Long-Term Study of Hydrocodone Bitartrate Controlled-release Capsules in Subjects With Chronic Pain

• Sponsor: Zogenix, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01115569
• Collaborator: (none)
• Enrollment: 424
• Locations: 50
• Arm: 1
• Duration (Months): 20
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This Phase 3, multi-center study will evaluate the long-term safety and tolerability of hydrocodone bitartrate controlled release capsule (HC-CR) at daily doses of 40 mg or more in subjects with moderate to severe chronic pain. Long-term maintenance of HC-CR efficacy will be evaluated.

Condition or Disease	Intervention/Treatment	Phase
Chronic Pain	Drug: Hydrocodone Bitartrate	Phase 3

Detailed Description

Subjects will go through screening, an open-label conversion and titration phase of up to 6 weeks followed by an open-label treatment phase for up to 48 weeks with a 2 week follow-up period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 424 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Long-Term Open-Label Safety Study of Hydrocodone Bitartrate Controlled-Release Capsules With Flexible Dosing to Treat Subjects With Moderate to Severe Chronic Pain
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hydrocodone Bitartrate Open-label, all patients fulfilling the protocol Inclusion/Exclusion criteria will receive HC-CR in a flexible dosing regimen.	Drug: Hydrocodone Bitartrate; Open-Label, Capsule Strengths 10 mg, 20 mg, 30 mg, 40 mg, 50 mg; by mouth (PO) twice a day (BID) for up to 48 weeks; Other Names: Hydrocodone Bitartrate Controlled Release (HC-CR)

Outcome Measures

Primary Outcome Measures

1. Mean Change in Average Daily Pain [1 year]

   Numeric Rating Scale (NRS) for Pain (0-10; where 0 = no pain, 10 = worst pain imaginable) recorded up to 54 weeks, starting at screening through end of study. Lower number equals better outcome.

Secondary Outcome Measures

1. Maintenance of Efficacy [1 year]

   Clinic Numeric Rating Scale (NRS), Brief Pain Inventory (BPI), Oswestry Disability Index, Hospital Anxiety and Depression Scale, Rescue Doses and Subject Global of Medication

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must have a diagnosed moderate to severe chronic pain condition treated with around-the-clock opioids for at least the past 3 months or in the Investigator's opinion qualify for around-the-clock opioid therapy for treatment of their pain

• Subjects must have been taking opioids at least 5 days/week for the past month at an average daily dose of at least 30 mg hydrocodone

• Subjects must be able to complete study procedures and attend clinic visits for 6 to 12 months

• Females subjects of childbearing potential must have a negative urine pregnancy test at the Screen Visit, and must consent to use a medically-acceptable method of contraception throughout the entire study period.

• Subjects must have had an adequate medical evaluation for the treatment of their underlying painful condition and appropriate primary medical/surgical therapies for the underlying condition

• Subjects must voluntarily provide written informed consent

Exclusion Criteria:

• Any clinically significant condition that would, in the opinion of the investigator, preclude study participation or interfere with the assessment of pain or increase the risk of opioid-related adverse events (AEs)

• A medical condition that, in the opinion of the Investigator, would compromise the subject's ability to swallow, absorb, metabolize, or excrete study drug

• A surgical procedure for pain within the last 3 months

• Uncontrolled blood pressure, i.e., a sitting systolic blood pressure >180 mm Hg or <90 mm Hg, and/or a sitting diastolic blood pressure >120 mm Hg or <50 mm Hg at Screening

• A body mass index (BMI) > 45 kg/m2

• A hospital anxiety and depression scale (HADS) score of >12 in either depression or anxiety subscales or an established history of any psychiatric disorder that is poorly controlled

• A clinically significant abnormality in clinical chemistry, hematology or urinalysis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Research Center	Phoenix	Arizona	United States	85023
2	HOPE Research Institute, LLC	Phoenix	Arizona	United States	85050
3	Cochise Clinical Research	Sierra Vista	Arizona	United States	85635
4	Ortho Research	Little Rock	Arkansas	United States	72205
5	Pain Institute of California	Bakersfield	California	United States	93311
6	Providence Clinical Research	Burbank	California	United States	91505
7	South Orange County Surgical Medical Group	Laguna Hills	California	United States	92653
8	Scripps Clinic, Clinical Research	San Diego	California	United States	92128
9	Mountain View Clinical Research, Inc.	Golden	Colorado	United States	80401
10	Stamford Therapeutics Consortium	Stamford	Connecticut	United States	06905
11	Florida Institute of Medical Research	Jacksonville	Florida	United States	32257
12	Gold Coast Research, LLC	Plantation	Florida	United States	33317
13	Advanced Research Institute, Inc.	Trinity	Florida	United States	34655
14	National Pain Research Institute, Inc.	Winter Park	Florida	United States	32789
15	Best Clinical Research	Decatur	Georgia	United States	30034
16	Georgia Institute for Clinical Research, LLC	Marietta	Georgia	United States	30060
17	Better Health Clinical Research, Inc	Newnan	Georgia	United States	30265
18	Nautical Clinical Research, LLC	Boise	Idaho	United States	83702
19	Suburban Clinical Research	Bolingbrook	Illinois	United States	60490
20	International Clinical Research Institute, Inc.	Leawood	Kansas	United States	66211
21	Clinical Trials Technology, Inc.	Prairie Village	Kansas	United States	66206
22	Clinical Trials Managements, LLC	Mandeville	Louisiana	United States	70471
23	Willis-Knighton Physician Network	Shreveport	Louisiana	United States	71101
24	New England Center for Clinical Research, Internal Medicine and Cardiology Associates, LLC	Fall River	Massachusetts	United States	02720
25	Infinity Medical Research, Inc.	North Dartmouth	Massachusetts	United States	02747
26	Mid-South Anesthesia Consultants	Southaven	Mississippi	United States	38671
27	Mercy Health Research	Saint Louis	Missouri	United States	63141
28	Clinvest	Springfield	Missouri	United States	65807
29	Research West, LLC	Kalispell	Montana	United States	59901
30	Lovelace Scientific Resources, Inc.	Albuquerque	New Mexico	United States	87108
31	Long Island Gastrointestinal Research Group	Great Neck	New York	United States	11023
32	New York University Pain Management Center	New York	New York	United States	10016
33	The Center for Clinical Research, LLC	Winston Salem	North Carolina	United States	27103
34	Valley Medical Group, PC	Centerville	Ohio	United States	45459
35	Prestige Clinical Research	Franklin	Ohio	United States	45005
36	Hometown Urgent Care and Research	Springfield	Ohio	United States	45504
37	Hillcrest Clinical Research, Inc.	Oklahoma City	Oklahoma	United States	73119
38	Memorial Clinical Research DBA Angelique Barreto, MD	Oklahoma City	Oklahoma	United States	73134
39	Blair Medical Associates	Altoona	Pennsylvania	United States	16602
40	CRI Worldwide, LLC	Philadelphia	Pennsylvania	United States	19139
41	New England Center for Clinical Research, Inc.	Cranston	Rhode Island	United States	02920
42	Renaissance Clinical Research and Hypertension Clinic	Dallas	Texas	United States	75235
43	The Clinical Research Center, LLC	Fort Worth	Texas	United States	76104
44	Heights Doctors Clinic	Houston	Texas	United States	77008
45	Clinical Trial Network	Houston	Texas	United States	77074
46	Quality Research, Inc.	San Antonio	Texas	United States	78209
47	West Side Medical	Clinton	Utah	United States	84015
48	Jean Brown Research	Salt Lake City	Utah	United States	84124
49	Advanced Pain Management	Virginia Beach	Virginia	United States	23454
50	Northwest Clinical Research Center	Bellevue	Washington	United States	98007

Sponsors and Collaborators

• Zogenix, Inc.

Investigators

• Study Director: Vickie Gorgone, Zogenix, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Zogenix, Inc.
• ClinicalTrials.gov Identifier: NCT01115569
• Other Study ID Numbers: ZX002-0802
• First Posted: May 4, 2010
• Last Update Posted: Apr 25, 2014
• Last Verified: Mar 1, 2014

• Keywords provided by Zogenix, Inc.: chronic pain
• Additional relevant MeSH terms: Chronic Pain; Hydrocodone

Study Results

Participant Flow

Pre-assignment Detail	Out of 638 subjects treated with Hydrocodone Bitartate Extended Release (HC-ER) capsules in the Conversion/Titration Phase, 214 subjects discontinued early and 424 continued in the Maintenance HC-ER Treatment Phase; 285 subjects completed.

Arm/Group Title	Open-label Hydrocodone Bitartrate Extended Release (HC-ER)	Open-label Hydrocodone Bitartrate Extended Release Capsules
Arm/Group Description	Conversion/Titration Phase: HC-ER capsules daily for up to 6 weeks	Maintenance HC-ER Treatment Phase: Open-label, all patients fulfilling the protocol Inclusion/Exclusion criteria will receive HC-ER in a flexible dosing regimen. Hydrocodone Bitartrate: Open-Label, Capsule Strengths 10 mg, 20 mg, 30 mg, 40 mg, 50 mg; by mouth (PO) twice a day (BID) for up to 48 weeks
Period Title: Conversion/Titration Phase
STARTED	638	0
COMPLETED	424	0
NOT COMPLETED	214	0
Period Title: Conversion/Titration Phase
STARTED	0	424
COMPLETED	0	285
NOT COMPLETED	0	139

Baseline Characteristics

Arm/Group Title	Open-label Hydrocodone Bitartate Extended Release (HC-ER)
Arm/Group Description	Conversion/Titration Phase: HC-ER capsules daily for up to 6 weeks
Overall Participants	638
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	572 89.7%
>=65 years	66 10.3%
Sex: Female, Male (Count of Participants)
Female	360 56.4%
Male	278 43.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 0.5%
Asian	1 0.2%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	107 16.8%
White	518 81.2%
More than one race	9 1.4%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	638 100%

Outcome Measures

1. Primary Outcome

Title	Mean Change in Average Daily Pain
Description	Numeric Rating Scale (NRS) for Pain (0-10; where 0 = no pain, 10 = worst pain imaginable) recorded up to 54 weeks, starting at screening through end of study. Lower number equals better outcome.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The number of participants for analysis was determined by the safety population. Numeric Rating Scale (NRS) for Pain assessment was used. Measure is mean change in average daily pain intensity. Total number of participants providing end of study pain intensity score = 391.

Arm/Group Title	Open-label Hydrocodone Bitartrate Extended Release Capsules
Arm/Group Description	Maintenance HC-ER Treatment Phase: Open-label, all patients fulfilling the protocol Inclusion/Exclusion criteria will receive HC-CR in a flexible dosing regimen. Hydrocodone Bitartrate: Open-Label, Capsule Strengths 10 mg, 20 mg, 30 mg, 40 mg, 50 mg; by mouth (PO) twice a day (BID) for up to 48 weeks
Measure Participants	391
Mean (Standard Deviation) [units on a scale]	0.921 (2.2)

2. Secondary Outcome

Title	Maintenance of Efficacy
Description	Clinic Numeric Rating Scale (NRS), Brief Pain Inventory (BPI), Oswestry Disability Index, Hospital Anxiety and Depression Scale, Rescue Doses and Subject Global of Medication
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Adverse events (AEs) were recorded up to 54 weeks, beginning at the Conversion and Titration Phase through 2 weeks after the last treatment administration (Treatment Phase).
Adverse Event Reporting Description	Subjects received a follow up phone call 14 days after the end of study to collect information regarding adverse events (AEs) or new serious AEs that occurred during this time period.
Arm/Group Title	Conversion/Titration Phase		Maintenance Treatment Phase
Arm/Group Description	Conversion/Titration Phase: Hydrocodone Bitartrate Extended Release (HC-ER) capsules daily for up to 6 weeks		Maintenance Hydrocodone Bitartrate Extended Release (HC-ER) Treatment Phase: Open-label, all patients fulfilling the protocol Inclusion/Exclusion criteria will receive HC-CR in a flexible dosing regimen. Hydrocodone Bitartrate: Open-Label, Capsule Strengths 10 mg, 20 mg, 30 mg, 40 mg, 50 mg; by mouth (PO) twice a day (BID) for up to 48 weeks
All Cause Mortality
	Conversion/Titration Phase		Maintenance Treatment Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Conversion/Titration Phase		Maintenance Treatment Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	26/638 (4.1%)		73/424 (17.2%)
Blood and lymphatic system disorders
Anaemia	0/638 (0%)		1/424 (0.2%)
Cardiac disorders
Atrial fibrillation	1/638 (0.2%)		1/424 (0.2%)
Cardiac failure congestive	1/638 (0.2%)		0/424 (0%)
Coronary artery disease	1/638 (0.2%)		0/424 (0%)
Myocardial infarction	1/638 (0.2%)		0/424 (0%)
Arteriosclerosis coronary artery	0/638 (0%)		1/424 (0.2%)
Gastrointestinal disorders
Gastric ulcer	1/638 (0.2%)		0/424 (0%)
Retroperitoneal haemorrage	1/638 (0.2%)		0/424 (0%)
Small intestinal obstruction	0/638 (0%)		2/424 (0.5%)
Constipation	0/638 (0%)		1/424 (0.2%)
Erosive oesophagitis	0/638 (0%)		1/424 (0.2%)
Gastritis	0/638 (0%)		1/424 (0.2%)
Ileitis	0/638 (0%)		1/424 (0.2%)
Pancreatitis	0/638 (0%)		1/424 (0.2%)
General disorders
Non-cardiac chest pain	2/638 (0.3%)		1/424 (0.2%)
Chest pain	1/638 (0.2%)		1/424 (0.2%)
Infections and infestations
Cystitis	1/638 (0.2%)		0/424 (0%)
Enterococcal infection	1/638 (0.2%)		0/424 (0%)
Gastroenteritis	1/638 (0.2%)		1/424 (0.2%)
Pneumonia	1/638 (0.2%)		3/424 (0.7%)
Sepsis	1/638 (0.2%)		1/424 (0.2%)
Urinary tract infection	1/638 (0.2%)		1/424 (0.2%)
Viral infection	1/638 (0.2%)		1/424 (0.2%)
Abscess limb	0/638 (0%)		1/424 (0.2%)
Cellulitis	0/638 (0%)		1/424 (0.2%)
Diverticulitis	0/638 (0%)		1/424 (0.2%)
Extradural abscess	0/638 (0%)		1/424 (0.2%)
Gastroenteritis viral	0/638 (0%)		1/424 (0.2%)
Influenza	0/638 (0%)		1/424 (0.2%)
Mastitis	0/638 (0%)		1/424 (0.2%)
Oesophageal candidiasis	0/638 (0%)		1/424 (0.2%)
Pathogen resistance	0/638 (0%)		1/424 (0.2%)
Pneumonia staphylococcal	0/638 (0%)		1/424 (0.2%)
Pyelonephritis	0/638 (0%)		1/424 (0.2%)
Staphylococcal bacteraemia	0/638 (0%)		1/424 (0.2%)
Staphylococcal sepsis	0/638 (0%)		1/424 (0.2%)
Injury, poisoning and procedural complications
Intenstional overdose	0/638 (0%)		2/424 (0.5%)
Ankle fracture	0/638 (0%)		1/424 (0.2%)
Drug toxicity	0/638 (0%)		1/424 (0.2%)
Gun shot wound	0/638 (0%)		1/424 (0.2%)
Incisional hernia	0/638 (0%)		1/424 (0.2%)
Procedural pain	0/638 (0%)		1/424 (0.2%)
Skull fracture	0/638 (0%)		1/424 (0.2%)
Investigations
Blood potassium decreased	1/638 (0.2%)		0/424 (0%)
Lipase increased	0/638 (0%)		1/424 (0.2%)
Metabolism and nutrition disorders
Dehydration	0/638 (0%)		2/424 (0.5%)
Hypokalaemia	0/638 (0%)		1/424 (0.2%)
Musculoskeletal and connective tissue disorders
Osteoarthrtis	1/638 (0.2%)		4/424 (0.9%)
Pain in extremity	1/638 (0.2%)		0/424 (0%)
Back pain	0/638 (0%)		1/424 (0.2%)
Intervertebral disc degeneration	0/638 (0%)		1/424 (0.2%)
Joint instability	0/638 (0%)		1/424 (0.2%)
Musculoskeletal chest pain	0/638 (0%)		1/424 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/638 (0%)		1/424 (0.2%)
Non-small cell lung cancer stage IV	0/638 (0%)		1/424 (0.2%)
Nervous system disorders
Lethargy	1/638 (0.2%)		0/424 (0%)
Mental impairment	1/638 (0.2%)		1/424 (0.2%)
Dizziness	0/638 (0%)		1/424 (0.2%)
Myasthenia gravis	0/638 (0%)		1/424 (0.2%)
Syncope	0/638 (0%)		1/424 (0.2%)
Transient ischemic attack	0/638 (0%)		1/424 (0.2%)
Tremor	0/638 (0%)		1/424 (0.2%)
Psychiatric disorders
Completed suicide	0/638 (0%)		1/424 (0.2%)
Depression	0/638 (0%)		1/424 (0.2%)
Suicidal ideation	0/638 (0%)		1/424 (0.2%)
Suicidal attempt	0/638 (0%)		1/424 (0.2%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/638 (0.2%)		0/424 (0%)
Chronic obstructive pulmonary disease	1/638 (0.2%)		5/424 (1.2%)
Pulmonary embolism	1/638 (0.2%)		1/424 (0.2%)
Asthma	0/638 (0%)		1/424 (0.2%)
Respiratory failure	0/638 (0%)		1/424 (0.2%)
Vascular disorders
Hypertension	1/638 (0.2%)		0/424 (0%)
Venous insufficiency	1/638 (0.2%)		0/424 (0%)
Deep vein thrombosis	0/638 (0%)		1/424 (0.2%)
Other (Not Including Serious) Adverse Events
	Conversion/Titration Phase		Maintenance Treatment Phase
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	277/638 (43.4%)		298/424 (70.3%)
Gastrointestinal disorders
Constipation	72/638 (11.3%)		53/424 (12.5%)
Nausea	68/638 (10.7%)		42/424 (9.9%)
Vomiting	26/638 (4.1%)		41/424 (9.7%)
Diarrhoea	20/638 (3.1%)		17/424 (4%)
Toothache	2/638 (0.3%)		9/424 (2.1%)
General disorders
Fatigue	23/638 (3.6%)		15/424 (3.5%)
Oedema peripheral	14/638 (2.2%)		14/424 (3.3%)
Pyrexia	11/638 (1.7%)		15/424 (3.5%)
Infections and infestations
Urinary tract infection	6/638 (0.9%)		28/424 (6.6%)
Upper respiratory tract infection	7/638 (1.1%)		25/424 (5.9%)
Nasopharyngitis	11/638 (1.7%)		24/424 (5.7%)
Sinusitis	9/638 (1.4%)		23/424 (5.4%)
Bronchitis	10/638 (1.6%)		20/424 (4.7%)
Influenza	4/638 (0.6%)		20/424 (4.7%)
Gastroenteritis viral	6/638 (0.9%)		10/424 (2.4%)
Pneumonia	3/638 (0.5%)		9/424 (2.1%)
Injury, poisoning and procedural complications
Fall	8/638 (1.3%)		25/424 (5.9%)
Contusion	4/638 (0.6%)		14/424 (3.3%)
Muscle strain	9/638 (1.4%)		13/424 (3.1%)
Musculoskeletal and connective tissue disorders
Back Pain	9/638 (1.4%)		47/424 (11.1%)
Arthralgia	9/638 (1.4%)		33/424 (7.8%)
Neck pain	3/638 (0.5%)		19/424 (4.5%)
Musculoskeletal pain	4/638 (0.6%)		18/424 (4.2%)
Muscle spasms	11/638 (1.7%)		16/424 (3.8%)
Pain in extremity	7/638 (1.1%)		14/424 (3.3%)
Osteoarthritis	2/638 (0.3%)		11/424 (2.6%)
Nervous system disorders
Somnolence	49/638 (7.7%)		18/424 (4.2%)
Headache	48/638 (7.5%)		29/424 (6.8%)
Dizziness	18/638 (2.8%)		13/424 (3.1%)
Migraine	5/638 (0.8%)		11/424 (2.6%)
Paraesthesia	1/638 (0.2%)		9/424 (2.1%)
Psychiatric disorders
Anxiety	8/638 (1.3%)		23/424 (5.4%)
Insomnia	24/638 (3.8%)		21/424 (5%)
Depression	6/638 (0.9%)		16/424 (3.8%)
Respiratory, thoracic and mediastinal disorders
Cough	6/638 (0.9%)		9/424 (2.1%)
Skin and subcutaneous tissue disorders
Pruritus allergic	13/638 (2%)		0/424 (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.