Clinical trial NCT01400139: 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.
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Nonmalignant and Nonneuropathic Pain
Keywords: Pain
Nonmalignant pain
Nonneuropathic Pain
Opioid
Lead sponsor: Purdue Pharma LP
Sponsor class: INDUSTRY
First posted: 2011-07-22
Enrollment: 922
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: The Number of Participants With Adverse Events as a Measure of Safety
timeFrame: Up to 84 weeks
measure: Daily "Average Pain Over the Last 24 Hours"
timeFrame: 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)
Secondary outcomes:
measure: "Pain Right Now" Score
timeFrame: Week 12
measure: Medical Outcomes Study (MOS) Sleep Scale - Revised (MOS Sleep-R)
timeFrame: Baseline and up to 52 weeks in the Core Study maintenance period, and up to 24 weeks in the Extension Period
measure: Brief Pain Inventory Short Form (BPI-SF)
timeFrame: Up to 52 weeks in the Core Study maintenance period, and up to 24 weeks in the Extension Period
measure: Medical Outcomes Study 36-item Short Form (SF-36)
timeFrame: Up to 52 weeks in the Core Study maintenance period, and up to 24 weeks in the Extension Period
measure: Patient Global Impression of Change (PGIC)
timeFrame: At Week 52 in the Core Study maintenance period and at Week 24 in the Extension Period
measure: Treatment Satisfaction Questionnaire (TSQ) - Part I
timeFrame: At Week 52 or upon early discontinuation at or before Week 4 in the Core Study maintenance period
measure: Treatment Satisfaction Questionnaire (TSQ) - Part II
timeFrame: At Week 52 or upon early discontinuation at or before Week 4 in maintenance and at Week 24 in extension
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alliance Clinical Research
state: Alabama
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: Tucson
country: United States
facility: Genova Clinical Research
state: Arizona
city: Tucson
country: United States
facility: Quality of Life Medical & Research Center, LLC
state: Arizona
city: Anaheim
country: United States
facility: ACRI -Phase1, LLC
state: California
city: Anaheim
country: United States
facility: United Clinical Research Center, Inc.
state: California
city: Carmichael
country: United States
facility: Med Center
state: California
city: Fresno
country: United States
facility: Research Center of Fresno, Inc.
state: California
city: La Mesa
country: United States
facility: TriWest Research Associates
state: California
city: Lomita
country: United States
facility: Torrance Clinical Research
state: California
city: Long Beach
country: United States
facility: Skyline Research, LLC
state: California
city: Pasadena
country: United States
facility: Lotus Clinical Research, LLC
state: California
city: Richmond
country: United States
facility: Center for Clinical Research, Inc
state: California
city: Sacramento
country: United States
facility: Northern California Research
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research
state: California
city: Waterbury
country: United States
facility: Chase Medical Research, LLC
state: Connecticut
city: Bradenton
country: United States
facility: Meridien Research
state: Florida
city: Clearwater
country: United States
facility: Innovative Research of West Florida, Inc.
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Fort Myers
country: United States
facility: Clinical Physiology Associates
state: Florida
city: Hallandale Beach
country: United States
facility: MD Clinical
state: Florida
city: Hialeah
country: United States
facility: AGA Clinical Trials
state: Florida
city: Jacksonville
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Florida
city: Jupiter
country: United States
facility: Health Awareness, Inc.
state: Florida
city: Lauderhill
country: United States
facility: Fidelity Clinical Research, Inc.
state: Florida
city: Miami
country: United States
facility: Neuroscience Consultants LLC
state: Florida
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Ormond Beach
country: United States
facility: Peninsula Research, Inc.
state: Florida
city: Plantation
country: United States
facility: Gold Coast Research, LLC
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Columbus
country: United States
facility: Southeast Regional Research Group
state: Georgia
city: Marietta
country: United States
facility: Georgia Institute for Clinical Research, LLC
state: Georgia
city: Marietta
country: United States
facility: Taylor Research, LLC
state: Georgia
city: Stockbridge
country: United States
facility: Atlanta Knee and Shoulder Clinic, PC
state: Georgia
city: Chicago
country: United States
facility: Illinois Center for Clinical Research
state: Illinois
city: Indianapolis
country: United States
facility: Rehabilitation Associates of Indiana
state: Indiana
city: Valparaiso
country: United States
facility: Northwest Indiana Center for Clinical Research
state: Indiana
city: West Des Moines
country: United States
facility: Integrated Clinical Trial Services, Inc.
state: Iowa
city: Leawood
country: United States
facility: ICRI
state: Kansas
city: Crestview Hills
country: United States
facility: Community Research
state: Kentucky
city: Madisonville
country: United States
facility: Commonwealth Biomedical Research, LLC
state: Kentucky
city: New Orleans
country: United States
facility: Louisiana Research Associates, Inc.
state: Louisiana
city: Brockton
country: United States
facility: Beacon Clinical Research, LLC
state: Massachusetts
city: Watertown
country: United States
facility: MedVadis Research Corporation
state: Massachusetts
city: Traverse City
country: United States
facility: Medical Research Associates, Inc.
state: Michigan
city: Saint Louis
country: United States
facility: Medex Healthcare Research, Inc.
state: Missouri
city: Saint Louis
country: United States
facility: Advance Clinical Research
state: Missouri
city: Saint Louis
country: United States
facility: Mercy Health Research
state: Missouri
city: Saint Louis
country: United States
facility: Sundance Clinical Research, LLC
state: Missouri
city: Omaha
country: United States
facility: Quality Clinical Research
state: Nebraska
city: Las Vegas
country: United States
facility: Advanced Biomedical Research of America
state: Nevada
city: Las Vegas
country: United States
facility: Research Facility
state: Nevada
city: Berlin
country: United States
facility: Comprehensive Clinical Research
state: New Jersey
city: Willingboro
country: United States
facility: CRI Worldwide LLC
state: New Jersey
city: Albuquerque
country: United States
facility: Lovelace Scientific Resources
state: New Mexico
city: Hartsdale
country: United States
facility: Drug Trials America
state: New York
city: New York
country: United States
facility: Research Across America
state: New York
city: New York
country: United States
facility: The Medical Research Network, LLC
state: New York
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Williamsville
country: United States
facility: Upstate Clinical Research Associates
state: New York
city: Charlotte
country: United States
facility: PMG Research of Charlotte, LLC
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: Clinical Trials of America, Inc.
state: North Carolina
city: Winston-Salem
country: United States
facility: The Center for Clinical Research
state: North Carolina
city: Akron
country: United States
facility: Daystar Clinical Research, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: IVA Research
state: Ohio
city: Cincinnati
country: United States
facility: Community Research
state: Ohio
city: Toledo
country: United States
facility: Bone Joint and Spine Surgeons, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: Cutting Edge Research Group
state: Oklahoma
city: Altoona
country: United States
facility: Allegheny Pain Management, P.C.
state: Pennsylvania
city: Bensalem
country: United States
facility: Pennsylvania Research Institute
state: Pennsylvania
city: Philadelphia
country: United States
facility: CRI Worldwide LLC
state: Pennsylvania
city: Philadelphia
country: United States
facility: Founders Research Corporation
state: Pennsylvania
city: Tipton
country: United States
facility: Tipton Medical & Diagnostic Center
state: Pennsylvania
city: Anderson
country: United States
facility: Hartwell Research Group
state: South Carolina
city: Charleston
country: United States
facility: Pain Research of Charleston
state: South Carolina
city: Greer
country: United States
facility: Radiant Research, Inc.
state: South Carolina
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Memphis
country: United States
facility: Clinical Neuroscience Solutions, Inc.
state: Tennessee
city: New Tazewell
country: United States
facility: Heartland Medical, PC
state: Tennessee
city: Smyrna
country: United States
facility: HCCA Clinical Research Solutions
state: Tennessee
city: Austin
country: United States
facility: FutureSearch Trials of Neurology
state: Texas
city: Austin
country: United States
facility: Lovelace Scientific Resources, Inc.
state: Texas
city: Dallas
country: United States
facility: KRK Medical Research
state: Texas
city: Houston
country: United States
facility: Heights Doctor's Clinic
state: Texas
city: Houston
country: United States
facility: JVC Family Medicine
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions, Inc.
state: Texas
city: Killeen
country: United States
facility: TEAM Research of Central Texas
state: Texas
city: Lake Jackson
country: United States
facility: R/D Clinical Research, Inc.
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
state: Texas
city: Tomball
country: United States
facility: Martin Diagnostic Clinic
state: Texas
city: Orem
country: United States
facility: Aspen Clinical Research
state: Utah
city: West Jordan
country: United States
facility: Advanced Clinical Research
state: Utah
city: Roanoke
country: United States
facility: HypotheTest, LLC
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
city: Edmonds
country: United States
facility: Washington Center for Pain Management
state: Washington
Study officials:
References:
citation: Wen W, Taber L, Lynch SY, He E, Ripa S. 12-Month safety and effectiveness of once-daily hydrocodone tablets formulated with abuse-deterrent properties in patients with moderate to severe chronic pain. J Opioid Manag. 2015 Jul-Aug;11(4):339-56. doi: 10.5055/jom.2015.0283.
citation: Campbell K, Kutz JW Jr, Shoup A, Wen W, Lynch SY, He E, Ripa SR. Evaluation of the Ototoxicity Potential of Once-Daily, Single-Entity Hydrocodone in Patients with Chronic Pain: Results of Two Phase-3 Clinical Studies. Pain Physician. 2017 Jan-Feb;20(1):E183-E193.
citation: Kapil RP, Cipriano A, Wen W, Yu Lynch S, He E, Colucci SV, Harris SC. Pharmacokinetic Profile and Sustained 24-hour Analgesia of a Once-daily Hydrocodone Bitartrate Extended-release Tablet with Abuse-deterrent Properties. Clin Ther. 2016 Feb;38(2):302-14. doi: 10.1016/j.clinthera.2015.12.003. Epub 2015 Dec 31.
citation: Taber L, Lynch SY, He E, Ripa SR. Long-term safety and effectiveness of once-daily, single-entity, extended-release hydrocodone over 76 weeks of an open-label study in patients with chronic noncancer and nonneuropathic pain. Postgrad Med. 2016 Jan;128(1):23-33. doi: 10.1080/00325481.2016.1134022. Epub 2016 Jan 12.