Long-term Safety of Once-daily Hydrocodone Bitartrate (HYD) Tablets For Moderate to Severe Chronic Nonmalignant and Nonneuropathic Pain. Includes a 24-week Extension Period.

• Sponsor: Purdue Pharma LP (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01400139
• Collaborator: (none)
• Enrollment: 922
• Locations: 98
• Arm: 1
• Duration (Months): 27
• Patients Per Site: 9.4
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The primary objective of this study is to characterize the long-term safety of Hydrocodone Bitartrate (HYD) tablets 20 to 120 mg once-daily in subjects with chronic nonmalignant and nonneuropathic pain.

Condition or Disease	Intervention/Treatment	Phase
Chronic Nonmalignant and Nonneuropathic Pain	Drug: Hydrocodone bitartrate q24h film-coated tablets	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 922 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Multicenter Study to Assess the Long -Term Safety of Hydrocodone Bitartrate (HYD) Tablets 20 to 120 mg Once-daily in Subjects With Moderate to Severe Chronic Nonmalignant and Nonneuropathic Pain
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hydrocodone bitartrate Hydrocodone bitartrate (HYD) once daily (q24h) tablets	Drug: Hydrocodone bitartrate q24h film-coated tablets; Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily; Other Names: Hysingla ER

Outcome Measures

Primary Outcome Measures

1. The Number of Participants With Adverse Events as a Measure of Safety [Up to 84 weeks]

   Safety assessments included AEs, clinical laboratory test results, vital sign measurements, ECG findings, and audiology assessments.

2. Daily "Average Pain Over the Last 24 Hours" [Core study: from start to end of maintenance period (up to 52 weeks); Extension study: from start of maintenance to end of extension (up to 76 weeks)]

   "Average pain over the last 24 hours" score (on an 11-point numerical rating scale where 0 = no pain and 10 = pain as bad as you can imagine).

Secondary Outcome Measures

1. "Pain Right Now" Score [Week 12]

   "Pain right now" scores were collected using an 11-point scale where 0 = no pain and 10 = pain as bad as you can imagine. The "pain right now" scores were only collected during the Core Study. "Pain right now" scores were not assessed during the Extension Period.

2. Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R) [Baseline and up to 52 weeks in the Core Study maintenance period, and up to 24 weeks in the Extension Period]

   The MOS Sleep-R is a brief, self-administered 12-item assessment designed to measure key aspects of sleep. It includes a sleep problems index II and 6 subscale scores - sleep disturbance, sleep adequacy, daytime somnolence, snoring, awaken short of breath or with headache, and quantity of sleep. For each individual and time of assessment, quantity of sleep was recorded as the number of hours slept per night. The number of hours it took the subject to fall asleep per night was categorized 1, 2, 3, 4, or 5 corresponding to 0 through 15, 16 through 30, 31 through 45, 46 through 60, or more than 60 minutes, respectively. The other scales were recorded as 1 = all of the time, 2 = most of the time, 3 = some of the time, 4 = a little of the time, or 5 = none of the time. A higher value indicates a better score, therefore a positive change from baseline indicates a better sleep pattern and a negative change from baseline indicates a worsening in sleep pattern.

3. Brief Pain Inventory Short Form (BPI-SF) [Up to 52 weeks in the Core Study maintenance period, and up to 24 weeks in the Extension Period]

   The BPI-SF assessed the severity of pain and interference of pain on daily functions. It consists of 9 sections denoted by Q1 to Q8 and Q9A to Q9G according to their order in the questionnaire, that measure pain location, intensity, pain treatment, and functional interference of pain on mood and every day activities. Scores ranged from 0 (none) to 10 (worst as can be). Four of the items (questions 3 to 6) assess severity of pain and 7 items (questions 9A to 9G) assess interference of pain. The pain interference subscale score was determined by calculating the mean of responses to Q9A - Q9G [Q9A (general activity), Q9B (mood),Q9C (walking), Q9D (working), Q9E (relations with others), Q9F (sleep), and Q9G (enjoyment of life)] and the severity of pain subscale score was determined by calculating the mean of responses to Q3 - Q6 [Q3 (worst pain in last 24 hours), Q4 (least pain in last 24 hours), Q5 (average pain), and Q6 ("pain right now")]. A lower score indicates lower pain.

4. Medical Outcomes Study 36-item Short Form (SF-36) [Up to 52 weeks in the Core Study maintenance period, and up to 24 weeks in the Extension Period]

   The SF-36 is a generic health survey with 36 items that measure functional health and well-being from the subject's perspective. The 36 questions are grouped into 11 sections. Some of the sections consist of multiple questions. The survey is summarized into 8 dimensions/scales: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. From the 8 health dimensions, physical component summary, and mental component summary measures are derived. Scores on each scale ranged from 0 to 100; a higher score indicates a better perception of health.

5. Patient Global Impression of Change (PGIC) [At Week 52 in the Core Study maintenance period and at Week 24 in the Extension Period]

   The PGIC is an ordinal scale of global evaluation that assesses the change in overall status relative to the start of the study. The scale has only 1 item that measures global change of overall status (improvement or worsening) by the subject on a 7-point scale (Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse.

6. Treatment Satisfaction Questionnaire (TSQ) - Part I [At Week 52 or upon early discontinuation at or before Week 4 in the Core Study maintenance period]

   The TSQ is a self-administered questionnaire that consists of 2 parts. Part I has 6 questions (Q1 to Q6) that ask the subject to rate the experience with use of the study drug in comparison to the prestudy pain medication regarding ease of use, convenience, frequency, pain control, and overall satisfaction. Each question was rated on a scale from 1 (extremely satisfied) to 6 (extremely dissatisfied): Q1=Satisfaction with study drug; Q2=Ease of study drug use to treat pain; Q3=Convenience of study drug to treat pain; Q4=Overall drug satisfaction managing pain; Q5=Satisfaction with frequency of use; Q6=Ease of planning study drug use. The number of subjects with each category (1-6) of response for each individual question (Q1-Q6) was summarized for subjects who entered the core study maintenance period and responded to each question. TSQ - Part I was not administered in the extension period.

7. Treatment Satisfaction Questionnaire (TSQ) - Part II [At Week 52 or upon early discontinuation at or before Week 4 in maintenance and at Week 24 in extension]

   The TSQ is a self-administered questionnaire that consists of 2 parts. Part II has 2 questions that measure the subject's willingness to continue the use of study drug as pain medication (Q1), and to recommend the study drug to someone else (Q2). Question 1 consists of 6 categories of response rated on a scale from 1 (very willing to continue) to 6 (very unwilling to continue): 1=Very willing to continue; 2=Willing to continue; 3=Somewhat willing to continue; 4=Somewhat unwilling to continue; 5=Unwilling to continue; 6=Very unwilling to continue. Question 2 consists of 3 categories of response: 1=yes; 2=no; 3=undecided. The number of subjects with each category of response for each individual question was summarized for subjects completing the core study maintenance period and for those enrolled in the extension period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria include:

• Male and female subjects ≥ 18 years of age with moderate to severe, chronic nonmalignant and nonneuropathic pain (lasting several hours daily) as their predominant pain condition for at least 3 months prior to the screening visit;

• Subjects deemed by the investigator/medically qualified designee (must be MD or DO) to be appropriate candidates for the protocol specified, around the clock HYD therapeutic regimen;

• Female subjects who are premenopausal or postmenopausal less than 1 year and who have not had surgical sterilization (ie, tubal ligation, partial or complete hysterectomy) must have a negative serum pregnancy test, be nonlactating, and willing to use adequate and reliable contraception throughout the study (eg, barrier with additional spermicidal foam or jelly, intra-uterine device, hormonal contraception);

• Subjects who are willing and able to be compliant with the protocol, are capable of subjective evaluation (ie pain scores), are able to read and understand questionnaires, are willing and able to use an electronic diary, and are able to read, understand, and sign the written informed consent form in English.

Exclusion Criteria include:

• Subjects taking opioid analgesic(s) equivalent to > 120 mg/day of oxycodone during the 14 days prior to the screening visit;

• Subjects who previously participated in an investigational hydrocodone study within 90 days prior to the first dose of study medication ;

• Subjects who have used any investigational medication other than hydrocodone within 30 days prior to the first dose of study drug;

• Subjects with any history of seizures (subjects with history of pediatric febrile seizures may participate in the study) or increase in intracranial pressure;

• Subjects with current uncontrolled depression or other uncontrolled psychiatric disorder (subjects with controlled depression or other psychiatric disorder must be on a stable medication for ≥ 1 month prior to the screening visit to participate in the study);

• Subjects with a history of alcohol, medication, or illicit drug abuse or addiction and/or history of opioid abuse or addiction at any time;

• Subjects with clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or indwelling pacemaker;

• Subjects with unstable respiratory disease that, in the opinion of the investigator, precludes entry into this study;

• Subjects with biliary tract disease, hypothyroidism, adrenal cortical insufficiency, or any other medical condition that, in the opinion of the investigator, is inadequately treated and precludes entry into the study;

• Subjects with history of malignancy within past 2 years, with exception of basal cell carcinoma that has been successfully treated;

• Subjects with evidence of impaired liver function upon entry into the study (laboratory test values ≥ 3 times the upper limit of the laboratory reference (normal) range (ULN) for aspartate transaminase [AST/SGOT] or alanine transaminase [ALT/SGPT], or values > 2 times the ULN for alkaline phosphatase), or total bilirubin level > 1.5 times the ULN or, in the opinion of the investigator/medically qualified designee (must be MD or DO), liver function impairment to the extent that the subject should not participate in this study;

• Subjects with evidence of impaired kidney function upon entry into the study (ie, serum creatinine ≥ 2.5 mg/dL);

• Subjects with any condition in which opioids are contraindicated, eg, severe respiratory depression with hypoxia and/or hypercapnia, severe chronic obstructive lung disease, cor pulmonale, severe bronchial asthma, or paralytic ileus;

• Subjects who are allergic to hydrocodone or who have a history of allergies to other opioids. This does not include subjects who have experienced common opioid side effects (eg, nausea, constipation);

• Subjects receiving monoamine oxidase inhibitors (MAOIs) or who have been taking MAOIs within 2 weeks of the screening visit.

Other protocol-specific inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alliance Clinical Research	Birmingham	Alabama	United States	35213
2	Arizona Research Center	Phoenix	Arizona	United States	85023
3	Genova Clinical Research	Tucson	Arizona	United States	85704
4	Quality of Life Medical & Research Center, LLC	Tucson	Arizona	United States	85712
5	ACRI -Phase1, LLC	Anaheim	California	United States	92801-2417
6	United Clinical Research Center, Inc.	Anaheim	California	United States	92804
7	Med Center	Carmichael	California	United States	95608
8	Research Center of Fresno, Inc.	Fresno	California	United States	93726
9	TriWest Research Associates	La Mesa	California	United States	91942
10	Torrance Clinical Research	Lomita	California	United States	90717
11	Skyline Research, LLC	Long Beach	California	United States	90806
12	Lotus Clinical Research, LLC	Pasadena	California	United States	91105
13	Center for Clinical Research, Inc	Richmond	California	United States	94806
14	Northern California Research	Sacramento	California	United States	95821
15	Encompass Clinical Research	Spring Valley	California	United States	91978
16	Chase Medical Research, LLC	Waterbury	Connecticut	United States	06708
17	Meridien Research	Bradenton	Florida	United States	34208
18	Innovative Research of West Florida, Inc.	Clearwater	Florida	United States	33756
19	Avail Clinical Research, LLC	DeLand	Florida	United States	32720
20	Clinical Physiology Associates	Fort Myers	Florida	United States	33916
21	MD Clinical	Hallandale Beach	Florida	United States	33009
22	AGA Clinical Trials	Hialeah	Florida	United States	33012
23	Clinical Neuroscience Solutions, Inc.	Jacksonville	Florida	United States	32216
24	Health Awareness, Inc.	Jupiter	Florida	United States	33458
25	Fidelity Clinical Research, Inc.	Lauderhill	Florida	United States	33319
26	Neuroscience Consultants LLC	Miami	Florida	United States	33176
27	Renstar Medical Research	Ocala	Florida	United States	34471
28	Compass Research, LLC	Orlando	Florida	United States	32806
29	Peninsula Research, Inc.	Ormond Beach	Florida	United States	32174
30	Gold Coast Research, LLC	Plantation	Florida	United States	33317
31	Clinical Research of West Florida, Inc.	Tampa	Florida	United States	33603
32	Southeast Regional Research Group	Columbus	Georgia	United States	31904
33	Georgia Institute for Clinical Research, LLC	Marietta	Georgia	United States	30060
34	Taylor Research, LLC	Marietta	Georgia	United States	30060
35	Atlanta Knee and Shoulder Clinic, PC	Stockbridge	Georgia	United States	30281
36	Illinois Center for Clinical Research	Chicago	Illinois	United States	60622
37	Rehabilitation Associates of Indiana	Indianapolis	Indiana	United States	46250
38	Northwest Indiana Center for Clinical Research	Valparaiso	Indiana	United States	46383
39	Integrated Clinical Trial Services, Inc.	West Des Moines	Iowa	United States	50265
40	ICRI	Leawood	Kansas	United States	66211
41	Community Research	Crestview Hills	Kentucky	United States	41017
42	Commonwealth Biomedical Research, LLC	Madisonville	Kentucky	United States	42431
43	Louisiana Research Associates, Inc.	New Orleans	Louisiana	United States	70114
44	Beacon Clinical Research, LLC	Brockton	Massachusetts	United States	02301
45	MedVadis Research Corporation	Watertown	Massachusetts	United States	02472-3930
46	Medical Research Associates, Inc.	Traverse City	Michigan	United States	49684
47	Medex Healthcare Research, Inc.	Saint Louis	Missouri	United States	63117
48	Advance Clinical Research	Saint Louis	Missouri	United States	63128
49	Mercy Health Research	Saint Louis	Missouri	United States	63141
50	Sundance Clinical Research, LLC	Saint Louis	Missouri	United States	63141
51	Quality Clinical Research	Omaha	Nebraska	United States	68114
52	Advanced Biomedical Research of America	Las Vegas	Nevada	United States	89123
53	Research Facility	Las Vegas	Nevada	United States	89144
54	Comprehensive Clinical Research	Berlin	New Jersey	United States	08009
55	CRI Worldwide LLC	Willingboro	New Jersey	United States	08046
56	Lovelace Scientific Resources	Albuquerque	New Mexico	United States	87108
57	Drug Trials America	Hartsdale	New York	United States	10530
58	Research Across America	New York	New York	United States	10022
59	The Medical Research Network, LLC	New York	New York	United States	10128
60	Finger Lakes Clinical Research	Rochester	New York	United States	14618
61	Upstate Clinical Research Associates	Williamsville	New York	United States	14221
62	PMG Research of Charlotte, LLC	Charlotte	North Carolina	United States	28209
63	PMG Research of Wilmington LLC	Wilmington	North Carolina	United States	28401
64	Clinical Trials of America, Inc.	Winston-Salem	North Carolina	United States	27103
65	The Center for Clinical Research	Winston-Salem	North Carolina	United States	27103
66	Daystar Clinical Research, Inc.	Akron	Ohio	United States	44313
67	IVA Research	Cincinnati	Ohio	United States	45245
68	Community Research	Cincinnati	Ohio	United States	45255
69	Bone Joint and Spine Surgeons, Inc.	Toledo	Ohio	United States	43623
70	Cutting Edge Research Group	Oklahoma City	Oklahoma	United States	73116
71	Allegheny Pain Management, P.C.	Altoona	Pennsylvania	United States	16602
72	Pennsylvania Research Institute	Bensalem	Pennsylvania	United States	19020
73	CRI Worldwide LLC	Philadelphia	Pennsylvania	United States	19139
74	Founders Research Corporation	Philadelphia	Pennsylvania	United States	19152
75	Tipton Medical & Diagnostic Center	Tipton	Pennsylvania	United States	16684
76	Hartwell Research Group	Anderson	South Carolina	United States	29621
77	Pain Research of Charleston	Charleston	South Carolina	United States	29406
78	Radiant Research, Inc.	Greer	South Carolina	United States	29651
79	Health Concepts	Rapid City	South Dakota	United States	57702
80	Clinical Neuroscience Solutions, Inc.	Memphis	Tennessee	United States	38119
81	Heartland Medical, PC	New Tazewell	Tennessee	United States	37825
82	HCCA Clinical Research Solutions	Smyrna	Tennessee	United States	37167
83	FutureSearch Trials of Neurology	Austin	Texas	United States	78731
84	Lovelace Scientific Resources, Inc.	Austin	Texas	United States	78758
85	KRK Medical Research	Dallas	Texas	United States	75230
86	Heights Doctor's Clinic	Houston	Texas	United States	77008
87	JVC Family Medicine	Houston	Texas	United States	77040
88	Pioneer Research Solutions, Inc.	Houston	Texas	United States	77098
89	TEAM Research of Central Texas	Killeen	Texas	United States	76543
90	R/D Clinical Research, Inc.	Lake Jackson	Texas	United States	77566
91	DCOL Center for Clinical Research	Longview	Texas	United States	75605
92	Sun Research Institute	San Antonio	Texas	United States	78215
93	Martin Diagnostic Clinic	Tomball	Texas	United States	77375
94	Aspen Clinical Research	Orem	Utah	United States	84058
95	Advanced Clinical Research	West Jordan	Utah	United States	84088
96	HypotheTest, LLC	Roanoke	Virginia	United States	24018
97	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
98	Washington Center for Pain Management	Edmonds	Washington	United States	98026

Sponsors and Collaborators

• Purdue Pharma LP

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Full Prescribing Information

Publications

None provided.

• Responsible Party: Purdue Pharma LP
• ClinicalTrials.gov Identifier: NCT01400139
• Other Study ID Numbers: HYD3003
• First Posted: Jul 22, 2011
• Last Update Posted: Mar 10, 2020
• Last Verified: Mar 1, 2020

• Keywords provided by Purdue Pharma LP: Pain; Nonmalignant pain; Nonneuropathic Pain; Opioid
• Additional relevant MeSH terms: Hydrocodone

Study Results

Participant Flow

Recruitment Details	Core study: First subject first visit: 22-July-2011; Last subject last visit: 26-August-2013. Extension period: First subject first visit: 24-April-2013; Last subject last visit of 24-February-2014. The Core and Extension studies were conducted at medical/research sites in the United States.
Pre-assignment Detail	Subjects with moderate to severe, chronic nonmalignant and non-neuropathic pain.

Arm/Group Title	Hydrocodone Bitartrate (HYD)
Arm/Group Description	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Period Title: HYD Core Study
STARTED	922
COMPLETED	410
NOT COMPLETED	512
Period Title: HYD Core Study
STARTED	106
COMPLETED	83
NOT COMPLETED	23

Baseline Characteristics

Arm/Group Title	HYD Core Study
Arm/Group Description	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Overall Participants	922
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.8 (12.53)
Sex: Female, Male (Count of Participants)
Female	526 57%
Male	396 43%
Race/Ethnicity, Customized (participants) [Number]
White	761 82.5%
Black or African American	141 15.3%
Native Hawaiian or other Pacific Islander	2 0.2%
Asian	8 0.9%
American Indian or Alaska Native	4 0.4%
Other	6 0.7%
Screening Baseline Pain Over the Last 24 Hours (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.4 (1.60)

Outcome Measures

1. Primary Outcome

Title	The Number of Participants With Adverse Events as a Measure of Safety
Description	Safety assessments included AEs, clinical laboratory test results, vital sign measurements, ECG findings, and audiology assessments.
Time Frame	Up to 84 weeks

Outcome Measure Data

Analysis Population Description

The Core Study safety population (N=922) was defined as the group of subjects who received at least 1 dose of study drug during the study. The Extension Period safety population (N=106) was the group of core study safety population subjects who entered the extension period and received at least 1 dose of study drug in the extension period.

Arm/Group Title	HYD Core Study	HYD Extension Period
Arm/Group Description	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Measure Participants	922	106
Serious adverse events	80 8.7%	6 NaN
All other adverse events in ≥ 5% of patients	586 63.6%	0 NaN

2. Primary Outcome

Title	Daily "Average Pain Over the Last 24 Hours"
Description	"Average pain over the last 24 hours" score (on an 11-point numerical rating scale where 0 = no pain and 10 = pain as bad as you can imagine).
Time Frame	Core study: from start to end of maintenance period (up to 52 weeks); Extension study: from start of maintenance to end of extension (up to 76 weeks)

Outcome Measure Data

Analysis Population Description

The Core Study population analyzed (N=727) was the group of subjects who received at least 1 dose of study drug during the maintenance period. The Extension Period population analyzed (N=106) was the group of core study safety population subjects who entered the extension period and received at least 1 dose of study drug in the extension period.

Arm/Group Title	HYD Core Study	HYD Extension Period
Arm/Group Description	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Measure Participants	727	106
Mean (Standard Deviation) [units on a scale]	3.6 (1.80)	3.8 (1.73)

3. Secondary Outcome

Title	"Pain Right Now" Score
Description	"Pain right now" scores were collected using an 11-point scale where 0 = no pain and 10 = pain as bad as you can imagine. The "pain right now" scores were only collected during the Core Study. "Pain right now" scores were not assessed during the Extension Period.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The Core Study population analyzed was the group of subjects who received at least 1 dose of study drug during the maintenance period and provided data. Data were not collected for this outcome measure during the Extension Period.

Arm/Group Title	HYD Core Study	HYD Extension Period
Arm/Group Description	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Measure Participants	723	0
Mean (Standard Error) [units on a scale]	3.46 (0.071)

4. Secondary Outcome

Title	Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R)
Description	The MOS Sleep-R is a brief, self-administered 12-item assessment designed to measure key aspects of sleep. It includes a sleep problems index II and 6 subscale scores - sleep disturbance, sleep adequacy, daytime somnolence, snoring, awaken short of breath or with headache, and quantity of sleep. For each individual and time of assessment, quantity of sleep was recorded as the number of hours slept per night. The number of hours it took the subject to fall asleep per night was categorized 1, 2, 3, 4, or 5 corresponding to 0 through 15, 16 through 30, 31 through 45, 46 through 60, or more than 60 minutes, respectively. The other scales were recorded as 1 = all of the time, 2 = most of the time, 3 = some of the time, 4 = a little of the time, or 5 = none of the time. A higher value indicates a better score, therefore a positive change from baseline indicates a better sleep pattern and a negative change from baseline indicates a worsening in sleep pattern.
Time Frame	Baseline and up to 52 weeks in the Core Study maintenance period, and up to 24 weeks in the Extension Period

Outcome Measure Data

Analysis Population Description

The Core Study population analyzed was the group of subjects who received at least 1 dose of study drug during the maintenance period and provided data. The Extension Period safety population was the group of core study safety population subjects who entered the extension and received at least 1 dose of study drug in the extension period.

Arm/Group Title	HYD Core Study	HYD Extension Period
Arm/Group Description	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Measure Participants	718	106
Change from Baseline in Sleep Disturbance	4.69 (8.276)	3.65 (7.993)
Change from Baseline in Sleep Adequacy	3.29 (8.959)	2.94 (8.264)
Change from Baseline in Daytime Somnolence	0.57 (8.469)	0.89 (8.418)
Change from Baseline in Snoring	1.28 (6.839)	1.77 (6.960)
Change from Baseline in Shortness of Breath	1.46 (9.788)	3.46 (10.109)
Change from Baseline in Quantity of Sleep	0.29 (1.413)	0.17 (1.189)
Change from Baseline in Sleep Problem Index II	4.04 (8.530)	3.70 (8.248)

5. Secondary Outcome

Title	Brief Pain Inventory Short Form (BPI-SF)
Description	The BPI-SF assessed the severity of pain and interference of pain on daily functions. It consists of 9 sections denoted by Q1 to Q8 and Q9A to Q9G according to their order in the questionnaire, that measure pain location, intensity, pain treatment, and functional interference of pain on mood and every day activities. Scores ranged from 0 (none) to 10 (worst as can be). Four of the items (questions 3 to 6) assess severity of pain and 7 items (questions 9A to 9G) assess interference of pain. The pain interference subscale score was determined by calculating the mean of responses to Q9A - Q9G [Q9A (general activity), Q9B (mood),Q9C (walking), Q9D (working), Q9E (relations with others), Q9F (sleep), and Q9G (enjoyment of life)] and the severity of pain subscale score was determined by calculating the mean of responses to Q3 - Q6 [Q3 (worst pain in last 24 hours), Q4 (least pain in last 24 hours), Q5 (average pain), and Q6 ("pain right now")]. A lower score indicates lower pain.
Time Frame	Up to 52 weeks in the Core Study maintenance period, and up to 24 weeks in the Extension Period

Outcome Measure Data

Analysis Population Description

The Core Study population analyzed was the group of subjects who received at least 1 dose of study drug during the maintenance period and provided data. The Extension Period safety population was the group of core study safety population subjects who entered the extension and received at least 1 dose of study drug in the extension period.

Arm/Group Title	HYD Core Study	HYD Extension Period
Arm/Group Description	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Measure Participants	721	106
General Activity (Q9A)	3.24 (2.205)	3.27 (2.063)
Mood (Q9B)	2.23 (2.094)	1.90 (1.825)
Walking Ability (Q9C)	3.07 (2.402)	2.98 (2.298)
Normal Work (Q9D)	3.22 (2.346)	3.21 (2.212)
Relations with Others (Q9E)	1.63 (1.934)	1.34 (1.620)
Sleep (Q9F)	2.63 (2.258)	2.43 (1.931)
Enjoyment of Life (Q9G)	2.55 (2.312)	2.23 (2.086)
BPI - Pain Interference Subscale Score	2.65 (2.011)	2.48 (1.783)
Worst Pain - Last 24 Hours (Q3)	4.52 (1.966)	4.71 (1.875)
Least Pain - Last 24 Hours (Q4)	2.88 (1.741)	2.90 (1.494)
Average Pain (Q5)	3.67 (1.703)	3.72 (1.560)
Pain Right Now (Q6)	3.39 (1.846)	3.49 (1.606)
BPI - Severity of Pain Subscale Score	3.62 (1.730)	3.71 (1.562)

6. Secondary Outcome

Title	Medical Outcomes Study 36-item Short Form (SF-36)
Description	The SF-36 is a generic health survey with 36 items that measure functional health and well-being from the subject's perspective. The 36 questions are grouped into 11 sections. Some of the sections consist of multiple questions. The survey is summarized into 8 dimensions/scales: physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, and mental health. From the 8 health dimensions, physical component summary, and mental component summary measures are derived. Scores on each scale ranged from 0 to 100; a higher score indicates a better perception of health.
Time Frame	Up to 52 weeks in the Core Study maintenance period, and up to 24 weeks in the Extension Period

Outcome Measure Data

Analysis Population Description

The Core Study population analyzed was the group of subjects who received at least 1 dose of study drug during the maintenance period and provided data. The Extension Period safety population was the group of core study safety population subjects who entered the extension period and received at least 1 dose of study drug in the extension period.

Arm/Group Title	HYD Core Study	HYD Extension Period
Arm/Group Description	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Measure Participants	717	106
Physical Functioning	40.61 (9.709)	41.93 (9.258)
Role Physical	43.27 (8.585)	43.78 (8.545)
Bodily Pain	42.54 (6.859)	43.05 (6.608)
General Health	49.28 (9.979)	49.18 (10.498)
Vitality	49.77 (9.473)	50.45 (9.109)
Social Functioning	49.44 (7.992)	50.55 (7.055)
Role Emotional	50.63 (7.570)	51.60 (7.109)
Mental Health	52.75 (8.060)	52.93 (8.199)
Physical Component Summary	40.38 (8.962)	41.04 (8.809)
Mental Component Summary	55.13 (8.638)	55.68 (8.506)

7. Secondary Outcome

Title	Patient Global Impression of Change (PGIC)
Description	The PGIC is an ordinal scale of global evaluation that assesses the change in overall status relative to the start of the study. The scale has only 1 item that measures global change of overall status (improvement or worsening) by the subject on a 7-point scale (Very much improved, Much improved, Minimally improved, No change, Minimally worse, Much worse, Very much worse.
Time Frame	At Week 52 in the Core Study maintenance period and at Week 24 in the Extension Period

Outcome Measure Data

Analysis Population Description

The Core Study population analyzed was the group of subjects who received at least 1 dose of study drug during the study. The Extension Period safety population was the group of core study safety population subjects who entered the extension period and received at least 1 dose of study drug in the extension period.

Arm/Group Title	HYD Core Study	HYD Extension Period
Arm/Group Description	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Measure Participants	773	105
Very much improved	132 14.3%	21 NaN
Much improved	276 29.9%	55 NaN
Minimally improved	164 17.8%	17 NaN
No change	121 13.1%	9 NaN
Minimally worse	47 5.1%	2 NaN
Much worse	29 3.1%	1 NaN
Very much worse	4 0.4%	0 NaN

8. Secondary Outcome

Title	Treatment Satisfaction Questionnaire (TSQ) - Part I
Description	The TSQ is a self-administered questionnaire that consists of 2 parts. Part I has 6 questions (Q1 to Q6) that ask the subject to rate the experience with use of the study drug in comparison to the prestudy pain medication regarding ease of use, convenience, frequency, pain control, and overall satisfaction. Each question was rated on a scale from 1 (extremely satisfied) to 6 (extremely dissatisfied): Q1=Satisfaction with study drug; Q2=Ease of study drug use to treat pain; Q3=Convenience of study drug to treat pain; Q4=Overall drug satisfaction managing pain; Q5=Satisfaction with frequency of use; Q6=Ease of planning study drug use. The number of subjects with each category (1-6) of response for each individual question (Q1-Q6) was summarized for subjects who entered the core study maintenance period and responded to each question. TSQ - Part I was not administered in the extension period.
Time Frame	At Week 52 or upon early discontinuation at or before Week 4 in the Core Study maintenance period

Outcome Measure Data

Analysis Population Description

The Core Study population analyzed was the group of subjects who received at least 1 dose of study drug during the maintenance period and provided data.

Arm/Group Title	HYD Core Study
Arm/Group Description	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Measure Participants	728
Q1: Satisfaction - extremely satisfied	140 15.2%
Q1: very satisfied	220 23.9%
Q1: satisfied	181 19.6%
Q1: dissatisfied	38 4.1%
Q1: very dissatisfied	8 0.9%
Q1: extremely dissatisfied	6 0.7%
Q2: Ease of study drug use - extremely easy	253 27.4%
Q2: very easy	209 22.7%
Q2: easy	110 11.9%
Q2: difficult	15 1.6%
Q2: very difficult	4 0.4%
Q2: extremely difficult	2 0.2%
Q3: Convenience of study drug-extremely convenient	266 28.9%
Q3: very convenient	196 21.3%
Q3: convenient	118 12.8%
Q3: inconvenient	8 0.9%
Q3: very inconvenient	4 0.4%
Q3: extremely inconvenient	1 0.1%
Q4: Overall drug satisfaction- extremely satisfied	141 15.3%
Q4: very satisfied	200 21.7%
Q4: satisfied	195 21.1%
Q4: dissatisfied	44 4.8%
Q4: very dissatisfied	6 0.7%
Q4: extremely dissatisfied	7 0.8%
Q5: Satisfaction use frequency-extremely satisfied	265 28.7%
Q5: very satisfied	169 18.3%
Q5: satisfied	139 15.1%
Q5: dissatisfied	14 1.5%
Q5: very dissatisfied	4 0.4%
Q5: extremely dissatisfied	2 0.2%
Q6: Ease of planning use - extremely easy	284 30.8%
Q6: very easy	189 20.5%
Q6: easy	106 11.5%
Q6: difficult	11 1.2%
Q6: very difficult	1 0.1%
Q6: extremely difficult	2 0.2%

9. Secondary Outcome

Title	Treatment Satisfaction Questionnaire (TSQ) - Part II
Description	The TSQ is a self-administered questionnaire that consists of 2 parts. Part II has 2 questions that measure the subject's willingness to continue the use of study drug as pain medication (Q1), and to recommend the study drug to someone else (Q2). Question 1 consists of 6 categories of response rated on a scale from 1 (very willing to continue) to 6 (very unwilling to continue): 1=Very willing to continue; 2=Willing to continue; 3=Somewhat willing to continue; 4=Somewhat unwilling to continue; 5=Unwilling to continue; 6=Very unwilling to continue. Question 2 consists of 3 categories of response: 1=yes; 2=no; 3=undecided. The number of subjects with each category of response for each individual question was summarized for subjects completing the core study maintenance period and for those enrolled in the extension period.
Time Frame	At Week 52 or upon early discontinuation at or before Week 4 in maintenance and at Week 24 in extension

Outcome Measure Data

Analysis Population Description

The Core Study population analyzed was the group of subjects who received at least 1 dose of study drug during the maintenance period and provided data. The Extension Period safety population was the group of core study safety population subjects who entered the extension period and received at least 1 dose of study drug in the extension period.

Arm/Group Title	HYD Core Study	HYD Extension Period
Arm/Group Description	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
Measure Participants	728	106
Q1:Willingness to continue study drug-very willing	281 30.5%	51 NaN
Q1: willing to continue	141 15.3%	29 NaN
Q1: somewhat willing to continue	53 5.7%	18 NaN
Q1: somewhat unwilling to continue	29 3.1%	4 NaN
Q1: unwilling to continue	79 8.6%	3 NaN
Q1: very unwilling to continue	53 5.7%	0 NaN
Q2: Recommend study drug for pain - yes	546 59.2%	90 NaN
Q2: no	36 3.9%	4 NaN
Q2: undecided	54 5.9%	11 NaN

Adverse Events

Time Frame	Adverse events (AEs) were reported from start of study participation through the period beyond study completion: up to 84 weeks.
Adverse Event Reporting Description	AEs were learned of through spontaneous reports and/or subject interview, or observed during physical examinations or other safety assessments. Ongoing AEs were followed until resolution or 30 days after last study drug dose. Serious AEs up to 30 days after last study drug dose or last visit were followed until AE or sequelae resolved/stabilized.
Arm/Group Title	HYD Core Study		HYD Extension Period
Arm/Group Description	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily		Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily
All Cause Mortality
	HYD Core Study		HYD Extension Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	HYD Core Study		HYD Extension Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	80/922 (8.7%)		6/106 (5.7%)
Blood and lymphatic system disorders
Anaemia	1/922 (0.1%)		0/106 (0%)
Lymphoid tissue hyperplasia	1/922 (0.1%)		0/106 (0%)
Spontaneous haematoma	1/922 (0.1%)		0/106 (0%)
Thrombotic thrombocytopenic purpura	1/922 (0.1%)		0/106 (0%)
Cardiac disorders
Acute myocardial infarction	1/922 (0.1%)		0/106 (0%)
Atrial flutter	1/922 (0.1%)		0/106 (0%)
Bradycardia	1/922 (0.1%)		0/106 (0%)
Myocardial infarction	1/922 (0.1%)		0/106 (0%)
Myocardial ischaemia	3/922 (0.3%)		0/106 (0%)
Palpitations	1/922 (0.1%)		0/106 (0%)
Supraventricular tachycardia	1/922 (0.1%)		0/106 (0%)
Tachycardia	1/922 (0.1%)		0/106 (0%)
Gastrointestinal disorders
Gastrointestinal haemorrhage	1/922 (0.1%)		0/106 (0%)
Impaired gastric emptying	1/922 (0.1%)		0/106 (0%)
Intestinal obstruction	0/922 (0%)		1/106 (0.9%)
Non-cardiac chest pain	1/922 (0.1%)		0/106 (0%)
Oesophageal obstruction	1/922 (0.1%)		0/106 (0%)
Pancreatitis	1/922 (0.1%)		0/106 (0%)
Rectal fissure	1/922 (0.1%)		0/106 (0%)
General disorders
Chest pain	5/922 (0.5%)		1/106 (0.9%)
Device dislocation	1/922 (0.1%)		0/106 (0%)
Hepatobiliary disorders
Cholelithiasis	1/922 (0.1%)		0/106 (0%)
Gallbladder cholesterolosis	1/922 (0.1%)		0/106 (0%)
Infections and infestations
Abscess limb	1/922 (0.1%)		0/106 (0%)
Appendicitis	1/922 (0.1%)		0/106 (0%)
Cellulitis staphylococcal	1/922 (0.1%)		0/106 (0%)
Clostridium difficile colitis	1/922 (0.1%)		0/106 (0%)
Diverticulitis	2/922 (0.2%)		0/106 (0%)
Gastroenteritis viral	1/922 (0.1%)		0/106 (0%)
Kidney infection	1/922 (0.1%)		0/106 (0%)
Lobar pneumonia	1/922 (0.1%)		0/106 (0%)
Necrotising fasciitis	1/922 (0.1%)		0/106 (0%)
Pneumonia	2/922 (0.2%)		1/106 (0.9%)
Pulmonary sepsis	0/922 (0%)		1/106 (0.9%)
Sinusitis	1/922 (0.1%)		0/106 (0%)
Staphylococcal infection	1/922 (0.1%)		0/106 (0%)
Tracheobronchitis	1/922 (0.1%)		0/106 (0%)
Urinary tract infection	1/922 (0.1%)		0/106 (0%)
Injury, poisoning and procedural complications
Accidental overdose	1/922 (0.1%)		0/106 (0%)
Fibula fracture	1/922 (0.1%)		0/106 (0%)
Gastrointestinal stoma complication	1/922 (0.1%)		0/106 (0%)
Muscle strain	1/922 (0.1%)		0/106 (0%)
Overdose	1/922 (0.1%)		0/106 (0%)
Pubis fracture	1/922 (0.1%)		0/106 (0%)
Spinal compression fracture	1/922 (0.1%)		0/106 (0%)
Investigations
Electrocardiogram QT prolonged	1/922 (0.1%)		0/106 (0%)
Metabolism and nutrition disorders
Diabetic ketoacidosis	1/922 (0.1%)		0/106 (0%)
Fluid overload	1/922 (0.1%)		0/106 (0%)
Metabolic acidosis	1/922 (0.1%)		0/106 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/922 (0.2%)		2/106 (1.9%)
Back pain	1/922 (0.1%)		0/106 (0%)
Osteoarthritis	4/922 (0.4%)		0/106 (0%)
Polyarthritis	1/922 (0.1%)		0/106 (0%)
Pseudoarthrosis	1/922 (0.1%)		0/106 (0%)
Rhabdomyolysis	1/922 (0.1%)		0/106 (0%)
Spinal column stenosis	1/922 (0.1%)		0/106 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/922 (0.1%)		0/106 (0%)
Malignant neoplasm progression	1/922 (0.1%)		0/106 (0%)
Pleomorphic liposarcoma	1/922 (0.1%)		0/106 (0%)
Testis cancer	1/922 (0.1%)		0/106 (0%)
Nervous system disorders
Altered state of consciousness	1/922 (0.1%)		0/106 (0%)
Carotid artery stenosis	1/922 (0.1%)		0/106 (0%)
Cauda equina syndrome	1/922 (0.1%)		0/106 (0%)
Cerebral infarction	1/922 (0.1%)		0/106 (0%)
Cerebrovascular accident	1/922 (0.1%)		0/106 (0%)
Dizziness	0/922 (0%)		1/106 (0.9%)
Intracranial aneurysm	1/922 (0.1%)		0/106 (0%)
Lethargy	1/922 (0.1%)		0/106 (0%)
Migraine	1/922 (0.1%)		0/106 (0%)
Multiple sclerosis	0/922 (0%)		1/106 (0.9%)
Nerve compression	1/922 (0.1%)		0/106 (0%)
Sedation	1/922 (0.1%)		0/106 (0%)
Syncope	1/922 (0.1%)		0/106 (0%)
Transient ischaemic attack	1/922 (0.1%)		0/106 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/922 (0.1%)		0/106 (0%)
Psychiatric disorders
Alcohol abuse	1/922 (0.1%)		0/106 (0%)
Depression	1/922 (0.1%)		0/106 (0%)
Drug abuse	5/922 (0.5%)		0/106 (0%)
Panic attack	1/922 (0.1%)		0/106 (0%)
Post-traumatic stress disorder	1/922 (0.1%)		0/106 (0%)
Substance abuse	1/922 (0.1%)		0/106 (0%)
Renal and urinary disorders
Nephrolithiasis	2/922 (0.2%)		0/106 (0%)
Renal failure acute	1/922 (0.1%)		0/106 (0%)
Urinary retention	1/922 (0.1%)		0/106 (0%)
Reproductive system and breast disorders
Breast haematoma	1/922 (0.1%)		0/106 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/922 (0%)		1/106 (0.9%)
Asthma	3/922 (0.3%)		0/106 (0%)
Bronchospasm	1/922 (0.1%)		0/106 (0%)
Chronic obstructive pulmonary disease	2/922 (0.2%)		0/106 (0%)
Dyspnoea	1/922 (0.1%)		0/106 (0%)
Emphysema	1/922 (0.1%)		0/106 (0%)
Hypercapnia	1/922 (0.1%)		0/106 (0%)
Hypoxia	1/922 (0.1%)		0/106 (0%)
Interstitial lung disease	1/922 (0.1%)		0/106 (0%)
Pulmonary artery thrombosis	1/922 (0.1%)		0/106 (0%)
Pulmonary embolism	2/922 (0.2%)		0/106 (0%)
Respiratory failure	1/922 (0.1%)		0/106 (0%)
Surgical and medical procedures
Abortion induced	1/922 (0.1%)		0/106 (0%)
Vascular disorders
Arterial occlusive disease	1/922 (0.1%)		0/106 (0%)
Deep vein thrombosis	1/922 (0.1%)		0/106 (0%)
Hypertensive crisis	1/922 (0.1%)		0/106 (0%)
Other (Not Including Serious) Adverse Events
	HYD Core Study		HYD Extension Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	586/922 (63.6%)		0/106 (0%)
Gastrointestinal disorders
Nausea	218/922 (23.6%)		0/106 (0%)
Constipation	193/922 (20.9%)		0/106 (0%)
Vomiting	100/922 (10.8%)		0/106 (0%)
Diarrhoea	56/922 (6.1%)		0/106 (0%)
General disorders
Fatigue	71/922 (7.7%)		0/106 (0%)
Infections and infestations
Upper respiratory tract infection	73/922 (7.9%)		0/106 (0%)
Sinusitis	50/922 (5.4%)		0/106 (0%)
Nasopharyngitis	47/922 (5.1%)		0/106 (0%)
Urinary tract infection	47/922 (5.1%)		0/106 (0%)
Nervous system disorders
Dizziness	106/922 (11.5%)		0/106 (0%)
Somnolence	104/922 (11.3%)		0/106 (0%)
Headache	85/922 (9.2%)		0/106 (0%)
Psychiatric disorders
Insomnia	57/922 (6.2%)		0/106 (0%)
Skin and subcutaneous tissue disorders
Pruritus	52/922 (5.6%)		0/106 (0%)

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.