Buprenorphine Transdermal System (BTDS) in Subjects w/Mod-sev Osteoarthritis (OA) Chronic Pain of Knee

• Sponsor: Purdue Pharma LP (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00531427
• Collaborator: (none)
• Enrollment: 567
• Locations: 87
• Arms: 2
• Duration (Months): 26
• Patients Per Site: 6.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The objective of this study is to determine the analgesic efficacy and safety of Buprenorphine Transdermal System (BTDS) 10 and 20 compared to placebo in opioid-naïve subjects with moderate to severe chronic pain due to osteoarthritis (OA) of the knee. The double-blind treatment intervention duration is 12 weeks, during which time supplemental analgesic medication (immediate-release oxycodone for the first 6 days postrandomization and acetaminophen or ibuprofen for the remainder of the double-blind phase) will be provided to all subjects in addition to study drug.

Condition or Disease	Intervention/Treatment	Phase
Chronic Pain; Osteoarthritis of the Knee	Drug: Buprenorphine; Drug: Placebo	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 settings for the relief of moderate to severe pain. BTDS is a transdermal system formulation that is designed to deliver a consistent and a steady dose of buprenorphine over a 7-day period with limited blood concentration fluctuation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 567 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-blind, Placebo-controlled With Open-label Run-in Assessing Efficacy, Tolerability,Safety of BTDS 10 or 20 Compared to Placebo in Opioid-naïve Subjects w/Moderate to Severe, Chronic Pain Due to OA of Knee
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Apr 1, 2009
• Actual Study Completion Date: Nov 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Buprenorphine transdermal system 10 and 20 applied for 7-day wear	Drug: Buprenorphine; transdermal system 10 and 20 applied for 7-day wear
Placebo Comparator: 2 Placebo transdermal system to match BTDS patches, applied for 7-day wear	Drug: Placebo; transdermal system (placebo) applied for 7-day wear

Outcome Measures

Primary Outcome Measures

1. "Average Pain Over the Last 24 Hours" Score of the Study Knee at Week 12 of the Double Blind Phase. [24 hours (week 12)]

   "Average pain over the last 24 hours" scores of the study knee at week 12 was evaluated on an 11-point scale: 0 = no pain, 10 = worst pain imaginable, recorded daily.

Secondary Outcome Measures

1. Mean Daily Number of Tablets of Nonopioid Supplemental Analgesic Used From Week 2 to 12 of the Double-blind Phase. [10 weeks]

   Subjects were permitted to take sponsor-provided supplemental analgesic medication after week 1 of the double-blind treatment (acetaminophen or ibuprofen).

2. Sleep Disturbance Subscale of the MOS-Sleep Scale at Weeks 4, 8, and 12 of the Double-blind Phase. [Weeks 4, 8, and 12 of the double-bind phase]

   The MOS Sleep Scale consists of 12 individual items (4 sleep disturbance, 2 sleep adequacy, 1 quantity of sleep and 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 ( 1 = 0-15 min to more than 60 min) and Questions 2 to 12 are scored on a scale of 1 to 6 (1 = all of the time to 6 = none of the time. 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:

• subjects with moderate to severe chronic osteoarthritis (OA) pain of the knee (lasting several hours daily) as their predominant pain condition,

• clinical diagnosis of OA of the knee 1 year or longer,

• subjects treated within the 14 days prior to screening with nonopioid therapy only, or with therapy including opioids at a dose of < 5 mg oxycodone (or equivalent) per day,

• subjects whose OA knee pain is not adequately controlled with nonopioid analgesic medication and who the investigator feels are appropriate candidates for around-the-clock opioid therapy.

Exclusion Criteria:

• subjects who have had arthroscopy on either knee or hip within 6 months of entering the study or open surgery on either knee or hip within 9 months of entering the study,

• subjects who are allergic to buprenorphine or who have a history of allergies to other opioids,

• subjects who have allergies or other contraindications to transdermal delivery systems or patch adhesives.

Other protocol-specific inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Coastal Clinical Research, Inc.	Mobile	Alabama	United States	36608
2	Radiant Research, Phoenix Southeast	Chandler	Arizona	United States	85225
3	Arizona Research Center, Inc.	Phoenix	Arizona	United States	85023
4	Research Facility	Phoenix	Arizona	United States	85029
5	Research Facility	Phoenix	Arizona	United States	85032
6	Research Facility	Anaheim	California	United States	92801
7	Lovelace Scientific Resources, Inc.	Beverly Hills	California	United States	90211
8	Catalina Research Institute	Chino	California	United States	91710
9	Research Facility	Downey	California	United States	90241
10	Research Facility	Foothill Ranch	California	United States	92610
11	Research Facility	Laguna Hills	California	United States	92653
12	Research Facility	Sacramento	California	United States	95831
13	Research Facility	Littleton	Colorado	United States	80128
14	Research Facility	Stamford	Connecticut	United States	06905
15	Coastal Pain Management	Bradenton	Florida	United States	34209
16	Clinical Research of West Florida	Clearwater	Florida	United States	33765
17	Research Facility	Clearwater	Florida	United States	33765
18	Research Facility	Jupiter	Florida	United States	33458-7200
19	Research Facility	Largo	Florida	United States	33765
20	Pharmax Research Clinic	Miami	Florida	United States	33126
21	Research Facility	Miami	Florida	United States	33135
22	Research Facility	Orlando	Florida	United States	32806
23	Research Facility	Plantation	Florida	United States	33324
24	Research Facility	Royal Palm	Florida	United States	33411
25	Clinical Research of West Flor	Tampa	Florida	United States	33603
26	Research Facility	Tampa	Florida	United States	33613
27	Research Facility	Venice	Florida	United States	34292
28	Research Facility	West Palm Beach	Florida	United States	33409
29	Research Facility	Atlanta	Georgia	United States	30342
30	Research Facility	Augusta	Georgia	United States	30901
31	AMR Research Associates	Bogart	Georgia	United States	30622-6821
32	Research Facility	Dawsonville	Georgia	United States	30534
33	Research Facility	Decatur	Georgia	United States	30033
34	Research Facility	Marietta	Georgia	United States	30066
35	Research Facility	Honolulu	Hawaii	United States	96814-4526
36	Rehabilitation Association of IN	Indianapolis	Indiana	United States	46250
37	Research Facility	Overland Park	Kansas	United States	66211
38	Graves-Gilbert Clinic	Bowling Green	Kentucky	United States	42101
39	Stat-Lab I, Inc.	Baton Rouge	Louisiana	United States	70808
40	Research Facility	New Iberia	Louisiana	United States	70563
41	Research Facility	New Orleans	Louisiana	United States	70114
42	Research Facility	Frederick	Maryland	United States	21702
43	Research Facility	Brockton	Massachusetts	United States	02301
44	East Coast Clinical Research	Haverhill	Massachusetts	United States	01830-6141
45	Research Facility	Springfield	Massachusetts	United States	01103
46	Research Facility	Bay City	Michigan	United States	48706
47	Premier Internal Medicine	Biloxi	Mississippi	United States	39531
48	Research Facility	Florissant	Missouri	United States	63031
49	Research Facility	St. Louis	Missouri	United States	63117
50	Sports Med Consultants PC	St. Louis	Missouri	United States	63141
51	Research Facility	Henderson	Nevada	United States	89014
52	Research Facility	New York	New York	United States	10004
53	Research Facility	New York	New York	United States	10022
54	Research Facility	Morgantown	North Carolina	United States	28655
55	Research Facility	Winston-Salem	North Carolina	United States	27103
56	Research Facility	Canton	Ohio	United States	44718
57	Research Facility	Cincinnati	Ohio	United States	45242
58	Research Facility	Columbus	Ohio	United States	43213
59	Research Facility	Columbus	Ohio	United States	43235
60	Digestive Endoscopy Center	Dayton	Ohio	United States	45415
61	Research Facility	Dayton	Ohio	United States	45432
62	Research Facility	Middleburg Heights	Ohio	United States	44130
63	Research Facility	Mt. Gilead	Ohio	United States	43338
64	Research Facility	Toledo	Ohio	United States	43623
65	Research Facility	Oklahoma City	Oklahoma	United States	73109
66	Research Facility	Eugene	Oregon	United States	97404
67	Research Facility	Medford	Oregon	United States	97504-8311
68	Paramount Clinical Research	Bridgeville	Pennsylvania	United States	15017
69	Research Facility	Duncansville	Pennsylvania	United States	16635
70	Oyster Point Family Health Ctr	Lancaster	Pennsylvania	United States	17601
71	Research Facility	Mechanicsburg	Pennsylvania	United States	17055
72	Research Facility	West Reading	Pennsylvania	United States	19611
73	New England Center for Clinical Research	Cranston	Rhode Island	United States	02920
74	Research Facility	Cranston	Rhode Island	United States	02920
75	Greenville Pharmaceutical Research	Greenville	South Carolina	United States	29415
76	Arthritis Clinic, PLLC	Jackson	Tennessee	United States	38305
77	Research Facility	Austin	Texas	United States	78756
78	Research Facility	Colleyville	Texas	United States	76034
79	Research Facility	Dallas	Texas	United States	75230
80	Research Facility	Nederland	Texas	United States	77627
81	Research Facility	San Antonio	Texas	United States	78205-1116
82	Research Facility	San Antonio	Texas	United States	78229
83	Research Facility	Sugarland	Texas	United States	77479
84	Research Facility	Salt Lake City	Utah	United States	84102
85	NDC Medical Center	Norfolk	Virginia	United States	23502
86	Independence Family Medicine	Virginia Beach	Virginia	United States	23455
87	Pacific Northwest Primary Care	Tacoma	Washington	United States	98405

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: NCT00531427
• Other Study ID Numbers: BUP3025
• First Posted: Sep 18, 2007
• Last Update Posted: Sep 10, 2012
• Last Verified: Sep 1, 2012

• Keywords provided by Purdue Pharma LP: Chronic pain,; OA of the knee,; opioid,; transdermal
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Chronic Pain; Buprenorphine

Study Results

Participant Flow

Recruitment Details	27-Sep-2007 (first patient first visit) to 28-Apr-2009 (last patient last visit) at 83 medical/research sites in US
Pre-assignment Detail	Open-label run-in period designed to select those subjects who both tolerated and responded to treatment with BTDS 10 or BTDS 20 (an enriched design). N = 1151 entered the run-in period, and N = 571 completed. One subject was not dosed, therefore N = 570 randomized. N = 3 subjects did not have safety data, therefore N = 567 had double-blind data.

Arm/Group Title	Double-blind BTDS 10 or 20	Double-blind Placebo
Arm/Group Description	Buprenorphine transdermal patches (BTDS) 10 or 20 mcg/h applied for 7-day wear	Placebo patches to match the BTDS patches applied for 7-day wear
Period Title: Overall Study
STARTED	282	285
COMPLETED	209	191
NOT COMPLETED	73	94

Baseline Characteristics

Arm/Group Title	Double-blind BTDS 10 or 20	Double-blind Placebo	Total
Arm/Group Description	Buprenorphine transdermal patches (BTDS) 10 or 20 mcg/h applied for 7-day wear	Placebo patches to match the BTDS patches applied for 7-day wear	Total of all reporting groups
Overall Participants	282	285	567
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.1 (9.75)	59.1 (9.77)	59.1 (9.75)
Sex: Female, Male (Count of Participants)
Female	175 62.1%	181 63.5%	356 62.8%
Male	107 37.9%	104 36.5%	211 37.2%

Outcome Measures

1. Primary Outcome

Title	"Average Pain Over the Last 24 Hours" Score of the Study Knee at Week 12 of the Double Blind Phase.
Description	"Average pain over the last 24 hours" scores of the study knee at week 12 was evaluated on an 11-point scale: 0 = no pain, 10 = worst pain imaginable, recorded daily.
Time Frame	24 hours (week 12)

Outcome Measure Data

Analysis Population Description

The full analysis population is the group of subjects who were randomized and received at least 1 dose of double-blind study drug

Arm/Group Title	Double-blind BTDS 10 or 20	Double-blind Placebo
Arm/Group Description	Buprenorphine transdermal patches (BTDS) 10 or 20 mcg/h applied for 7-day wear	Placebo patches to match the BTDS patches applied for 7-day wear
Measure Participants	283	287
Screening (Visit 2)	7.16 (1.340)	7.06 (1.300)
Prerandomization (Visit 3)	2.63 (1.292)	2.74 (1.186)
Double-blind Week 12 (Visit 8)	3.82 (2.644)	4.22 (2.644)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind BTDS 10 or 20, Double-blind Placebo
	Comments	[Week 12 analysis] The null hypothesis was "no group differences." The alternative hypothesis was that BTDS arm was superior to the placebo arm. Pain scale is 11 points (0 = no pain to 10 = pain as bad as you can imagine).
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0853
	Comments
	Method	Mixed Models Analysis
	Comments	Statistics are based on a mixed effect general linear model
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 95%; -0.80 to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Mean Daily Number of Tablets of Nonopioid Supplemental Analgesic Used From Week 2 to 12 of the Double-blind Phase.
Description	Subjects were permitted to take sponsor-provided supplemental analgesic medication after week 1 of the double-blind treatment (acetaminophen or ibuprofen).
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

Subjects in the full analysis population who took at least 1 dose of supplemental analgesic medication.

Arm/Group Title	Double-blind BTDS 10 or 20	Double-blind Placebo
Arm/Group Description	Buprenorphine transdermal patches (BTDS) 10 or 20 mcg/h applied for 7-day wear	Placebo patches to match the BTDS patches applied for 7-day wear
Measure Participants	136	154
Mean (Standard Deviation) [tablets]	0.701 (0.8139)	0.740 (0.8566)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind BTDS 10 or 20, Double-blind Placebo
	Comments	Categorical analysis P value is based on a Fisher's exact test. Mean daily number of tablets for subjects who took <=1 dose of supplemental analgesia
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7098
	Comments	To control multiplicity and family-wise error rate, a gate-keeping strategy (stepwise approach) was used to evaluate the statistical significance of the secondary variables. If the primary is negative, the secondary P values are descriptive only.
	Method	ANCOVA
	Comments	with treatment as a factor and screening and pre-randomization mean pain as covariates.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.037
	Confidence Interval	(2-Sided) 95%; -0.233 to 0.159
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Sleep Disturbance Subscale of the 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 sleep and 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 ( 1 = 0-15 min to more than 60 min) and Questions 2 to 12 are scored on a scale of 1 to 6 (1 = all of the time to 6 = none of the time. 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-bind phase

Outcome Measure Data

Analysis Population Description

Full Analysis Population (N = 570) consisted of subjects who were randomized and received at least 1 dose of double-blind study drug.

Arm/Group Title	Double-blind BTDS 10 or 20	Double-blind Placebo
Arm/Group Description	Buprenorphine transdermal patches (BTDS) 10 or 20 mcg/h applied for 7-day wear	Placebo patches to match the BTDS patches applied for 7-day wear
Measure Participants	283	287
Screening	49.51 (24.790)	51.23 (25.945)
Prerandomization	23.23 (19.583)	26.04 (20.822)
Week 4	27.22 (23.086)	35.08 (25.565)
Week 8	27.46 (23.795)	34.78 (24.715)
Week 12	29.60 (25.177)	33.63 (25.606)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Double-blind BTDS 10 or 20, Double-blind Placebo
	Comments	Weeks 4, 8, 12 analysis The sleep disturbance subscale was analyzed using the mixed effect linear model with fixed effects for treatment (BTDS or placebo) and time (weeks 1, 2, 4, 8, 12) as categorical, screening mean and prerandomization mean value as covariates, and subject as a random effect.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0034
	Comments	To control multiplicity and family-wise error rate, a gate-keeping strategy (stepwise approach) was used to evaluate the statistical significance of the secondary variables. If the primary is negative, the secondary P values are descriptive only.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.46
	Confidence Interval	(2-Sided) 95%; -7.44 to -1.48
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse Events (AEs) that occurred after the signing of the informed consent up to end of study and 7 days after discontinuation; or Serious AEs occurring up to 30 days following the last study visit were followed until resolution or for up to 30 days.
Adverse Event Reporting Description	AEs were obtained through spontaneous reports and subject interview.
Arm/Group Title	Double-blind BTDS		Double-blind Placebo		Open-label Run-in Period
Arm/Group Description	Buprenorphine transdermal patches (BTDS) 10 or 20 mcg/h applied for 7-day wear		Placebo patches to match the BTDS patches applied for 7-day wear		The open-label run-in period was designed with duration of time sufficient to select those subjects who both tolerated and responded to treatment with BTDS 10 or BTDS 20 (an enriched design). During this period, subjects were required to discontinue use of all nonstudy drugs used for the treatment of chronic pain and no supplemental analgesic medications were allowed. Subjects who did not tolerate BTDS 5 were discontinued from the study.
All Cause Mortality
	Double-blind BTDS		Double-blind Placebo		Open-label Run-in Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Double-blind BTDS		Double-blind Placebo		Open-label Run-in Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/282 (4.6%)		3/285 (1.1%)		5/1151 (0.4%)
Cardiac disorders
Arteriosclerosis coronary artery - DEATH	0/282 (0%)	0	0/285 (0%)	0	1/1151 (0.1%)	1
Atrial fibrillation	1/282 (0.4%)	1	1/285 (0.4%)	1	0/1151 (0%)	0
Atrial flutter	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Bradycardia	2/282 (0.7%)	2	0/285 (0%)	0	0/1151 (0%)	0
Coronary artery disease	2/282 (0.7%)	2	0/285 (0%)	0	0/1151 (0%)	0
Coronary artery stenosis	0/282 (0%)	0	1/285 (0.4%)	1	0/1151 (0%)	0
Hypertensive heart disease - DEATH	0/282 (0%)	0	0/285 (0%)	0	1/1151 (0.1%)	1
Myocardial infarction	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Acute myocardial infarction	1/282 (0.4%)	1	0/285 (0%)	0	1/1151 (0.1%)	1
Atrioventricular block second degree	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Ear and labyrinth disorders
Vertigo	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Gastrointestinal disorders
Vomiting	0/282 (0%)	0	1/285 (0.4%)	1	1/1151 (0.1%)	1
Abdominal pain	0/282 (0%)	0	1/285 (0.4%)	1	0/1151 (0%)	0
Nausea	0/282 (0%)	0	1/285 (0.4%)	1	0/1151 (0%)	0
General disorders
Chest pain	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Noncardiac chest pain	1/282 (0.4%)	1	0/285 (0%)	0	1/1151 (0.1%)	1
Immune system disorders
Drug hypersensitivity	0/282 (0%)	0	0/285 (0%)	0	1/1151 (0.1%)	1
Injury, poisoning and procedural complications
Cardiac procedure complications	0/282 (0%)	0	0/285 (0%)	0	1/1151 (0.1%)	1
Collapse of lung	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Fall	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Hip fracture	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Investigations
Blood pressure increased	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Small cell lung cancer metastatic	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Nervous system disorders
Dizziness	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Syncope	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Psychiatric disorders
Alcoholism	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Disorientation	0/282 (0%)	0	0/285 (0%)	0	1/1151 (0.1%)	1
Vascular disorders
Deep vein thrombosis	1/282 (0.4%)	1	0/285 (0%)	0	0/1151 (0%)	0
Other (Not Including Serious) Adverse Events
	Double-blind BTDS		Double-blind Placebo		Open-label Run-in Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	108/282 (38.3%)		53/285 (18.6%)		520/1151 (45.2%)
Gastrointestinal disorders
Nausea	34/282 (12.1%)		14/285 (4.9%)		242/1151 (21%)
Vomiting	19/282 (6.7%)		5/285 (1.8%)		90/1151 (7.8%)
Constipation	19/282 (6.7%)		2/285 (0.7%)		90/1151 (7.8%)
General disorders
Application site pruritus	31/282 (11%)		18/285 (6.3%)		96/1151 (8.3%)
Application site erythema	21/282 (7.4%)		14/285 (4.9%)		37/1151 (3.2%)
Application site rash	16/282 (5.7%)		10/285 (3.5%)		37/1151 (3.2%)
Fatigue	7/282 (2.5%)		3/285 (1.1%)		62/1151 (5.4%)
Nervous system disorders
Dizziness	7/282 (2.5%)		6/285 (2.1%)		132/1151 (11.5%)
Somnolence	10/282 (3.5%)		5/285 (1.8%)		119/1151 (10.3%)
Headache	18/282 (6.4%)		20/285 (7%)		93/1151 (8.1%)
Psychiatric disorders
Anxiety	16/282 (5.7%)		2/285 (0.7%)		12/1151 (1%)

Limitations/Caveats

[Not Specified]

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.