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

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Low Back Pain
• Intervention / Treatment: Drug: Hydrocodone bitartrate q24h film-coated tablets; Drug: Placebo to match hydrocodone bitartrate q24h tablets

• Study Type: Interventional
• Enrollment (Actual): 905
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35213
      • Alliance Clinical Research
    • Mobile, Alabama, United States, 36608
      • Coastal Clinical Research, Inc.
  • Arizona
    • Phoenix, Arizona, United States, 85029
      • Redpoint Research
    • Phoenix, Arizona, United States, 85023
      • Arizona Research Center
    • Tucson, Arizona, United States, 85712
      • Quality of Life Medical & Research Center, LLC
    • Tucson, Arizona, United States, 85704
      • Genova Clinical Research
    • Tucson, Arizona, United States, 85712
      • Redpoint Research
  • California
    • Anaheim, California, United States, 92804
      • United Clinical Research Center, Inc.
    • Anaheim, California, United States, 92801
      • Orange County Research Institute
    • Anaheim, California, United States, 92801-2417
      • ACRI-Phase 1, LLC
    • Fresno, California, United States, 93726
      • Research Center of Fresno, Inc.
    • La Mesa, California, United States, 91942
      • TriWest Research Associates
    • Lomita, California, United States, 90717
      • Torrance Clinical Research Institute Inc.
    • Long Beach, California, United States, 90806
      • Skyline Research, LLC
    • Richmond, California, United States, 94806
      • Center for Clinical Research, Inc.
    • Sacramento, California, United States, 95821
      • Northern California Research
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research, LLC
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • Orthopedic Research Institute
    • Bradenton, Florida, United States, 34208
      • Meridien Research
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • DeLand, Florida, United States, 32720
      • Avail Clinical Research, LLC
    • Fort Lauderdale, Florida, United States, 33312
      • Florida Health Center
    • Fort Myers, Florida, United States, 33916
      • Clinical Physiology Associates
    • Hialeah, Florida, United States, 33012
      • AGA Clinical Trials
    • Jacksonville, Florida, United States, 32216
      • Clinical Neuroscience Solutions, Inc.
    • Jupiter, Florida, United States, 33458
      • Health Awareness, Inc.
    • Lauderhill, Florida, United States, 33319
      • Fidelity Clinical Research, Inc.
    • Miami, Florida, United States, 33183
      • International Research Associates, LLC
    • Miami, Florida, United States, 33176
      • Neuroscience Consultants LLC
    • Oldsmar, Florida, United States, 34677
      • Journey Research, Inc
    • Orlando, Florida, United States, 32806
      • Compass Research, LLC
    • Orlando, Florida, United States, 32806
      • Clinical Neuroscience Solutions, Inc.
    • Ormond Beach, Florida, United States, 32174
      • Peninsula Research Inc.
    • Pinellas Park, Florida, United States, 33781
      • Advent Clinical Research Centers, Inc.
    • Plantation, Florida, United States, 33317
      • Gold Coast Research, LLC
    • Sarasota, Florida, United States, 34243
      • Sarasota Research, LLC
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida, Inc.
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Southeast Regional Research Group
    • Marietta, Georgia, United States, 30060
      • Georgia Institute for Clinical Research, LLC
    • Marietta, Georgia, United States, 30060
      • Taylor Research, LLC
    • Newnan, Georgia, United States, 30265
      • Better Health Clinical Research, Inc.
    • Stockbridge, Georgia, United States, 30281
      • Atlanta Knee and Shoulder Clinic, PC
  • Illinois
    • Chicago, Illinois, United States, 60622
      • Illinois Center for Clinical Research
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Rehabilitation Associates of Indiana
    • Valparaiso, Indiana, United States, 46383
      • Northwest Indiana Center for Clinical Research
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Integrated Clinical Trial Services, Inc.
  • Kansas
    • Overland Park, Kansas, United States, 66210
      • ICRI
  • Kentucky
    • Crestview Hills, Kentucky, United States, 41017
      • Community Research
    • Madisonville, Kentucky, United States, 42431
      • Commonwealth Biomedical Research, LLC
  • Louisiana
    • New Orleans, Louisiana, United States, 70114
      • Louisiana Research Associates, Inc.
  • Maryland
    • Towson, Maryland, United States, 21204
      • IRC Clinics, Inc.
  • Massachusetts
    • Brockton, Massachusetts, United States, 02301
      • Beacon Clinical Research, LLC
    • Watertown, Massachusetts, United States, 02472-3930
      • MedVadis Research Corporation
  • Michigan
    • Bingham Farms, Michigan, United States, 48025
      • Quest Research Institute
    • Traverse City, Michigan, United States, 49684
      • Medical Research Associates, Inc.
  • Missouri
    • Hazelwood, Missouri, United States, 63042
      • Healthcare Research Network
    • Saint Louis, Missouri, United States, 63141
      • Mercy Health Research
    • Saint Louis, Missouri, United States, 63117
      • Medex Healthcare Research, Inc.
    • Saint Louis, Missouri, United States, 63128
      • Advance Clinical Research
    • Saint Louis, Missouri, United States, 63141
      • Sundance Clinical Research, LLC
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Quality Clinical Research
  • Nevada
    • Las Vegas, Nevada, United States, 89123
      • Advanced Biomedical Research of America
    • Las Vegas, Nevada, United States, 89144
      • Research Facility
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Comprehensive Clinical Research
    • Willingboro, New Jersey, United States, 08046
      • CRI Worldwide LLC
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials, Inc.
    • Albuquerque, New Mexico, United States, 87108
      • Lovelace Scientific Resources
  • New York
    • Hartsdale, New York, United States, 10530
      • Drug Trials America
    • New York, New York, United States, 10128
      • The Medical Research Network, LLC
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • PMG Research of Charlotte, LLC
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington LLC
    • Winston-Salem, North Carolina, United States, 27103
      • Clinical Trials of America, Inc.
    • Winston-Salem, North Carolina, United States, 27103
      • The Center for Clinical Research
  • Ohio
    • Akron, Ohio, United States, 44313
      • DayStar Clinical Research, Inc.
    • Cincinnati, Ohio, United States, 45245
      • IVA Research
    • Cincinnati, Ohio, United States, 45255
      • Community Research
    • Toledo, Ohio, United States, 43623
      • Bone Joint and Spine Surgeons, Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73116
      • Cutting Edge Research Group
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16602
      • Allegheny Pain Management, P.C.
    • Philadelphia, Pennsylvania, United States, 19152
      • Founders Research Corporation
    • Philadelphia, Pennsylvania, United States, 19139
      • CRI Worldwide, LLC
    • Tipton, Pennsylvania, United States, 16684
      • Tipton Medical & Diagnostic Center
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • Hartwell Research Group
    • Greer, South Carolina, United States, 29651
      • Radiant Research, Inc.
  • South Dakota
    • Rapid City, South Dakota, United States, 57702
      • Health Concepts
  • Tennessee
    • Hendersonville, Tennessee, United States, 37075
      • Comprehensive Pain Specialists, LLC
    • Memphis, Tennessee, United States, 38119
      • Clinical Neuroscience Solutions, Inc.
    • New Tazewell, Tennessee, United States, 37825
      • Heartland Medical, PC
    • Smyrna, Tennessee, United States, 37167
      • HCCA Clinical Research Solutions
  • Texas
    • Austin, Texas, United States, 78731
      • FutureSearch Trials of Neurology
    • Dallas, Texas, United States, 75230
      • KRK Medical Research
    • Houston, Texas, United States, 77008
      • Heights Doctor's Clinic
    • Lake Jackson, Texas, United States, 77566
      • R/D Clinical Research, Inc.
    • San Antonio, Texas, United States, 78215
      • Sun Research Institute
  • Utah
    • Orem, Utah, United States, 84058
      • Aspen Clinical Research
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research
  • Virginia
    • Roanoke, Virginia, United States, 24018
      • HypotheTest, LLC
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center
    • Edmonds, Washington, United States, 98026
      • Washington Center for Pain Management

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Pain Intensity for "Average Pain Over the Last 24 Hours" Score	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).	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medical Outcome Study Sleep Scale - Revised (MOS Sleep-R) - Sleep Disturbance Subscale	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.	Weeks 4, 8, and 12
Patient Global Impression of Change (PGIC)	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.	Week 12
Responder Analysis for Subjects With a ≥ 30% Reduction in Pain Compared to Baseline	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.	Baseline to Week 12
Responder Analysis for Subjects With a ≥ 50% Reduction in Pain Compared to Baseline	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.	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Purdue Pharma LP

Publications and helpful links

General Publications

• 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.
• 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.

Helpful Links

• Full Prescribing Information

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): September 1, 2013
• Study Completion (ACTUAL): October 1, 2013

Study Registration Dates

• First Submitted: October 12, 2011
• First Submitted That Met QC Criteria: October 12, 2011
• First Posted (ESTIMATE): October 17, 2011

Study Record Updates

• Last Update Posted (ACTUAL): March 10, 2020
• Last Update Submitted That Met QC Criteria: March 2, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Pain; Opioid
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Hydrocodone
• Other Study ID Numbers: HYD3002