Clinical trial NCT01240863: 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
Official title: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) at 15 to 90 mg Every 12 Hours 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Pain
Keywords: osteoarthritis
low back pain
Moderate to Severe Pain
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2010-11-15
Enrollment: 391
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
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 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.

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.

Primary outcomes:
measure: Change From Baseline to Week 12 in Weekly Average Pain Intensity (wAPI)
timeFrame: Baseline (end of Open-Label Titration Period), Week 12 of Double-blind Treatment Period
Secondary outcomes:
measure: Percentage of Participants Withdrawn From the Study During the Double-Blind Treatment Period By Reason
timeFrame: Day 1 to Week 12 of the double-blind treatment period
measure: Kaplan-Meier Estimates for Time to Discontinuation From the Study
timeFrame: Day 1 to Week 12 of the double-blind treatment period
measure: Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 33%
timeFrame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
measure: Participants With a Weekly Average Pain Intensity (wAPI) Increase From Baseline Exceeding 50%
timeFrame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
measure: Weekly Average Pain Intensity (wAPI) Scores During the Double-blind Treatment Period
timeFrame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
measure: Weekly Average Worst Pain Intensity (WPI) Scores During the Double-blind Treatment Period
timeFrame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
measure: Clinician Assessment of Patient Function (CAPF) at Week 4
timeFrame: Week 4 of the Double-blind Treatment Period
measure: Clinician Assessment of Patient Function (CAPF) at Week 8
timeFrame: Week 8 of the Double-blind Treatment Period
measure: Clinician Assessment of Patient Function (CAPF) at Week 12
timeFrame: Week 12 of the Double-blind Treatment Period
measure: Clinician Assessment of Patient Function (CAPF) at Endpoint
timeFrame: Endpoint of the Double-blind Treatment Period (up to week 12)
measure: Patient Assessment of Function (PAF) at Week 4
timeFrame: Week 4 of the Double-blind Treatment Period
measure: Patient Assessment of Function (PAF) at Week 8
timeFrame: Week 8 of the Double-blind Treatment Period
measure: Patient Assessment of Function (PAF) at Week 12
timeFrame: Week 12 of the Double-blind Treatment Period
measure: Patient Assessment of Function (PAF) at Endpoint
timeFrame: Endpoint of the Double-blind Treatment Period (up to week 12)
measure: Clinician Global Impression of Severity (CGI-S) of Illness Scores During the Double-blind Treatment Period
timeFrame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, and 12 of the Double-blind treatment period
measure: Short-Form Health Survey (SF-36) Physical and Mental Component Summary Scores at Baseline, Week 12 and Endpoint
timeFrame: Baseline (end of Open-Label Titration Period), Week 12 and Endpoint (last visit up to week 12) of the Double-blind treatment period
measure: Brief Pain Inventory - Short Form (BPI-SF) Pain Interference Mean Score During the Double-Blind Treatment Period
timeFrame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to week 12) of the Double-blind treatment period
measure: Participants With Adverse Events
timeFrame: Day 1 up to Day 52 in Open-Label Titration; Day 1 up to Day 128 in Double-Blind Treatment period
measure: Participants With Potentially Clinically Significant Abnormal Vital Signs Values During the Double-Blind Treatment Period
timeFrame: Day 1 up to Day 128 in Double-Blind Treatment period
measure: Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period
timeFrame: Day 1 up to Day 128 in Double-Blind Treatment period
measure: Subjective Opiate Withdrawal Scales (SOWS) Scores During the Double-Blind Treatment Period
timeFrame: Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to Week 12) of the Double-blind treatment period
measure: Clinical Opiate Withdrawal Scales (COWS) Scores During the Double-Blind Treatment Period
timeFrame: Baseline (end of Open-Label Titration Period), Weeks 1, 2, 4, 8, 12 and Endpoint (last visit up to Week 12) of the Double-blind treatment period
measure: Addiction Behavior Checklist (ABC) Total Scores During Both the Open-Label Titration and Double-Blind Treatment Periods
timeFrame: Baseline for Open-Label Titration period, Baseline for Double-Blind Treatment period (which is also the end of the Open-Label Titration period), Weeks 1, 4, 8, 12, and Endpoint (last visit up to Week 12) of the Double-blind Treatment period
measure: Current Opioid Misuse Measures (COMM) Total Scores During Both the Open-Label Titration and Double-Blind Treatment Periods
timeFrame: Baseline for Open-Label Titration period, Baseline for Double-Blind Treatment period (which is also the end of the Open-Label Titration period), Weeks 1, 4, 8, 12, and Endpoint (last visit up to Week 12) of the Double-blind Treatment period
measure: Change From Baseline to Endpoint in the Double-Blind Treatment Phase in Electrocardiogram (ECG) Parameters
timeFrame: Baseline (end of Open-Label Titration Period), Endpoint (last visit up to Week 12) of the Double-blind treatment period
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Horizon Research Group LLC
state: Alabama
city: Chandler
country: United States
facility: Radiant Research, Inc.
state: Arizona
city: Scottsdale
country: United States
facility: Radiant Research, Inc.
state: Arizona
city: Tucson
country: United States
facility: Radiant Research Inc.
state: Arizona
city: Anaheim
country: United States
facility: Physician Alliance Research Center
state: California
city: Buena Park
country: United States
facility: Associated Pharmaceutical Research Center, Inc.
state: California
city: Burbank
country: United States
facility: Providence Clinical Research
state: California
city: Escondido
country: United States
facility: Synergy Clinical Research
state: California
city: Fresno
country: United States
facility: Research Center of Fresno, Inc.
state: California
city: Laguna Hills
country: United States
facility: Pacific Coast Pain Management Center
state: California
city: Laguna Hills
country: United States
facility: South Orange County Surgical Medical Group
state: California
city: Los Angeles
country: United States
facility: Robert M. Karns, MD A Medical Corporation
state: California
city: San Diego
country: United States
facility: Accelovance, Inc.
state: California
city: Santa Rosa
country: United States
facility: Radiant Research, Inc.
state: California
city: Valley Village
country: United States
facility: Bayview Research Group, LLC
state: California
city: Denver
country: United States
facility: Radiant Research, Inc
state: Colorado
city: Clearwater
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Miami
country: United States
facility: International Research Associates, LLC
state: Florida
city: Orlando
country: United States
facility: Compass Research
state: Florida
city: Pinellas Park
country: United States
facility: Radiant Research, Inc.
state: Florida
city: Plantation
country: United States
facility: Gold Coast Research LLC
state: Florida
city: Sarasota
country: United States
facility: Sarasota Pain Medicine Research LLC
state: Florida
city: Tampa
country: United States
facility: Clinical Research of West Florida, Inc.
state: Florida
city: Marietta
country: United States
facility: Drug Studies America
state: Georgia
city: Marietta
country: United States
facility: Georgia Institute for Clinical Research, LLC
state: Georgia
city: Newnan
country: United States
facility: Better Health Clinical Research, Inc.
state: Georgia
city: Bloomington
country: United States
facility: Millennium Pain Center
state: Illinois
city: Chicago
country: United States
facility: Medex Healthcare Research, Inc.
state: Illinois
city: Indianapolis
country: United States
facility: Rehabilitation Associates of Indiana
state: Indiana
city: Leawood
country: United States
facility: International Clinical Research, Inc.
state: Kansas
city: Crestview
country: United States
facility: Community Research
state: Kentucky
city: Lexington
country: United States
facility: The Pain Treatment Center of the Bluegrass
state: Kentucky
city: Baton Rouge
country: United States
facility: Horizon Research Group, LLC
state: Louisiana
city: Shreveport
country: United States
facility: WK River Cities Clinical Research Center
state: Louisiana
city: Pikesville
country: United States
facility: MidAtlantic Pain Medicine Center
state: Maryland
city: Brockton
country: United States
facility: Beacon Clinical Research, LLC
state: Massachusetts
city: Florissant
country: United States
facility: HealthCare Research
state: Missouri
city: Saint Louis
country: United States
facility: Medex Healthcare Research Inc.
state: Missouri
city: Saint Louis
country: United States
facility: Sundance Clinical Research, LLC
state: Missouri
city: Omaha
country: United States
facility: Meridian Clinical Research
state: Nebraska
city: Las Vegas
country: United States
facility: Clinical Research Center of Nevada
state: Nevada
city: Voorhees
country: United States
facility: Advanced Pain Consultants
state: New Jersey
city: Williamsville
country: United States
facility: Upstate Clinical Research Associates
state: New York
city: Raleigh
country: United States
facility: Wake Research Associates
state: North Carolina
city: Akron
country: United States
facility: Radiant Research, Inc
state: Ohio
city: Cincinnati
country: United States
facility: Sterling Research Group, Ltd.
state: Ohio
city: Cincinnati
country: United States
facility: Community Research, Inc
state: Ohio
city: Cincinnati
country: United States
facility: Community Research, Inc
state: Ohio
city: Cleveland
country: United States
facility: Rapid Medical Research
state: Ohio
city: Columbus
country: United States
facility: Columbus Clinical Research
state: Ohio
city: Oklahoma City
country: United States
facility: SP Research
state: Oklahoma
city: Eugene
country: United States
facility: Pain Research of Oregon
state: Oregon
city: Portland
country: United States
facility: Summit Research Network Inc.
state: Oregon
city: Downingtown
country: United States
facility: Brandywine Clinical Research
state: Pennsylvania
city: Tipton
country: United States
facility: Tipton Medical and Diagnostic Center
state: Pennsylvania
city: Trevose
country: United States
facility: AMH Feasterville Family Health Care Center
state: Pennsylvania
city: Wyomissing
country: United States
facility: Clinical Research Center of Reading
state: Pennsylvania
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Anderson
country: United States
facility: Radiant Research Inc.
state: South Carolina
city: Greenville
country: United States
facility: Greenville Pharmaceutical Research
state: South Carolina
city: Greer
country: United States
facility: Radiant Research, Inc
state: South Carolina
city: North Charleston
country: United States
facility: Trident Institute of Medical Research, LLC
state: South Carolina
city: Spartanburg
country: United States
facility: South Carolina Pharmaceutical Research
state: South Carolina
city: Dallas
country: United States
facility: KRK Medical Research
state: Texas
city: Dallas
country: United States
facility: Radiant Research Dallas
state: Texas
city: Dallas
country: United States
facility: Renaissance Clinical Research & Hypertension of Texas, PLLC
state: Texas
city: Houston
country: United States
facility: Medstar Clinical Research
state: Texas
city: San Angelo
country: United States
facility: Benchmark Research
state: Texas
city: Sugar Land
country: United States
facility: DCT-Sugarland, LLC
state: Texas
city: Waco
country: United States
facility: Hillcrest Family Health Centers
state: Texas
city: Orem
country: United States
facility: Aspen Clinical Research, LLC
state: Utah
city: Salt Lake City
country: United States
facility: Lifetree Clinical Research
state: Utah
Study officials:
affiliation: Cephalon
name: Sponsor's Medical Expert, MD
role: STUDY_DIRECTOR
References: