OA	1/196 (0.5%)	1
Nervous system disorders
Cerebrovascular accident	1/196 (0.5%)	1
Worsening of lumbar stenosis	1/196 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Left lung pneumothorax	1/196 (0.5%)	1
Pulmonary embolism	1/196 (0.5%)	1
Vascular disorders
Gangrene right foot	1/196 (0.5%)	1
Other (Not Including Serious) Adverse Events
	Extension Phase
	Affected / at Risk (%)	# Events
Total	93/196 (47.4%)
Gastrointestinal disorders
Constipation	9/196 (4.6%)
Nausea	12/196 (6.1%)
General disorders
Application site erythema	11/196 (5.6%)
Application site pruritus	22/196 (11.2%)
Application site rash	20/196 (10.2%)
Pain NOS	10/196 (5.1%)
Infections and infestations
Urinary tract infection NOS	10/196 (5.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	19/196 (9.7%)
Joint swelling	9/196 (4.6%)
Pain in limb	10/196 (5.1%)
Nervous system disorders
Headache	31/196 (15.8%)

Limitations/Caveats

This study was terminated early for administrative reasons.

More Information

Certain Agreements

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

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.