Clinical trial NCT01452529: Efficacy and Safety of Hydrocodone Bitartrate (HYD) in Subjects With Moderate to Severe Chronic Low Back Pain
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Low Back Pain
Keywords: Pain
Opioid
Lead sponsor: Purdue Pharma LP
Sponsor class: INDUSTRY
First posted: 2011-10-17
Enrollment: 905
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Mean Pain Intensity for "Average Pain Over the Last 24 Hours" Score
timeFrame: Week 12
Secondary outcomes:
measure: Medical Outcome Study Sleep Scale - Revised (MOS Sleep-R) - Sleep Disturbance Subscale
timeFrame: Weeks 4, 8, and 12
measure: Patient Global Impression of Change (PGIC)
timeFrame: Week 12
measure: Responder Analysis for Subjects With a ≥ 30% Reduction in Pain Compared to Baseline
timeFrame: Baseline to Week 12
measure: Responder Analysis for Subjects With a ≥ 50% Reduction in Pain Compared to Baseline
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alliance Clinical Research
state: Alabama
city: Mobile
country: United States
facility: Coastal Clinical Research, Inc.
state: Alabama
city: Phoenix
country: United States
facility: Arizona Research Center
state: Arizona
city: Phoenix
country: United States
facility: Redpoint Research
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: Tucson
country: United States
facility: Redpoint Research
state: Arizona
city: Anaheim
country: United States
facility: ACRI-Phase 1, LLC
state: California
city: Anaheim
country: United States
facility: Orange County Research Institute
state: California
city: Anaheim
country: United States
facility: United Clinical Research Center, Inc.
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 Institute Inc.
state: California
city: Long Beach
country: United States
facility: Skyline 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: Boynton Beach
country: United States
facility: Orthopedic Research Institute
state: Florida
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 Lauderdale
country: United States
facility: Florida Health Center
state: Florida
city: Fort Myers
country: United States
facility: Clinical Physiology Associates
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: Miami
country: United States
facility: International Research Associates, LLC
state: Florida
city: Oldsmar
country: United States
facility: Journey Research, Inc
state: Florida
city: Orlando
country: United States
facility: Clinical Neuroscience Solutions, Inc.
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: Pinellas Park
country: United States
facility: Advent Clinical Research Centers, Inc.
state: Florida
city: Plantation
country: United States
facility: Gold Coast Research, LLC
state: Florida
city: Sarasota
country: United States
facility: Sarasota 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: Newnan
country: United States
facility: Better Health Clinical Research, Inc.
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: Overland Park
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: Towson
country: United States
facility: IRC Clinics, Inc.
state: Maryland
city: Brockton
country: United States
facility: Beacon Clinical Research, LLC
state: Massachusetts
city: Watertown
country: United States
facility: MedVadis Research Corporation
state: Massachusetts
city: Bingham Farms
country: United States
facility: QUEST Research Institute
state: Michigan
city: Traverse City
country: United States
facility: Medical Research Associates, Inc.
state: Michigan
city: Hazelwood
country: United States
facility: Healthcare Research Network
state: Missouri
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: Albuquerque Clinical Trials, Inc.
state: New Mexico
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: 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: 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: Greer
country: United States
facility: Radiant Research, Inc.
state: South Carolina
city: Rapid City
country: United States
facility: Health Concepts
state: South Dakota
city: Hendersonville
country: United States
facility: Comprehensive Pain Specialists, LLC
state: Tennessee
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: Dallas
country: United States
facility: KRK Medical Research
state: Texas
city: Houston
country: United States
facility: Heights Doctor's Clinic
state: Texas
city: Lake Jackson
country: United States
facility: R/D Clinical Research, Inc.
state: Texas
city: San Antonio
country: United States
facility: Sun Research Institute
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, Sitar S, Lynch SY, He E, Ripa SR. A multicenter, randomized, double-blind, placebo-controlled trial to assess the efficacy and safety of single-entity, once-daily hydrocodone tablets in patients with uncontrolled moderate to severe chronic low back pain. Expert Opin Pharmacother. 2015;16(11):1593-606. doi: 10.1517/14656566.2015.1060221. Epub 2015 Jun 26.
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.