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

NCT01223365 | Completed Phase 3 Results

• 1 other identifier: C33237/3080
• Study Type: interventional
• Target: 330
• Locations: 1 country
• Sites: 54

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.

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

Outcome Measures

Primary Outcomes (5)

• Participants With Adverse Experiences

  An adverse event (AE) was defined in the protocol as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Relation of AE to treatment was determined by the investigator. Serious AEs include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.

  Day 1 of open-label titration period - Week 52 of the open-label treatment period

• Participants With Potentially Clinically Significant (PCS) Abnormal Laboratory Values During the Open-Label Treatment Period by Participant Status

  Data represents participants with PCS abnormal serum chemistry, hematology and urinalysis values. Significance criteria: * alanine aminotransferase (ALT): \>=3 times the upper limit of normal (ULN). Normal range is 6-43 U/L * aspartate aminotransferase (AST): \>=3 times ULN. Normal range is 9-36 U/L * blood urea nitrogen (BUN): \>=10.71 mmol/L * creatinine: \>=177 μmol/L * uric acid: M\>=625, F\>=506 μmol/L * white blood cell count: \<=3.0\*10\^9/L * hemoglobin: M\<=115, F\<=95 g/dL * hematocrit: M\<0.37, F\<0.32 L/L * urine blood (hemoglobin): \>=2 unit increase from baseline * urine glucose: \>=2 unit increase from baseline

  Day 1 - Week 52 of the open-label treatment period

• Participants With Potentially Clinically Significant Abnormal Vital Signs Values by Participant Status

  Data represents participants with potentially clinically significant (PCS) vital sign values. Significance criteria * Pulse - high: \>=120 and increase of \>= 15 beats/minute from baseline * Pulse - low: \<=50 and decrease of \>=15 beats/minute * Systolic blood pressure - high: \>=180 and increase \>=20 mmHg * Systolic blood pressure - low: \<=90 and decrease \>=20 mmHg * Diastolic blood pressure - high: \>=105 and increase of \>=15 mmHg * Diastolic blood pressure - low: \<=50 and decrease of \>=15 mmHg

  Day 1 of open-label titration period - Week 52 of the open-label treatment period

• Shifts in Electrocardiogram (ECG) Findings From Baseline to Overall Study by Participant Status

  A 12-lead ECG was conducted at screening, week 24, and week 52 or at the last postbaseline observation. For rollover participants, the ECG performed at the final visit of study 3079 served as the 1st ECG in study 3080. A qualified physician was responsible for interpreting the ECG. Any ECG finding that was judged by the investigator as a clinically meaningful change (worsening) compared with baseline was considered an adverse event. For overall results, the worst postbaseline finding for the participant was summarized. Results below are formatted as Baseline ECG result - Overall ECG result.

  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

• Participants With Clinically Significant (CS) Hearing Changes From Baseline in Pure Tone Audiometry Test Results by Patient Status

  Pure tone audiometry was performed by trained personnel. During the test, the patient wore headphones and was seated in a quiet room; trained personnel manipulated the audiometry equipment to test the patient's hearing. For serial audiograms, the criteria for a clinically significant (CS) hearing change were based on the guidance from the American Speech-Language Hearing Association (ASHA) 1994 (Konrad-Martin et al 2005). These criteria included the following: greater than 20 decibels (dB) pure tone threshold shift at 1 frequency; greater than 10 dB shift at 2 consecutive test frequencies; or threshold response shifting to "no response" at 3 consecutive test frequencies.

  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 (4)

• Participant Global Assessment (PGA) of the Method of Pain Control by Participant Status

  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

• 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)

  End of Open-label Titration Period. Weeks 4 and 24 of the Open-label Treatment Period

• Addiction Behavior Checklist (ABC) Total Scores During Both the Open-Label Titration and Open-Label Treatment Periods by Participant Status

  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

• Current Opioid Misuse Measure (COMM) Scores During Both the Open-Label Titration and Open-Label Treatment Periods by Participant Status

  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

Study Arms (1)

Hydrocodone ER

EXPERIMENTAL

Participants were titrated (or re-titrated for roll-over participants) at escalating dosages of extended-release hydrocodone tablets at dosages of 15, 30, 45, 60, or 90 mg orally every 12 hours until deemed successful for managing their pain during the open-label titration period. Once a successful dose was identified, participants entered the 52 week open-label treatment period in which hydrocodone ER was administered at the successful dose (15, 30, 45, 60, or 90 mg) every 12 hours.

Drug: Hydrocodone ER

Interventions

Hydrocodone ER DRUG

Hydrocodone bitartrate extended-release tablets were administered at doses of 15, 30, 45, 60, and 90 mg orally every 12 hours. During the open-label titration period, doses were adjusted until a stable pain control was achieved. In general, the dose of hydrocodone extended release tablets could be adjusted for efficacy or tolerability, as necessary, at any time during the open-label treatment period; however, participants were required to visit the study center before increasing the dose of study drug.

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

Hydrocodone ER

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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (54)

Horizon Research Group, LLC

Mobile, Alabama, United States

Location

Physician Alliance Research Center

Anaheim, California, United States

Location

Adam D. Karns, MD

Beverly Hills, California, United States

Location

Associated Pharmaceutical Research Center, Inc.

Buena Park, California, United States

Location

Providence Clinical Research

Burbank, California, United States

Location

Research Center of Fresno, Inc.

Fresno, California, United States

Location

Pacific Coast Pain Management Center

Laguna Hills, California, United States

Location

South Orange County Surgical Medical Group

Laguna Hills, California, United States

Location

Accelovance, Inc.

San Diego, California, United States

Location

Bayview Research Group, LLC

Valley Village, California, United States

Location

Clinical Research of West Florida, Inc.

Clearwater, Florida, United States

Location

Avail Clinical Research, LLC

DeLand, Florida, United States

Location

Compass Research, LLC

Orlando, Florida, United States

Location

Sarasota Pain Medicine Research LLC

Sarasota, Florida, United States

Location

Gold Coast Research LLC

Weston, Florida, United States

Location

Drug Studies America

Marietta, Georgia, United States

Location

Georgia Institute for Clinical Research, LLC

Marietta, Georgia, United States

Location

Taylor Research, LLC

Marietta, Georgia, United States

Location

Better Health Clinical Research, Inc.

Newnan, Georgia, United States

Location

Millennium Pain Center

Bloomington, Illinois, United States

Location

Rehabilitation Associates of Indiana

Indianapolis, Indiana, United States

Location

International Clinical Research, Inc.

Overland Park, Kansas, United States

Location

Community Research

Crestview Hills, Kentucky, United States

Location

Willis Knighton River Cities Clinical Research Center

Shreveport, Louisiana, United States

Location

MidAtlantic Pain Medicine Center

Pikesville, Maryland, United States

Location

Beacon Clinical Research, LLC

Brockton, Massachusetts, United States

Location

HealthCare Research

Florissant, Missouri, United States

Location

Sundance Clinical Research, LLC

St Louis, Missouri, United States

Location

Meridian Clinical Research

Omaha, Nebraska, United States

Location

Clinical Research Center of Nevada

Las Vegas, Nevada, United States

Location

Advanced Pain Consultants

Voorhees Township, New Jersey, United States

Location

Upstate Clinical Research Associates

Williamsville, New York, United States

Location

Wake Research Associates

Raleigh, North Carolina, United States

Location

Sterling Research Group, Ltd.

Cincinnati, Ohio, United States

Location

Columbus Clinical Research

Columbus, Ohio, United States

Location

SP Research

Oklahoma City, Oklahoma, United States

Location

Pain Research of Oregon

Eugene, Oregon, United States

Location

Summit Research Network Inc.

Portland, Oregon, United States

Location

Brandywine Clinical Research

Downingtown, Pennsylvania, United States

Location

AMH Feasterville Family Health Care Center

Feasterville-Trevose, Pennsylvania, United States

Location

Tipton Medical and Diagnostic Center

Tipton, Pennsylvania, United States

Location

Clinical Research Center of Reading, LLP

West Reading, Pennsylvania, United States

Location

Omega Medical Research

Warwick, Rhode Island, United States

Location

Greenville Pharmaceutical Research

Greenville, South Carolina, United States

Location

Trident Institute of Medical Research, LLC

North Charleston, South Carolina, United States

Location

S. Carolina Pharmaceutical Research

Spartanburg, South Carolina, United States

Location

KRK Medical Research

Dallas, Texas, United States

Location

Radiant Research

Dallas, Texas, United States

Location

Renaissance Clinical Research & Hypertension of Texas, PLLC

Dallas, Texas, United States

Location

Medstar Clinical Research

Houston, Texas, United States

Location

Benchmark Research

San Angelo, Texas, United States

Location

DCT-Sugarland, LLC dba Discovery Clinical Trials

Sugar Land, Texas, United States

Location

Hillcrest Family Health Centers

Waco, Texas, United States

Location

Aspen Clinical Research, LLC

Orem, Utah, United States

Location

MeSH Terms

Conditions

Chronic Pain; Neuralgia, Postherpetic; Wounds and Injuries; Complex Regional Pain Syndromes; Back Pain; Neck Pain; Osteoarthritis; Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neuralgia; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Autonomic Nervous System Diseases; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 15, 2010
• First Posted: October 19, 2010
• Study Start: October 1, 2010
• Primary Completion: September 1, 2012
• Study Completion: September 1, 2012
• Last Updated: June 5, 2017
• Results First Posted: April 5, 2017

Record last verified: 2017-05

Locations

US (54)