Clinical trial NCT01223365: Study to Evaluate the Long-Term Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) in Patients Who Require Opioid Treatment for an Extended Period of Time
Official title: A 12-Month, Open-Label Study to Evaluate the Long-Term Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) at 15 to 90 mg Every 12 Hours in Patients Who Require Opioid Treatment for an Extended Period of Time
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Pain
Keywords: moderate to severe pain
diabetic peripheral neuropathy
postherpetic neuralgia
traumatic injury
complex regional pain syndrome
back pain
neck pain
osteoarthritis
rheumatoid arthritis
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2010-10-19
Enrollment: 330
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety of hydrocodone extended-release tablets when used over a 12-month period in patients with chronic pain, as assessed by adverse events, clinical laboratory results, vital signs measurements, electrocardiogram results, physical examination findings, pure tone audiometry, and concomitant medication usage.

Detailed description: This was a Phase 3, open-label, nonrandomized study that consisted of a screening period, an open label titration period, and a 52 week, long term, open-label treatment period in patients with chronic pain. Patients were eligible to participate in this study if they had completed study C33237/3079 (NCT01240863) (these patients are hereafter referred to as rollover patients) or if they had not participated in study 3079 (these patients are hereafter referred to as either new opioid naïve or new opioid experienced patients).

Eligibility criteria: Inclusion Criteria:

* The patient must be willing and able to successfully self-administer the study drug, comply with study restrictions, and return to the clinic for scheduled study visits as specified in this protocol.
* The patient has either completed Cephalon study 3079 or has chronic pain of at least 3 months duration prior to entering this study associated with any of the following conditions: diabetic peripheral neuropathy, postherpetic neuralgia, traumatic injury, complex regional pain syndrome, back pain, neck pain, osteoarthritis, or rheumatoid arthritis. Patients with other painful conditions may qualify for the study with permission from the Cephalon medical monitor or designee.
* Those patients who completed the 12-week, double-blind, placebo-controlled, randomized study (study 3079) and are willing to re-titrate study drug to an effective dose of hydrocodone extended-release tablets are eligible to enter this study.
* The patient is able to speak English, willing to provide written informed consent, and sign a written opioid agreement, to participate in this study.
* The patient is 18 through 80 years of age (inclusive) at the time of entering this or the previous study (study 3079).
* 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.

Exclusion Criteria:

* Patients who were enrolled in study 3079 but did not complete the 12-week, double-blind, placebo-controlled, randomized study may not be enrolled into this study.
* The patient has known or suspected hypersensitivities, allergies, or other contraindications to the study drug or its excipients.
* The patient has a recent history (within 5 years) or current evidence of alcohol or other substance abuse.
* The patient has a medical or psychiatric condition/disease that, in the opinion of the investigator, would compromise collected data.
* The patient is taking a total (i.e., including around-the clock \[ATC\] and rescue medications) of more than 135 mg/day of oxycodone or equivalent for 14 days prior to screening.
* The patient has a history of suicidality.
* The patient has a diagnosis of chronic headache or migraine as the primary painful condition under study.
* The patient is expected to have surgery during the study and it is anticipated that the surgery will alleviate the patient's 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 potent synthetic opioids.
* The patient has participated in a study involving an investigational drug in the previous 30 days (excluding those who participated in study 3079).
* 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 chronic pain currently being treated.
* The patient has a positive urine drug screen (UDS) for an illicit substance or medication not prescribed by the physician currently treating the chronic pain.
* The investigator feels that the patient is not suitable for the study.

Primary outcomes:
measure: Participants With Adverse Experiences
timeFrame: Day 1 of open-label titration period - Week 52 of the open-label treatment period
measure: Participants With Potentially Clinically Significant (PCS) Abnormal Laboratory Values During the Open-Label Treatment Period by Participant Status
timeFrame: Day 1 - Week 52 of the open-label treatment period
measure: Participants With Potentially Clinically Significant Abnormal Vital Signs Values by Participant Status
timeFrame: Day 1 of open-label titration period - Week 52 of the open-label treatment period
measure: Shifts in Electrocardiogram (ECG) Findings From Baseline to Overall Study by Participant Status
timeFrame: Baseline for new participants was between Day -7 and -14 (the study 3080 screening visit); baseline for rollover participants was the last ECG in study 3079. During study ECGs were performed on weeks 24 and 52 of the open-label treatment period
measure: Participants With Clinically Significant (CS) Hearing Changes From Baseline in Pure Tone Audiometry Test Results by Patient Status
timeFrame: Baseline for new participants was between Day -7 and -14 (study 3080 screening visit); baseline for rollover participants was the baseline test in study 3079. During study covers both open-label titration and 52-week treatment periods
Secondary outcomes:
measure: Participant Global Assessment (PGA) of the Method of Pain Control by Participant Status
timeFrame: Baseline for new participants was Day 1, i.e. the first day of open-label titration. Baseline for rollover participants was the baseline in study 3079. Week 4 (end of titration, start of open-label treatment), Week 52, last visit up to Week 52
measure: Participants by Risk Category for Aberrant Drug Misuse Based on the Total Score in the Screener and Opioid Assessment for Patients With Pain - Revised (SOAPP-R)
timeFrame: End of Open-label Titration Period. Weeks 4 and 24 of the Open-label Treatment Period
measure: Addiction Behavior Checklist (ABC) Total Scores During Both the Open-Label Titration and Open-Label Treatment Periods by Participant Status
timeFrame: Baseline for new participants was Day 1 of open-label titration; rollover participants baseline was in study 3079. End of Open-label Titration: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 40, 44, 48, 52 and last visit up to week 52
measure: Current Opioid Misuse Measure (COMM) Scores During Both the Open-Label Titration and Open-Label Treatment Periods by Participant Status
timeFrame: Baseline for new participants was Day 1 of open-label titration; rollover participants baseline was in study 3079. End of Open-label Titration Period. Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36 40, 44, 48, 52 and last visit up to week 52
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Horizon Research Group, LLC
state: Alabama
city: Anaheim
country: United States
facility: Physician Alliance Research Center
state: California
city: Beverly Hills
country: United States
facility: Adam D. Karns, MD
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: 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: San Diego
country: United States
facility: Accelovance, Inc.
state: California
city: Valley Village
country: United States
facility: Bayview Research Group, LLC
state: California
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: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Sarasota
country: United States
facility: Sarasota Pain Medicine Research LLC
state: Florida
city: Weston
country: United States
facility: Gold Coast Research LLC
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: Marietta
country: United States
facility: Taylor 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: Indianapolis
country: United States
facility: Rehabilitation Associates of Indiana
state: Indiana
city: Overland Park
country: United States
facility: International Clinical Research, Inc.
state: Kansas
city: Crestview Hills
country: United States
facility: Community Research
state: Kentucky
city: Shreveport
country: United States
facility: Willis Knighton 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: 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: Cincinnati
country: United States
facility: Sterling Research Group, Ltd.
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: Feasterville-Trevose
country: United States
facility: AMH Feasterville Family Health Care Center
state: Pennsylvania
city: Tipton
country: United States
facility: Tipton Medical and Diagnostic Center
state: Pennsylvania
city: West Reading
country: United States
facility: Clinical Research Center of Reading, LLP
state: Pennsylvania
city: Warwick
country: United States
facility: Omega Medical Research
state: Rhode Island
city: Greenville
country: United States
facility: Greenville Pharmaceutical Research
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: S. 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
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 dba Discovery Clinical Trials
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
Study officials:
affiliation: Cephalon
name: Sponsor's Medical Expert, MD
role: STUDY_DIRECTOR
References: