Efficacy and Safety of Hydrocodone Bitartrate (HYD) in Subjects With Moderate to Severe Chronic Low Back Pain

• Sponsor: Purdue Pharma LP (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01452529
• Collaborator: (none)
• Enrollment: 905
• Locations: 102
• Arms: 2
• Duration (Months): 24
• Patients Per Site: 8.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the analgesic efficacy and safety of HYD tablets 20 to 120 mg once-daily dose compared to placebo in subjects with moderate to severe chronic low back pain uncontrolled by their current stable analgesic regimen

Condition or Disease	Intervention/Treatment	Phase
Chronic Low Back Pain	Drug: Hydrocodone bitartrate q24h film-coated tablets; Drug: Placebo to match hydrocodone bitartrate q24h tablets	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 905 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled Study With an Open-label Run-in to Assess the Efficacy and Safety of Hydrocodone Bitartrate (HYD) Tablets 20 to 120 mg Once-daily in Subjects With Moderate to Severe Chronic Low Back Pain
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Sep 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
Placebo Comparator: Placebo Placebo to match hydrocodone bitartrate once daily tablets	Drug: Placebo to match hydrocodone bitartrate q24h tablets; Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily

Outcome Measures

Primary Outcome Measures

1. Mean Pain Intensity for "Average Pain Over the Last 24 Hours" Score [Week 12]

   Mean pain intensity for "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. Medical Outcome Study Sleep Scale - Revised (MOS Sleep-R) - Sleep Disturbance Subscale [Weeks 4, 8, and 12]

   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 and 6 subscales - sleep disturbance, sleep adequacy, daytime somnolence, snoring, awaken short of breath or with headache, and quantity of sleep. The sleep disturbance subscale comprised the responses to questions 1, 3, 7, and 8 on the assessment. The individual responses for each question were recorded on a 5-point scale with options ranging from 1 - "all of the time" to 5 - "none of the time". Sleep disturbance scores were transformed linearly on a scale of 0-100. A higher value indicates a better score; therefore, a higher score indicates a better sleep pattern.

2. Patient Global Impression of Change (PGIC) [Week 12]

   The PGIC is an ordinal scale which assesses the change in overall status relative to the start of the study. The scale has only 1 item, which measures global change of overall status by the subject on a 7-point scale (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse), where 1 = very much improved and 7 = very much worse. The proportion of subjects responding "very much improved" and "much improved" was summarized by treatment group.

3. Responder Analysis for Subjects With a ≥ 30% Reduction in Pain Compared to Baseline [Baseline to Week 12]

   A subject's response to treatment was defined as the percentage reduction from the screening mean pain score to the mean pain intensity at week 12 of the double-blind period.

4. Responder Analysis for Subjects With a ≥ 50% Reduction in Pain Compared to Baseline [Baseline to Week 12]

   A subject's response to treatment was defined as the percentage reduction from the screening mean pain score to the mean pain intensity at week 12 of the double-blind 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 low back pain (lasting several hours daily) as their predominant pain condition for at least 3 months prior to the screening visit;

• Subjects whose low back pain is not adequately treated prior to the screening visit with their stable incoming analgesic regimen;

• 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).

Exclusion Criteria include:

• Subjects taking > 100 mg/day oxycodone or equivalent during last 14 days prior to screening visit;

• Subjects who cannot or will not agree to completely stop all incoming opioid and nonopioid analgesic medications and other medications used for chronic pain, excluding herbal and nutraceutical medications;

• Subjects who cannot or will not agree to stop local regional pain treatments during the study (nerve/plexus blocks or ablation, neurosurgical procedures for pain control, botulinum toxin injections for control of chronic low back pain, steroid injections in the lower back or inhalation analgesia). The subject must not have had a nerve/plexus block within 4 weeks of the screening visit, neuroablation within 6 months of the screening visit, a botulinum toxin injection in the low back region within 3 months of the screening visit, steroid injections in the lower back within 6 weeks of the screening visit, or intravenous or intramuscular steroid injections within 4 weeks of the screening visit;

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

• 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 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 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 who had surgical procedures directed towards the source of chronic low back pain within 6 months of the screening visit or scheduled for surgery of the lower back or any other major surgery during the study conduct period;

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

• 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	Coastal Clinical Research, Inc.	Mobile	Alabama	United States	36608
3	Arizona Research Center	Phoenix	Arizona	United States	85023
4	Redpoint Research	Phoenix	Arizona	United States	85029
5	Genova Clinical Research	Tucson	Arizona	United States	85704
6	Quality of Life Medical & Research Center, LLC	Tucson	Arizona	United States	85712
7	Redpoint Research	Tucson	Arizona	United States	85712
8	ACRI-Phase 1, LLC	Anaheim	California	United States	92801-2417
9	Orange County Research Institute	Anaheim	California	United States	92801
10	United Clinical Research Center, Inc.	Anaheim	California	United States	92804
11	Research Center of Fresno, Inc.	Fresno	California	United States	93726
12	TriWest Research Associates	La Mesa	California	United States	91942
13	Torrance Clinical Research Institute Inc.	Lomita	California	United States	90717
14	Skyline Research, LLC	Long Beach	California	United States	90806
15	Center for Clinical Research, Inc.	Richmond	California	United States	94806
16	Northern California Research	Sacramento	California	United States	95821
17	Encompass Clinical Research	Spring Valley	California	United States	91978
18	Chase Medical Research, LLC	Waterbury	Connecticut	United States	06708
19	Orthopedic Research Institute	Boynton Beach	Florida	United States	33472
20	Meridien Research	Bradenton	Florida	United States	34208
21	Innovative Research of West Florida, Inc.	Clearwater	Florida	United States	33756
22	Avail Clinical Research, LLC	DeLand	Florida	United States	32720
23	Florida Health Center	Fort Lauderdale	Florida	United States	33312
24	Clinical Physiology Associates	Fort Myers	Florida	United States	33916
25	AGA Clinical Trials	Hialeah	Florida	United States	33012
26	Clinical Neuroscience Solutions, Inc.	Jacksonville	Florida	United States	32216
27	Health Awareness, Inc.	Jupiter	Florida	United States	33458
28	Fidelity Clinical Research, Inc.	Lauderhill	Florida	United States	33319
29	Neuroscience Consultants LLC	Miami	Florida	United States	33176
30	International Research Associates, LLC	Miami	Florida	United States	33183
31	Journey Research, Inc	Oldsmar	Florida	United States	34677
32	Clinical Neuroscience Solutions, Inc.	Orlando	Florida	United States	32806
33	Compass Research, LLC	Orlando	Florida	United States	32806
34	Peninsula Research Inc.	Ormond Beach	Florida	United States	32174
35	Advent Clinical Research Centers, Inc.	Pinellas Park	Florida	United States	33781
36	Gold Coast Research, LLC	Plantation	Florida	United States	33317
37	Sarasota Research, LLC	Sarasota	Florida	United States	34243
38	Clinical Research of West Florida, Inc.	Tampa	Florida	United States	33603
39	Southeast Regional Research Group	Columbus	Georgia	United States	31904
40	Georgia Institute for Clinical Research, LLC	Marietta	Georgia	United States	30060
41	Taylor Research, LLC	Marietta	Georgia	United States	30060
42	Better Health Clinical Research, Inc.	Newnan	Georgia	United States	30265
43	Atlanta Knee and Shoulder Clinic, PC	Stockbridge	Georgia	United States	30281
44	Illinois Center for Clinical Research	Chicago	Illinois	United States	60622
45	Rehabilitation Associates of Indiana	Indianapolis	Indiana	United States	46250
46	Northwest Indiana Center for Clinical Research	Valparaiso	Indiana	United States	46383
47	Integrated Clinical Trial Services, Inc.	West Des Moines	Iowa	United States	50265
48	ICRI	Overland Park	Kansas	United States	66210
49	Community Research	Crestview Hills	Kentucky	United States	41017
50	Commonwealth Biomedical Research, LLC	Madisonville	Kentucky	United States	42431
51	Louisiana Research Associates, Inc.	New Orleans	Louisiana	United States	70114
52	IRC Clinics, Inc.	Towson	Maryland	United States	21204
53	Beacon Clinical Research, LLC	Brockton	Massachusetts	United States	02301
54	MedVadis Research Corporation	Watertown	Massachusetts	United States	02472-3930
55	QUEST Research Institute	Bingham Farms	Michigan	United States	48025
56	Medical Research Associates, Inc.	Traverse City	Michigan	United States	49684
57	Healthcare Research Network	Hazelwood	Missouri	United States	63042
58	Medex Healthcare Research, Inc.	Saint Louis	Missouri	United States	63117
59	Advance Clinical Research	Saint Louis	Missouri	United States	63128
60	Mercy Health Research	Saint Louis	Missouri	United States	63141
61	Sundance Clinical Research, LLC	Saint Louis	Missouri	United States	63141
62	Quality Clinical Research	Omaha	Nebraska	United States	68114
63	Advanced Biomedical Research of America	Las Vegas	Nevada	United States	89123
64	Research Facility	Las Vegas	Nevada	United States	89144
65	Comprehensive Clinical Research	Berlin	New Jersey	United States	08009
66	CRI Worldwide LLC	Willingboro	New Jersey	United States	08046
67	Albuquerque Clinical Trials, Inc.	Albuquerque	New Mexico	United States	87102
68	Lovelace Scientific Resources	Albuquerque	New Mexico	United States	87108
69	Drug Trials America	Hartsdale	New York	United States	10530
70	The Medical Research Network, LLC	New York	New York	United States	10128
71	Finger Lakes Clinical Research	Rochester	New York	United States	14618
72	Upstate Clinical Research Associates	Williamsville	New York	United States	14221
73	PMG Research of Charlotte, LLC	Charlotte	North Carolina	United States	28209
74	PMG Research of Wilmington LLC	Wilmington	North Carolina	United States	28401
75	Clinical Trials of America, Inc.	Winston-Salem	North Carolina	United States	27103
76	The Center for Clinical Research	Winston-Salem	North Carolina	United States	27103
77	Daystar Clinical Research, Inc.	Akron	Ohio	United States	44313
78	IVA Research	Cincinnati	Ohio	United States	45245
79	Community Research	Cincinnati	Ohio	United States	45255
80	Bone Joint and Spine Surgeons, Inc.	Toledo	Ohio	United States	43623
81	Cutting Edge Research Group	Oklahoma City	Oklahoma	United States	73116
82	Allegheny Pain Management, P.C.	Altoona	Pennsylvania	United States	16602
83	CRI Worldwide, LLC	Philadelphia	Pennsylvania	United States	19139
84	Founders Research Corporation	Philadelphia	Pennsylvania	United States	19152
85	Tipton Medical & Diagnostic Center	Tipton	Pennsylvania	United States	16684
86	Hartwell Research Group	Anderson	South Carolina	United States	29621
87	Radiant Research, Inc.	Greer	South Carolina	United States	29651
88	Health Concepts	Rapid City	South Dakota	United States	57702
89	Comprehensive Pain Specialists, LLC	Hendersonville	Tennessee	United States	37075
90	Clinical Neuroscience Solutions, Inc.	Memphis	Tennessee	United States	38119
91	Heartland Medical, PC	New Tazewell	Tennessee	United States	37825
92	HCCA Clinical Research Solutions	Smyrna	Tennessee	United States	37167
93	FutureSearch Trials of Neurology	Austin	Texas	United States	78731
94	KRK Medical Research	Dallas	Texas	United States	75230
95	Heights Doctor's Clinic	Houston	Texas	United States	77008
96	R/D Clinical Research, Inc.	Lake Jackson	Texas	United States	77566
97	Sun Research Institute	San Antonio	Texas	United States	78215
98	Aspen Clinical Research	Orem	Utah	United States	84058
99	Advanced Clinical Research	West Jordan	Utah	United States	84088
100	HypotheTest, LLC	Roanoke	Virginia	United States	24018
101	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
102	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: NCT01452529
• Other Study ID Numbers: HYD3002
• First Posted: Oct 17, 2011
• Last Update Posted: Mar 10, 2020
• Last Verified: Mar 1, 2020

• Keywords provided by Purdue Pharma LP: Pain; Opioid
• Additional relevant MeSH terms: Back Pain; Low Back Pain; Hydrocodone

Study Results

Participant Flow

Recruitment Details	First subject first visit: 23-March-2012; Last subject last visit: 03-September-2013. The study was conducted at medical/research sites in the United States.
Pre-assignment Detail	Subjects with moderate to severe chronic low back pain uncontrolled by their current stable analgesic regimen were included.

Arm/Group Title	Open-label Run-in Dose-titration Period Hydrocodone Bitartrate	Hydrocodone Bitartrate	Placebo
Arm/Group Description	The open-label run-in dose-titration period was designed to assess subjects qualification for randomization	Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily	Placebo to match hydrocodone bitartrate once daily tablets Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
Period Title: Run-in Period
STARTED	905	0	0
COMPLETED	592	0	0
NOT COMPLETED	313	0	0
Period Title: Run-in Period
STARTED	0	296	292
COMPLETED	0	229	210
NOT COMPLETED	0	67	82

Baseline Characteristics

Arm/Group Title	Hydrocodone Bitartrate	Placebo	Total
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	Placebo to match hydrocodone bitartrate once daily tablets Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily	Total of all reporting groups
Overall Participants	296	292	588
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.2 (13.51)	47.9 (13.23)	48.6 (13.38)
Sex: Female, Male (Count of Participants)
Female	172 58.1%	166 56.8%	338 57.5%
Male	124 41.9%	126 43.2%	250 42.5%
Race/Ethnicity, Customized (participants) [Number]
White	195 65.9%	207 70.9%	402 68.4%
Black or African American	67 22.6%	51 17.5%	118 20.1%
Asian	25 8.4%	29 9.9%	54 9.2%
American Indian or Alaska Native	2 0.7%	1 0.3%	3 0.5%
Other	7 2.4%	4 1.4%	11 1.9%
Screening Baseline Pain Over the Last 24 Hours (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	7.4 (1.13)	7.4 (1.19)	7.4 (1.16)

Outcome Measures

1. Primary Outcome

Title	Mean Pain Intensity for "Average Pain Over the Last 24 Hours" Score
Description	Mean pain intensity for "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	Week 12

Outcome Measure Data

Analysis Population Description

The full analysis population (N = 588) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug

Arm/Group Title	Hydrocodone Bitartrate	Placebo
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	Placebo to match hydrocodone bitartrate once daily tablets Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
Measure Participants	296	292
Mean (Standard Error) [units on a scale]	3.7 (0.13)	4.2 (0.13)

2. Secondary Outcome

Title	Medical Outcome Study Sleep Scale - Revised (MOS Sleep-R) - Sleep Disturbance Subscale
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 and 6 subscales - sleep disturbance, sleep adequacy, daytime somnolence, snoring, awaken short of breath or with headache, and quantity of sleep. The sleep disturbance subscale comprised the responses to questions 1, 3, 7, and 8 on the assessment. The individual responses for each question were recorded on a 5-point scale with options ranging from 1 - "all of the time" to 5 - "none of the time". Sleep disturbance scores were transformed linearly on a scale of 0-100. A higher value indicates a better score; therefore, a higher score indicates a better sleep pattern.
Time Frame	Weeks 4, 8, and 12

Outcome Measure Data

Analysis Population Description

The full analysis population (N = 588) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug

Arm/Group Title	Hydrocodone Bitartrate	Placebo
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	Placebo to match hydrocodone bitartrate once daily tablets Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
Measure Participants	296	292
Screening	44.38 (9.262)	44.72 (9.871)
Week 4	50.38 (8.851)	50.51 (9.156)
Week 8	50.16 (8.879)	51.16 (8.781)
Week 12	51.57 (8.576)	52.12 (8.779)

3. Secondary Outcome

Title	Patient Global Impression of Change (PGIC)
Description	The PGIC is an ordinal scale which assesses the change in overall status relative to the start of the study. The scale has only 1 item, which measures global change of overall status by the subject on a 7-point scale (very much improved, much improved, minimally improved, no change, minimally worse, much worse, very much worse), where 1 = very much improved and 7 = very much worse. The proportion of subjects responding "very much improved" and "much improved" was summarized by treatment group.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The full analysis population (N = 588) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug

Arm/Group Title	Hydrocodone Bitartrate	Placebo
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	Placebo to match hydrocodone bitartrate once daily tablets Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
Measure Participants	296	292
Total Subjects Completing PGIC	283 95.6%	267 91.4%
Subjects Responding Very Much or Much Improved	173 58.4%	130 44.5%

4. Secondary Outcome

Title	Responder Analysis for Subjects With a ≥ 30% Reduction in Pain Compared to Baseline
Description	A subject's response to treatment was defined as the percentage reduction from the screening mean pain score to the mean pain intensity at week 12 of the double-blind period.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

The full analysis population (N = 588) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug

Arm/Group Title	Hydrocodone Bitartrate	Placebo
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	Placebo to match hydrocodone bitartrate once daily tablets Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
Measure Participants	296	292
Number of Subjects Responding	285 96.3%	280 95.9%
Number of Subjects with ≥ 30% Reduction in Pain	184 62.2%	147 50.3%

5. Secondary Outcome

Title	Responder Analysis for Subjects With a ≥ 50% Reduction in Pain Compared to Baseline
Description	A subject's response to treatment was defined as the percentage reduction from the screening mean pain score to the mean pain intensity at week 12 of the double-blind period.
Time Frame	Baseline to Week 12

Outcome Measure Data

Analysis Population Description

The full analysis population (N = 588) was the group of subjects who were randomized and received at least 1 dose of double-blind study drug

Arm/Group Title	Hydrocodone Bitartrate	Placebo
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	Placebo to match hydrocodone bitartrate once daily tablets Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
Measure Participants	296	292
Number of Subjects Responding	285 96.3%	280 95.9%
Number of Subjects with ≥ 50% Reduction in Pain	137 46.3%	109 37.3%

Adverse Events

Time Frame	Adverse events (AEs) were reported from start of study participation through the period beyond study completion.
Adverse Event Reporting Description	AEs were learned of through spontaneous reports and/or subject interview, or were 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 following the last study visit were followed until the AE or sequelae resolved or stabilized.
Arm/Group Title	Open-label Run-in Dose-titration Period Hydrocodone Bitartrate		Hydrocodone Bitartrate		Placebo
Arm/Group Description	The open-label run-in dose-titration period was designed to assess subjects' qualification for randomization		Hydrocodone bitartrate (HYD) once daily (q24h) tablets Hydrocodone bitartrate q24h film-coated tablets: Hydrocodone bitartrate q24h film-coated tablets 20 - 120 mg once daily		Placebo to match hydrocodone bitartrate once daily tablets Placebo to match hydrocodone bitartrate q24h tablets: Placebo to match hydrocodone bitartrate q24h film coated tablets 20 - 120 mg once daily
All Cause Mortality
	Open-label Run-in Dose-titration Period Hydrocodone Bitartrate		Hydrocodone Bitartrate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Open-label Run-in Dose-titration Period Hydrocodone Bitartrate		Hydrocodone Bitartrate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/905 (0.8%)		2/296 (0.7%)		4/292 (1.4%)
Cardiac disorders
Angina unstable	1/905 (0.1%)		0/296 (0%)		0/292 (0%)
Atrial fibrillation	0/905 (0%)		0/296 (0%)		1/292 (0.3%)
Endocrine disorders
Hypothyroidism	0/905 (0%)		1/296 (0.3%)		0/292 (0%)
Gastrointestinal disorders
Abdominal pain	1/905 (0.1%)		0/296 (0%)		0/292 (0%)
Vomiting	1/905 (0.1%)		0/296 (0%)		0/292 (0%)
General disorders
Chest pain	0/905 (0%)		1/296 (0.3%)		0/292 (0%)
Hepatobiliary disorders
Cholecystitis	0/905 (0%)		0/296 (0%)		1/292 (0.3%)
Infections and infestations
Lobar pneumonia	0/905 (0%)		0/296 (0%)		1/292 (0.3%)
Injury, poisoning and procedural complications
Concussion	0/905 (0%)		0/296 (0%)		1/292 (0.3%)
Post procedural haemorrhage	1/905 (0.1%)		0/296 (0%)		0/292 (0%)
Musculoskeletal and connective tissue disorders
Arthritis	1/905 (0.1%)		0/296 (0%)		0/292 (0%)
Joint effusion	1/905 (0.1%)		0/296 (0%)		0/292 (0%)
Musculoskeletal chest pain	0/905 (0%)		0/296 (0%)		1/292 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of lung	0/905 (0%)		0/296 (0%)		1/292 (0.3%)
Nervous system disorders
Intracranial aneurysm	1/905 (0.1%)		0/296 (0%)		0/292 (0%)
Psychiatric disorders
Drug abuse	1/905 (0.1%)		0/296 (0%)		0/292 (0%)
Major depression	0/905 (0%)		1/296 (0.3%)		0/292 (0%)
Reproductive system and breast disorders
Ovarian cyst ruptured	1/905 (0.1%)		0/296 (0%)		0/292 (0%)
Respiratory, thoracic and mediastinal disorders
Emphysema	0/905 (0%)		0/296 (0%)		1/292 (0.3%)
Respiratory failure	0/905 (0%)		0/296 (0%)		1/292 (0.3%)
Surgical and medical procedures
Abortion induced	1/905 (0.1%)		0/296 (0%)		0/292 (0%)
Other (Not Including Serious) Adverse Events
	Open-label Run-in Dose-titration Period Hydrocodone Bitartrate		Hydrocodone Bitartrate		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	265/905 (29.3%)		52/296 (17.6%)		30/292 (10.3%)
Gastrointestinal disorders
Nausea	144/905 (15.9%)		24/296 (8.1%)		16/292 (5.5%)
Constipation	85/905 (9.4%)		10/296 (3.4%)		7/292 (2.4%)
Vomiting	65/905 (7.2%)		18/296 (6.1%)		9/292 (3.1%)
Nervous system disorders
Dizziness	64/905 (7.1%)		9/296 (3%)		5/292 (1.7%)
Headache	59/905 (6.5%)		6/296 (2%)		5/292 (1.7%)

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.