Safety and Efficacy of Buprenorphine Transdermal System (BTDS) in Subjects With Moderate to Severe Osteoarthritis Pain

• Sponsor: Purdue Pharma LP (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00312221
• Collaborator: (none)
• Enrollment: 418
• Locations: 23
• Arms: 3
• Duration (Months): 16
• Patients Per Site: 18.2
• Patients Per Site Per Month: 1.1

Study Details

Study Description

Brief Summary

The objective of this study is to demonstrate the effectiveness and tolerability of the buprenorphine transdermal system (20 mg) in comparison to the buprenorphine transdermal system (5 mg) and oxycodone immediate release in subjects with moderate to severe osteoarthritis pain currently treated with oral opioids. The double-blind treatment intervention duration is 12 weeks during which time supplemental analgesic medication (acetaminophen, ibuprofen, immediate release oxycodone) will be provided to all subjects in addition to study drug.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis	Drug: Buprenorphine; Drug: Buprenorphine; Drug: oxycodone immediate-release	Phase 3

Detailed Description

Buprenorphine is a synthetic opioid analgesic with over twenty-five 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: 418 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-blind, Multicenter Study to Determine the Efficacy and Safety of BTDS 20 or Oxycodone Immediate-Release (OxyIR) Versus BTDS 5 in Subjects With Moderate to Severe Osteoarthritis (OA) Pain
• Study Start Date: Apr 1, 2004
• Actual Primary Completion Date: Jul 1, 2005
• Actual Study Completion Date: Aug 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: BTDS 5 Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear	Drug: Buprenorphine; Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear; Other Names: Butrans™
Experimental: BTDS 20 Buprenorphine transdermal patch 20 mcg/h applied for 7-day wear	Drug: Buprenorphine; Buprenorphine transdermal patch 20 mcg/h applied for 7-day wear; Other Names: Butrans™
Experimental: Oxycodone Immediate-Release (Oxy IR) 40 mg Oxycodone immediate-release 40 mg (two 5-mg capsules every 6 hours).	Drug: oxycodone immediate-release; Oxycodone immediate-release 40 mg (two 5-mg capsules every 6 hours).

Outcome Measures

Primary Outcome Measures

1. "Average Pain Over the Last 24 Hours" Scores at Weeks 4, 8, and 12 of the Double-blind Phase. [Weeks 4, 8, and 12 of the double-blind phase]

   The "average pain over the last 24 hours" score was collected using an 11-point numerical scale ranging from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. This variable was obtained at each clinic visit during the double-blind phase of the study (postrandomization weeks 1, 2, 4, 8, and 12).

Secondary Outcome Measures

1. The Mean Daily Number of Supplemental Analgesic Medication Tablets [Double-blind phase (84 days)]

   The mean daily number of supplemental analgesic medication tablets included sponsor-supplied ibuprofen, acetaminophen, or OxyIR®.

2. The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase [Weeks 4, 8 and 12 of the double-blind phase]

   The WOMAC (Version LK 3.1) measures symptoms and physical functioning of patients with OA of the hip and knee. It contains 24 items (5 pain, 2 stiffness, 17 physical function) and takes less than 5 minutes to complete. The WOMAC physical function subscale has 17 items coded as 0 to 4 (best to worst), which are summed, giving a range of 0 to 68 (best to worst).

3. The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase [Weeks 4, 8, and 12 of the Double-blind Phase]

   The MOS-Sleep Scale consists of 12 individual items: (4 sleep disturbance, 2 sleep adequacy, 1 quantity of optimal sleep, 3 somnolence, 1 snoring, and 1 shortness of breath) and takes 5 to 10 minutes to complete. Question 1 is scored on a scale of 1 to 5 and Questions 2 to 12 are scored on a scale of 1 to 6. The Sleep Disturbance Subscale score is derived from the scores to Questions 1, 3, 7 and 8, and ranges from 0 to 100, where higher scores indicate greater sleep disturbance.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Osteoarthritis of the hip, knee, or spine for 1 year or longer, confirmed by radiographic evidence within the last 2 years.

• Good pain control while on a stable dose of an opioid analgesic for osteoarthritis.

Exclusion Criteria:

• Not currently taking and tolerating opioids.

• Taking more than 80 mg per day of oral morphine sulfate or equivalent within 30 days of enrollment.

• Requiring frequent analgesic therapy for chronic condition(s), in addition to osteoarthritis.

Other protocol-specific exclusion/inclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Parkway Medical Center	Birmingham	Alabama	United States	35215
2	International Clinical Research Network	Chula Vista	California	United States	91910
3	Clinical Trials Research	Roseville	California	United States	95661
4	Accelovance	San Diego	California	United States	92108
5	Torrance Clinical Research	Torrance	California	United States	90505
6	Southern Colorado Clinic	Pueblo	Colorado	United States	81008
7	Drug Study Institute	Jupiter	Florida	United States	33458
8	Innovative Research of West Florida, Inc.	Largo	Florida	United States	33770
9	International Medical Research	Ormond Beach	Florida	United States	32174
10	Peninsula Research, Inc.	Ormond Beach	Florida	United States	32174
11	Palm Beach Research Center	West Palm Beach	Florida	United States	33409
12	Georgia Medical Research Institute	Marietta	Georgia	United States	30060
13	Non- Surgical Orthopedic & Spine Center, P.C.	Marietta	Georgia	United States	30060
14	The Arthritis Center	Springfield	Illinois	United States	62704
15	Commonwealth Biomedical Research, LLC	Madisonville	Kentucky	United States	42431
16	Miray Medical Center	Brockton	Massachusetts	United States	23010
17	Professional Clinical Research Crystal Lake Health Center	Benzonia	Michigan	United States	49616
18	Rheumatology PC	Kalamazoo	Michigan	United States	49009
19	Pharm Quest	Greensboro	North Carolina	United States	27401
20	The Clinical Trial Center, LLC	Jenkintown	Pennsylvania	United States	19046
21	Amarillo Center for Clinical Research	Amarillo	Texas	United States	79124
22	Med Search Professional Group/Pharmaceutical C-Trials Inc.	Hurst	Texas	United States	76054
23	Texas Medical Research Associates	San Antonio	Texas	United States	78238

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: NCT00312221
• Other Study ID Numbers: BUP3019
• First Posted: Apr 7, 2006
• 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; Oxycodone; Buprenorphine

Study Results

Participant Flow

Recruitment Details	Study Dates: 02-Apr-2004 (first subject first visit) to 18 Jul-2005 (last subject last visit); 15-Jun-2005 (first site notified of study termination). The study took place in 82 medical/research sites in the US; 59 sites randomized at least 1 subject.
Pre-assignment Detail	Men and women aged 40 years or older with OA of the hip, knee, or spine, on 30 to 80 mg/day morphine sulfate (MSO4) or equivalent, with or without nonopioid analgesic medication. (652 subjects entered the run-in period; 418 completed.) Subjects were eligible to enter the double-blind phase if they tolerated BTDS 20 and achieved stable analgesia.

Arm/Group Title	Run-in Period	Double-blind BTDS 5	Double-blind BTDS 20	Double-blind Oxycodone Immediate-Release
Arm/Group Description	The run-in period was designed to select subjects whose pain was adequately controlled by and who tolerated BTDS 20 treatment. BTDS 10 or 20 was applied for 7-day wear during the 3-week run-in period.	Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear	Buprenorphine transdermal patch 20 mcg/h applied for 7-day wear	Oxycodone immediate-release 40 mg (two 5-mg capsules every 6 hours).
Period Title: Open-label Run-in Period
STARTED	652	0	0	0
COMPLETED	418	0	0	0
NOT COMPLETED	234	0	0	0
Period Title: Open-label Run-in Period
STARTED	0	136	149	133
COMPLETED	0	77	77	63
NOT COMPLETED	0	59	72	70

Baseline Characteristics

Arm/Group Title	Double-blind BTDS 5	Double-blind BTDS 20	Double-blind Oxycodone Immediate-Release	Total
Arm/Group Description	Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear	Buprenorphine transdermal patch 20 mcg/h applied for 7-day wear	Oxycodone immediate-release 40 mg (two 5-mg capsules every 6 hours).	Total of all reporting groups
Overall Participants	136	149	133	418
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.7 (10.71)	57.9 (9.45)	58.1 (10.36)	58.3 (10.15)
Sex: Female, Male (Count of Participants)
Female	101 74.3%	116 77.9%	94 70.7%	311 74.4%
Male	35 25.7%	33 22.1%	39 29.3%	107 25.6%

Outcome Measures

1. Primary Outcome

Title	"Average Pain Over the Last 24 Hours" Scores at Weeks 4, 8, and 12 of the Double-blind Phase.
Description	The "average pain over the last 24 hours" score was collected using an 11-point numerical scale ranging from 0 to 10, where 0 = no pain and 10 = pain as bad as you can imagine. This variable was obtained at each clinic visit during the double-blind phase of the study (postrandomization weeks 1, 2, 4, 8, and 12).
Time Frame	Weeks 4, 8, and 12 of the double-blind phase

Outcome Measure Data

Analysis Population Description

Full Analysis Population (N = 418) consisted of subjects who were randomized and received at least 1 dose of double-blind study drug.

Arm/Group Title	Double-blind BTDS 5	Double-blind BTDS 20	Double-blind Oxycodone Immediate-Release
Arm/Group Description	Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear	Buprenorphine transdermal patch 20 mcg/h applied for 7-day wear	Oxycodone immediate-release 40 mg (two 5-mg capsules every 6 hours).
Measure Participants	136	149	133
Screening	6.60 (0.116)	6.58 (0.103)	6.44 (0.117)
Prerandomization	3.25 (0.114)	3.02 (0.093)	3.03 (0.099)
Week 4	4.21 (0.219)	3.57 (0.195)	3.45 (0.209)
Week 8	3.78 (0.239)	3.37 (0.190)	3.59 (0.217)
Week 12	3.67 (0.246)	3.56 (0.230)	3.37 (0.232)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind BTDS 5, Double-blind BTDS 20
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.126
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -0.8562 to 0.1054
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment comparison between BTDS 20 and BTDS 5 during the 12-week double-blind phase

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-blind BTDS 5, Double-blind Oxycodone Immediate-Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.140
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.36
	Confidence Interval	() 95%; -0.8455 to 0.1189
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment comparison between BTDS 5 and oxycodone immediate-release during the 12-week double-blind phase.

2. Secondary Outcome

Title	The Mean Daily Number of Supplemental Analgesic Medication Tablets
Description	The mean daily number of supplemental analgesic medication tablets included sponsor-supplied ibuprofen, acetaminophen, or OxyIR®.
Time Frame	Double-blind phase (84 days)

Outcome Measure Data

Analysis Population Description

Full Analysis Population (N = 418) consisted of subjects who were randomized and received at least 1 dose of double-blind study drug.

Arm/Group Title	Double-blind BTDS 5	Double-blind BTDS 20	Double-blind Oxycodone Immediate-Release
Arm/Group Description	Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear	Buprenorphine transdermal patch 20 mcg/h applied for 7-day wear	Oxycodone immediate-release 40 mg (two 5-mg capsules every 6 hours).
Measure Participants	136	149	133
Prerandomization	2.0 (0.19)	1.7 (0.13)	1.6 (0.13)
Double-blind	3.3 (0.26)	2.3 (0.19)	2.3 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind BTDS 5, Double-blind BTDS 20
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.47 to -0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment comparison between BTDS 5 and BTDS 20 during the 12-week double-blind phase.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-blind BTDS 5, Double-blind Oxycodone Immediate-Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.47 to -0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment comparison between BTDS 5 and oxycodone immediate-release during the 12-week double-blind phase.

3. Secondary Outcome

Title	The Physical Function Subscale of The Western Ontario and McMaster's Universities Osteoarthritis (WOMAC OA) Index at Weeks 4, 8, and 12 of the Double Blind Phase
Description	The WOMAC (Version LK 3.1) measures symptoms and physical functioning of patients with OA of the hip and knee. It contains 24 items (5 pain, 2 stiffness, 17 physical function) and takes less than 5 minutes to complete. The WOMAC physical function subscale has 17 items coded as 0 to 4 (best to worst), which are summed, giving a range of 0 to 68 (best to worst).
Time Frame	Weeks 4, 8 and 12 of the double-blind phase

Outcome Measure Data

Analysis Population Description

Full Analysis Population (N = 418) consisted of subjects who were randomized and received at least 1 dose of double-blind study drug.

Arm/Group Title	Double-blind BTDS 5	Double-blind BTDS 20	Double-blind Oxycodone Immediate-Release
Arm/Group Description	Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear	Buprenorphine transdermal patch 20 mcg/h applied for 7-day wear	Oxycodone immediate-release 40 mg (two 5-mg capsules every 6 hours).
Measure Participants	136	149	133
Screening	36.88 (1.093)	37.69 (0.930)	36.81 (1.043)
Prerandomization	25.96 (0.993)	24.19 (0.947)	24.42 (0.930)
Week 4	30.60 (1.187)	28.34 (1.025)	26.65 (1.253)
Week 8	28.70 (1.364)	28.34 (1.199)	26.59 (1.405)
Week 12	29.68 (1.500)	29.35 (1.253)	27.25 (1.651)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind BTDS 5, Double-blind BTDS 20
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.707
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -3.0054 to 2.0397
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment comparison between BTDS 5 and BTDS 20 during the 12-week double-blind phase.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-blind BTDS 5, Double-blind Oxycodone Immediate-Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.187
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.79
	Confidence Interval	(2-Sided) 95%; -4.4459 to 0.8706
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment comparison between BTDS 5 and oxycodone immediate-release during the 12-week double-blind phase.

4. Secondary Outcome

Title	The Sleep Disturbance Subscale in The Medical Outcomes (MOS)-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase
Description	The MOS-Sleep Scale consists of 12 individual items: (4 sleep disturbance, 2 sleep adequacy, 1 quantity of optimal sleep, 3 somnolence, 1 snoring, and 1 shortness of breath) and takes 5 to 10 minutes to complete. Question 1 is scored on a scale of 1 to 5 and Questions 2 to 12 are scored on a scale of 1 to 6. The Sleep Disturbance Subscale score is derived from the scores to Questions 1, 3, 7 and 8, and ranges from 0 to 100, where higher scores indicate greater sleep disturbance.
Time Frame	Weeks 4, 8, and 12 of the Double-blind Phase

Outcome Measure Data

Analysis Population Description

Full Analysis Population (N = 418) consisted of subjects who were randomized and received at least 1 dose of double-blind study drug.

Arm/Group Title	Double-blind BTDS 5	Double-blind BTDS 20	Double-blind Oxycodone Immediate-Release
Arm/Group Description	Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear	Buprenorphine transdermal patch 20 mcg/h applied for 7-day wear	Oxycodone immediate-release 40 mg (two 5-mg capsules every 6 hours).
Measure Participants	136	149	133
Screening	51.91 (2.139)	55.28 (2.035)	55.74 (2.197)
Prerandomization	34.64 (1.950)	28.65 (1.782)	33.03 (1.926)
Week 4	39.23 (2.144)	32.40 (1.941)	35.72 (2.298)
Week 8	35.95 (2.791)	31.71 (2.473)	34.13 (2.746)
Week 12	39.13 (3.089)	32.95 (2.819)	36.32 (3.290)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind BTDS 5, Double-blind BTDS 20
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.685
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.96
	Confidence Interval	(2-Sided) 95%; -5.6177 to 3.6930
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment comparison between BTDS 5 and BTDS 20 during the 12-week double-blind phase.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Double-blind BTDS 5, Double-blind Oxycodone Immediate-Release
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.443
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.81
	Confidence Interval	(2-Sided) 95%; -6.4415 to 2.8255
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment comparison between BTDS 5 and oxycodone immediate-release during the 12-week double-blind phase.

Adverse Events

Time Frame	Adverse Events (AEs) occurring after the signing of informed consent up to study completion or discontinuation; during 7 days after 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	Double-blind BTDS 5		Double-blind BTDS 20		Double-blind Oxycodone Immediate-Release		Run-in, Open-label BTDS 10 and 20
Arm/Group Description	Buprenorphine transdermal patch 5 mcg/h applied for 7-day wear during the 12-week double-blind phase		Buprenorphine transdermal patch 20 mcg/h applied for 7-day wear during the 12-week double-blind phase		Oxycodone immediate-release 40 mg (two 5-mg capsules every 6 hours) during the 12-week double-blind phase.		The run-in period was designed to select subjects whose pain was adequately controlled by and who tolerated BTDS 20 treatment. BTDS 10 or 20 was applied for 7-day wear during the 3-week run-in period.
All Cause Mortality
	Double-blind BTDS 5		Double-blind BTDS 20		Double-blind Oxycodone Immediate-Release		Run-in, Open-label BTDS 10 and 20
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Double-blind BTDS 5		Double-blind BTDS 20		Double-blind Oxycodone Immediate-Release		Run-in, Open-label BTDS 10 and 20
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/136 (2.2%)		7/149 (4.7%)		7/133 (5.3%)		8/652 (1.2%)
Cardiac disorders
Acute coronary syndrome	0/136 (0%)	0	1/149 (0.7%)	1	0/133 (0%)	0	0/652 (0%)	0
Bradycardia	0/136 (0%)	0	1/149 (0.7%)	1	0/133 (0%)	0	0/652 (0%)	0
Chest pain with ischemic episode	0/136 (0%)	0	0/149 (0%)	0	0/133 (0%)	0	1/652 (0.2%)	1
Palpitations	0/136 (0%)	0	1/149 (0.7%)	1	0/133 (0%)	0	0/652 (0%)	0
Paroxysmal supraventricular tachycardia	0/136 (0%)	0	1/149 (0.7%)	1	0/133 (0%)	0	0/652 (0%)	0
Congenital, familial and genetic disorders
Dermoid ovarian cyst	0/136 (0%)	0	0/149 (0%)	0	0/133 (0%)	0	1/652 (0.2%)	1
Gastrointestinal disorders
Acute abdomen	0/136 (0%)	0	0/149 (0%)	0	1/133 (0.8%)	1	0/652 (0%)	0
Diarrhea	0/136 (0%)	0	0/149 (0%)	0	1/133 (0.8%)	1	0/652 (0%)	0
Exacerbation of Crohn's disease	0/136 (0%)	0	1/149 (0.7%)	1	0/133 (0%)	0	0/652 (0%)	0
GI bleeding	0/136 (0%)	0	0/149 (0%)	0	1/133 (0.8%)	1	0/652 (0%)	0
Nausea	0/136 (0%)	0	0/149 (0%)	0	0/133 (0%)	0	1/652 (0.2%)	1
Vomiting	0/136 (0%)	0	0/149 (0%)	0	0/133 (0%)	0	1/652 (0.2%)	1
Acid reflux	1/136 (0.7%)	1	0/149 (0%)	0	0/133 (0%)	0	0/652 (0%)	0
General disorders
Chest pain	0/136 (0%)	0	0/149 (0%)	0	0/133 (0%)	0	1/652 (0.2%)	1
Fall	0/136 (0%)	0	1/149 (0.7%)	1	0/133 (0%)	0	0/652 (0%)	0
Fell	0/136 (0%)	0	0/149 (0%)	0	1/133 (0.8%)	1	0/652 (0%)	0
Hepatobiliary disorders
Acute cholecystitis	0/136 (0%)	0	0/149 (0%)	0	1/133 (0.8%)	1	0/652 (0%)	0
Cholelithiasis	0/136 (0%)	0	0/149 (0%)	0	0/133 (0%)	0	1/652 (0.2%)	1
Injury, poisoning and procedural complications
Fractured left hip	0/136 (0%)	0	0/149 (0%)	0	1/133 (0.8%)	1	0/652 (0%)	0
Postsurgical hip joint dislocation, left hip	0/136 (0%)	0	0/149 (0%)	0	0/133 (0%)	0	1/652 (0.2%)	1
Metabolism and nutrition disorders
Dehydration	0/136 (0%)	0	0/149 (0%)	0	1/133 (0.8%)	1	0/652 (0%)	0
Musculoskeletal and connective tissue disorders
Muscle spasms right knee	0/136 (0%)	0	0/149 (0%)	0	0/133 (0%)	0	1/652 (0.2%)	1
Recurrent L4-L5 disc herniation	0/136 (0%)	0	0/149 (0%)	0	1/133 (0.8%)	1	0/652 (0%)	0
End stage OA of the right knee	0/136 (0%)	0	1/149 (0.7%)	1	0/133 (0%)	0	0/652 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Liver cancer	1/136 (0.7%)	1	0/149 (0%)	0	0/133 (0%)	0	0/652 (0%)	0
Possible bone cancer	1/136 (0.7%)	1	0/149 (0%)	0	0/133 (0%)	0	0/652 (0%)	0
Prostatic adenocarcinoma	0/136 (0%)	0	0/149 (0%)	0	0/133 (0%)	0	1/652 (0.2%)	1
Nervous system disorders
Exacerbation of lumbar spinal stenosis	0/136 (0%)	0	1/149 (0.7%)	1	0/133 (0%)	0	0/652 (0%)	0
Recurrent L5-S1 disc herniation with impingement of the S1 nerve root	0/136 (0%)	0	0/149 (0%)	0	1/133 (0.8%)	1	0/652 (0%)	0
Transischemic attack	0/136 (0%)	0	0/149 (0%)	0	1/133 (0.8%)	1	0/652 (0%)	0
Renal and urinary disorders
Acute renal failure	0/136 (0%)	0	0/149 (0%)	0	1/133 (0.8%)	1	0/652 (0%)	0
Renal calculi	0/136 (0%)	0	1/149 (0.7%)	1	0/133 (0%)	0	0/652 (0%)	0
Reproductive system and breast disorders
Enlarged uterus	0/136 (0%)	0	0/149 (0%)	0	0/133 (0%)	0	1/652 (0.2%)	1
Metrorrhagia	0/136 (0%)	0	0/149 (0%)	0	0/133 (0%)	0	1/652 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Bronchospasm	1/136 (0.7%)	1	0/149 (0%)	0	0/133 (0%)	0	0/652 (0%)	0
Pulmonary embolism	0/136 (0%)	0	0/149 (0%)	0	0/133 (0%)	0	1/652 (0.2%)	1
Worsening asthma	1/136 (0.7%)	1	0/149 (0%)	0	0/133 (0%)	0	0/652 (0%)	0
Social circumstances
OxyIR abuse	0/136 (0%)	0	1/149 (0.7%)	1	0/133 (0%)	0	0/652 (0%)	0
Vascular disorders
Deep vein thrombosis	0/136 (0%)	0	0/149 (0%)	0	0/133 (0%)	0	1/652 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Double-blind BTDS 5		Double-blind BTDS 20		Double-blind Oxycodone Immediate-Release		Run-in, Open-label BTDS 10 and 20
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/136 (22.1%)		70/149 (47%)		56/133 (42.1%)		187/652 (28.7%)
Gastrointestinal disorders
Nausea	4/136 (2.9%)		16/149 (10.7%)		17/133 (12.8%)		94/652 (14.4%)
Constipation	3/136 (2.2%)		8/149 (5.4%)		9/133 (6.8%)		22/652 (3.4%)
Vomiting NOS	0/136 (0%)		8/149 (5.4%)		6/133 (4.5%)		32/652 (4.9%)
Abdominal pain upper	1/136 (0.7%)		0/149 (0%)		6/133 (4.5%)		1/652 (0.2%)
General disorders
Application site pruritus	13/136 (9.6%)		22/149 (14.8%)		12/133 (9%)		47/652 (7.2%)
Application site rash	5/136 (3.7%)		9/149 (6%)		8/133 (6%)		9/652 (1.4%)
Application site erythema	9/136 (6.6%)		14/149 (9.4%)		5/133 (3.8%)		9/652 (1.4%)
Pain NOS	5/136 (3.7%)		1/149 (0.7%)		7/133 (5.3%)		11/652 (1.7%)
Infections and infestations
Upper respiratory tract infection NOS	6/136 (4.4%)		6/149 (4%)		8/133 (6%)		5/652 (0.8%)
Urinary tract infection NOS	5/136 (3.7%)		8/149 (5.4%)		5/133 (3.8%)		9/652 (1.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	5/136 (3.7%)		9/149 (6%)		4/133 (3%)		12/652 (1.8%)
Pain in limb	7/136 (5.1%)		2/149 (1.3%)		3/133 (2.3%)		14/652 (2.1%)
Nervous system disorders
Headache	10/136 (7.4%)		22/149 (14.8%)		16/133 (12%)		70/652 (10.7%)
Dizziness	4/136 (2.9%)		10/149 (6.7%)		7/133 (5.3%)		43/652 (6.6%)
Somnolence	2/136 (1.5%)		2/149 (1.3%)		10/133 (7.5%)		29/652 (4.4%)

Limitations/Caveats

This study was terminated early for administrative reasons not related to safety or efficacy. Low enrollment at termination led to reduced power.

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.