Study to Evaluate the Efficacy and Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) for Relief of Moderate to Severe Pain in Patients With Osteoarthritis or Low Back Pain Who Require Opioid Treatment for an Extended Period of Time

NCT01240863 | Completed Phase 3 Results

• 1 other identifier: C33237/3079
• Study Type: interventional
• Target: 391
• Locations: 1 country
• Sites: 73

Brief Summary

The primary objective of this study is to evaluate efficacy of hydrocodone extended-release (ER) tablets compared with placebo in alleviating moderate to severe pain in patients with osteoarthritis or low back pain as assessed by the weekly Average Pain Intensity (API) at week 12.

Conditions

Chronic Pain

Keywords

osteoarthritis; low back pain; Moderate to Severe Pain

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 12 in Weekly Average Pain Intensity (wAPI)

  The primary efficacy variable was the change from baseline to week 12 in the wAPI. The API over the previous 24 hours, based on the 11-point Numerical Rating Scale (NRS 11), was collected daily by e-diary. The Week 12 wAPI scores from the previous 7 days were calculated for each study visit and averaged. The baseline wAPI score was calculated by averaging API scores from 3 to 12 days when the successful dose of hydrocodone extended release was confirmed at the end of the open label titration period, before patients were randomly assigned study drug. In the case of missing week-12 data due to early withdrawal from the study, or excessive rescue medication usage, the wAPI for week 12 was imputed. The Numeric Rating Scale (NRS-11) is an 11-point scale for patient self-reporting of pain on a Likert-type scale in which 0 is no pain and 10 is the worst pain imaginable. Negative change from baseline values indicate lessening in pain intensity.

  Baseline (end of Open-Label Titration Period), Week 12 of Double-blind Treatment Period

Secondary Outcomes (25)

• Percentage of Participants Withdrawn From the Study During the Double-Blind Treatment Period By Reason

  Day 1 to Week 12 of the double-blind treatment period

• Kaplan-Meier Estimates for Time to Discontinuation From the Study

  Day 1 to Week 12 of the double-blind treatment period

• Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 33%

  Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period

• Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 50%

  Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period

• Weekly Average Pain Intensity (wAPI) Scores During the Double-blind Treatment Period

  Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours at the dosage deemed successful for managing their pain during the titration period. During the treatment period, participants were administered placebo tablets every 12 hours that matched the dosage deemed successful for managing their pain during the titration period. A step-wise, double-blind schedule to tamper off active drug was implemented during the first 2 weeks of the 12-week, double-blind, placebo-controlled treatment period to reduce the risk of withdrawal effects in participants randomly assigned to placebo.

Drug: Hydrocodone ER; Drug: Placebo

Hydrocodone ER

EXPERIMENTAL

Participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours at the dosage deemed successful for managing their pain during the titration period. During the 12-week, double-blind, placebo-controlled treatment period, participants randomly assigned to hydrocodone ER were administered tablets every 12 hours at the dosage deemed successful for managing their pain during the titration period.

Drug: Hydrocodone ER

Interventions

Hydrocodone ER DRUG

During the open-label, titration period, all participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours to identify a dosage deemed successful for managing their pain. Hydrocodone ER was taken by participants randomized to the hydrocodone ER treatment arm during the double-blind treatment period at the dose level identified during the titration period. Participants were instructed to take tablets with a glass of water on an empty stomach at least 1 hour before or 2 hours after eating.

Also known as: CEP-33237, Hydrocodone bitartrate extended-release

Hydrocodone ER; Placebo

Placebo DRUG

Placebo matching the active drug dose identified during the titration period was taken by participants randomized to the placebo treatment arm during the double-blind treatment period. Participants were instructed to take intervention with a glass of water on an empty stomach at least 1 hour before or 2 hours after eating.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient is able to speak English and is willing to provide written informed consent, including a written opioid agreement, to participate in this study.
• The patient must be willing and able to successfully self-administer the study drug, comply with study restrictions, complete the electronic diary, and return to the clinic for scheduled study visits as specified in this protocol.
• Women of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study, and have a negative pregnancy test at screening.
• The patient has pain of at least 3 months' duration associated with osteoarthritis or low back pain.
• The patient reports an average pain intensity score, over the prior 24 hours, of 5 or more on the 11-point numerical rating scale.
• If the patient is receiving physical therapy, biofeedback therapy, acupuncture therapy, or herbal remedies, these therapies must remain unchanged during the study.
• The patient must not participate in other study involving an investigational agent while enrolled into the present study.

You may not qualify if:

• The patient has known or suspected hypersensitivities, allergies, or other contraindications to any ingredient in the study drug.
• The patient has a recent history (within 5 years) or current evidence of alcohol or other substance abuse with the exception of nicotine or caffeine.
• The patient has medical or psychiatric disease that, in the opinion of the investigator, would compromise collected data.
• The patient is taking a total (ie, around-the-clock plus rescue medication) of more than 135 mg/day of oxycodone, or equivalent, during the 14 days prior to screening.
• The patient has a history of suicidality.
• The patient is expected to have surgery during the study.
• The patient's primary painful condition under study is related to any source of chronic pain other than osteoarthritis or low back pain.
• The patient is pregnant or lactating.
• The patient has active malignancy.
• The patient has human immunodeficiency virus (HIV).
• In the judgment of the investigator, the patient has any clinically significant deviation from normal in the physical examination and/or clinical laboratory test values.
• The patient has cardiopulmonary disease that would, in the opinion of the investigator, significantly increase the risk of treatment with opioids.
• The patient has participated in a study involving an investigational drug in the previous 30 days.
• The patient has received a monoamine oxidase inhibitor (MAOI) within 14 days before the first treatment with study drug.
• The patient has any other medical condition or is receiving concomitant medication/therapy (e.g., regional nerve block) that would, in the opinion of the investigator, compromise the patient's safety or compliance with the study protocol, or compromise collected data.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (73)

Horizon Research Group LLC

Mobile, Alabama, 36608, United States

Location

Radiant Research, Inc.

Chandler, Arizona, 85225, United States

Location

Radiant Research, Inc.

Scottsdale, Arizona, 85251, United States

Location

Radiant Research Inc.

Tucson, Arizona, 85710, United States

Location

Physician Alliance Research Center

Anaheim, California, 92804, United States

Location

Associated Pharmaceutical Research Center, Inc.

Buena Park, California, 90620, United States

Location

Providence Clinical Research

Burbank, California, 91505, United States

Location

Synergy Clinical Research

Escondido, California, 92025, United States

Location

Research Center of Fresno, Inc.

Fresno, California, 93726, United States

Location

Pacific Coast Pain Management Center

Laguna Hills, California, 92637, United States

Location

South Orange County Surgical Medical Group

Laguna Hills, California, 92653, United States

Location

Robert M. Karns, MD A Medical Corporation

Los Angeles, California, 90036, United States

Location

Accelovance, Inc.

San Diego, California, 92108, United States

Location

Radiant Research, Inc.

Santa Rosa, California, 95405, United States

Location

Bayview Research Group, LLC

Valley Village, California, 91607, United States

Location

Radiant Research, Inc

Denver, Colorado, 80239, United States

Location

Clinical Research of West Florida, Inc.

Clearwater, Florida, 33765, United States

Location

Avail Clinical Research, LLC

DeLand, Florida, 32720, United States

Location

International Research Associates, LLC

Miami, Florida, 33183, United States

Location

Compass Research

Orlando, Florida, 32806, United States

Location

Radiant Research, Inc.

Pinellas Park, Florida, 33781, United States

Location

Gold Coast Research LLC

Plantation, Florida, 33317, United States

Location

Sarasota Pain Medicine Research LLC

Sarasota, Florida, 34238, United States

Location

Clinical Research of West Florida, Inc.

Tampa, Florida, 33603, United States

Location

Drug Studies America

Marietta, Georgia, 30060, United States

Location

Georgia Institute for Clinical Research, LLC

Marietta, Georgia, 30060, United States

Location

Better Health Clinical Research, Inc.

Newnan, Georgia, 30265, United States

Location

Millennium Pain Center

Bloomington, Illinois, 61701, United States

Location

Medex Healthcare Research, Inc.

Chicago, Illinois, 60603, United States

Location

Rehabilitation Associates of Indiana

Indianapolis, Indiana, 46250, United States

Location

International Clinical Research, Inc.

Leawood, Kansas, 66211, United States

Location

Community Research

Crestview, Kentucky, 41017, United States

Location

The Pain Treatment Center of the Bluegrass

Lexington, Kentucky, 40503, United States

Location

Horizon Research Group, LLC

Baton Rouge, Louisiana, 70809, United States

Location

WK River Cities Clinical Research Center

Shreveport, Louisiana, 71105, United States

Location

MidAtlantic Pain Medicine Center

Pikesville, Maryland, 21208, United States

Location

Beacon Clinical Research, LLC

Brockton, Massachusetts, 02301, United States

Location

HealthCare Research

Florissant, Missouri, 63031, United States

Location

Medex Healthcare Research Inc.

St Louis, Missouri, 63117, United States

Location

Sundance Clinical Research, LLC

St Louis, Missouri, 63141, United States

Location

Meridian Clinical Research

Omaha, Nebraska, 68134, United States

Location

Clinical Research Center of Nevada

Las Vegas, Nevada, 89104, United States

Location

Advanced Pain Consultants

Voorhees Township, New Jersey, 08043, United States

Location

Upstate Clinical Research Associates

Williamsville, New York, 14221, United States

Location

Wake Research Associates

Raleigh, North Carolina, 27612, United States

Location

Radiant Research, Inc

Akron, Ohio, 44311, United States

Location

Sterling Research Group, Ltd.

Cincinnati, Ohio, 45219, United States

Location

Community Research, Inc

Cincinnati, Ohio, 45227, United States

Location

Community Research, Inc

Cincinnati, Ohio, 45245, United States

Location

Rapid Medical Research

Cleveland, Ohio, 44122, United States

Location

Columbus Clinical Research

Columbus, Ohio, 43213, United States

Location

SP Research

Oklahoma City, Oklahoma, 73112, United States

Location

Pain Research of Oregon

Eugene, Oregon, 97401, United States

Location

Summit Research Network Inc.

Portland, Oregon, 97210, United States

Location

Brandywine Clinical Research

Downingtown, Pennsylvania, 19335, United States

Location

Tipton Medical and Diagnostic Center

Tipton, Pennsylvania, 16684, United States

Location

AMH Feasterville Family Health Care Center

Trevose, Pennsylvania, 19053, United States

Location

Clinical Research Center of Reading

Wyomissing, Pennsylvania, 19610, United States

Location

Omega Medical Research

Warwick, Rhode Island, 02886, United States

Location

Radiant Research Inc.

Anderson, South Carolina, 29621, United States

Location

Greenville Pharmaceutical Research

Greenville, South Carolina, 29615, United States

Location

Radiant Research, Inc

Greer, South Carolina, 29651, United States

Location

Trident Institute of Medical Research, LLC

North Charleston, South Carolina, 29406, United States

Location

South Carolina Pharmaceutical Research

Spartanburg, South Carolina, 29303, United States

Location

KRK Medical Research

Dallas, Texas, 75230, United States

Location

Radiant Research Dallas

Dallas, Texas, 75231, United States

Location

Renaissance Clinical Research & Hypertension of Texas, PLLC

Dallas, Texas, 75235, United States

Location

Medstar Clinical Research

Houston, Texas, 77083, United States

Location

Benchmark Research

San Angelo, Texas, 76904, United States

Location

DCT-Sugarland, LLC

Sugar Land, Texas, 77478, United States

Location

Hillcrest Family Health Centers

Waco, Texas, 76710, United States

Location

Aspen Clinical Research, LLC

Orem, Utah, 84058, United States

Location

Lifetree Clinical Research

Salt Lake City, Utah, 84106, United States

Location

MeSH Terms

Conditions

Chronic Pain; Osteoarthritis; Low Back Pain

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Back Pain

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc

ustevatrials@tevapharm.com

215-591-3000

Study Officials

• Sponsor's Medical Expert, MD

  Cephalon

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2010
• First Posted: November 15, 2010
• Study Start: November 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: August 1, 2011
• Last Updated: June 5, 2017
• Results First Posted: June 5, 2017

Record last verified: 2017-06

Locations

US (73)