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

NCT ID: NCT01240863

Last Updated: 2017-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 391 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-30
• Study Completion Date: 2011-08-31

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.

Detailed Description

The study consisted of a screening period of approximately 7 to 14 days, an open label titration period of up to 6 weeks, and a double blind treatment period of 12 weeks.

Participants entered the open label titration period and received hydrocodone ER tablets beginning with 15 mg every 12 hours for 3 to 7 days. The objective of the open label titration period was to find the successful dose of hydrocodone ER tablets that produced stable pain relief (defined as an Average Pain Intensity (API) score of 4 or less on the 11-point numerical rating scale for either 3 consecutive days or 3 out of 5 consecutive days while the patient was maintained on the same dose of study drug for up to 7 days). Patients returned to the study center prior to each dose adjustment.

Participants who met the criterion of a stabilized dose were randomly assigned into the 12 week, double blind, placebo controlled treatment period on the final day of the open label titration period (baseline visit). Patients began treatment with double blind study drug at the effective dose of hydrocodone ER tablets achieved during the titration period or matching placebo. Rescue medication was permitted in addition to the study drug during the double blind treatment period.

Conditions

Chronic Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Hydrocodone ER

Intervention Type: 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.

Placebo

Intervention Type: 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.

Hydrocodone ER

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.

Group Type: EXPERIMENTAL

Hydrocodone ER

Intervention Type: 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.

Interventions

Hydrocodone ER

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

CEP-33237; Hydrocodone bitartrate extended-release

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• The patient is involved in active litigation in regard to the pain currently being treated.
• The patient has a positive urine drug screen (UDS) that is not medically explainable.
• The investigator feels that the patient is not suitable for the study for any reason.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Teva Branded Pharmaceutical Products R&D, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sponsor's Medical Expert, MD

Role: STUDY_DIRECTOR

Cephalon

Locations

Horizon Research Group LLC

Mobile, Alabama, United States

Radiant Research, Inc.

Chandler, Arizona, United States

Radiant Research, Inc.

Scottsdale, Arizona, United States

Radiant Research Inc.

Tucson, Arizona, United States

Physician Alliance Research Center

Anaheim, California, United States

Associated Pharmaceutical Research Center, Inc.

Buena Park, California, United States

Providence Clinical Research

Burbank, California, United States

Synergy Clinical Research

Escondido, California, United States

Research Center of Fresno, Inc.

Fresno, California, United States

Pacific Coast Pain Management Center

Laguna Hills, California, United States

South Orange County Surgical Medical Group

Laguna Hills, California, United States

Robert M. Karns, MD A Medical Corporation

Los Angeles, California, United States

Accelovance, Inc.

San Diego, California, United States

Radiant Research, Inc.

Santa Rosa, California, United States

Bayview Research Group, LLC

Valley Village, California, United States

Radiant Research, Inc

Denver, Colorado, United States

Clinical Research of West Florida, Inc.

Clearwater, Florida, United States

Avail Clinical Research, LLC

DeLand, Florida, United States

International Research Associates, LLC

Miami, Florida, United States

Compass Research

Orlando, Florida, United States

Radiant Research, Inc.

Pinellas Park, Florida, United States

Gold Coast Research LLC

Plantation, Florida, United States

Sarasota Pain Medicine Research LLC

Sarasota, Florida, United States

Clinical Research of West Florida, Inc.

Tampa, Florida, United States

Drug Studies America

Marietta, Georgia, United States

Georgia Institute for Clinical Research, LLC

Marietta, Georgia, United States

Better Health Clinical Research, Inc.

Newnan, Georgia, United States

Millennium Pain Center

Bloomington, Illinois, United States

Medex Healthcare Research, Inc.

Chicago, Illinois, United States

Rehabilitation Associates of Indiana

Indianapolis, Indiana, United States

International Clinical Research, Inc.

Leawood, Kansas, United States

Community Research

Crestview, Kentucky, United States

The Pain Treatment Center of the Bluegrass

Lexington, Kentucky, United States

Horizon Research Group, LLC

Baton Rouge, Louisiana, United States

WK River Cities Clinical Research Center

Shreveport, Louisiana, United States

MidAtlantic Pain Medicine Center

Pikesville, Maryland, United States

Beacon Clinical Research, LLC

Brockton, Massachusetts, United States

HealthCare Research

Florissant, Missouri, United States

Medex Healthcare Research Inc.

St Louis, Missouri, United States

Sundance Clinical Research, LLC

St Louis, Missouri, United States

Meridian Clinical Research

Omaha, Nebraska, United States

Clinical Research Center of Nevada

Las Vegas, Nevada, United States

Advanced Pain Consultants

Voorhees Township, New Jersey, United States

Upstate Clinical Research Associates

Williamsville, New York, United States

Wake Research Associates

Raleigh, North Carolina, United States

Radiant Research, Inc

Akron, Ohio, United States

Sterling Research Group, Ltd.

Cincinnati, Ohio, United States

Community Research, Inc

Cincinnati, Ohio, United States

Community Research, Inc

Cincinnati, Ohio, United States

Rapid Medical Research

Cleveland, Ohio, United States

Columbus Clinical Research

Columbus, Ohio, United States

SP Research

Oklahoma City, Oklahoma, United States

Pain Research of Oregon

Eugene, Oregon, United States

Summit Research Network Inc.

Portland, Oregon, United States

Brandywine Clinical Research

Downingtown, Pennsylvania, United States

Tipton Medical and Diagnostic Center

Tipton, Pennsylvania, United States

AMH Feasterville Family Health Care Center

Trevose, Pennsylvania, United States

Clinical Research Center of Reading

Wyomissing, Pennsylvania, United States

Omega Medical Research

Warwick, Rhode Island, United States

Radiant Research Inc.

Anderson, South Carolina, United States

Greenville Pharmaceutical Research

Greenville, South Carolina, United States

Radiant Research, Inc

Greer, South Carolina, United States

Trident Institute of Medical Research, LLC

North Charleston, South Carolina, United States

South Carolina Pharmaceutical Research

Spartanburg, South Carolina, United States

KRK Medical Research

Dallas, Texas, United States

Radiant Research Dallas

Dallas, Texas, United States

Renaissance Clinical Research & Hypertension of Texas, PLLC

Dallas, Texas, United States

Medstar Clinical Research

Houston, Texas, United States

Benchmark Research

San Angelo, Texas, United States

DCT-Sugarland, LLC

Sugar Land, Texas, United States

Hillcrest Family Health Centers

Waco, Texas, United States

Aspen Clinical Research, LLC

Orem, Utah, United States

Lifetree Clinical Research

Salt Lake City, Utah, United States

Countries

United States

Other Identifiers

C33237/3079

Identifier Type: -

Identifier Source: org_study_id