Clinical trial NCT01789970: Efficacy and Safety of Hydrocodone Bitartrate Extended-Release Tablets for Moderate to Severe Chronic Low Back Pain
Official title: A 12-Week, Randomized, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Study to Evaluate the Efficacy and Safety of Hydrocodone Bitartrate Extended-Release Tablets (CEP-33237) at 30 to 90 mg Every 12 Hours for Relief of Moderate to Severe Pain in Patients With Chronic Low Back Pain Who Require Opioid Treatment for an Extended Period of Time
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Low Back Pain
Keywords: chronic low back pain
hydrocodone bitartrate
opioids
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2013-02-12
Enrollment: 625
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 the efficacy of hydrocodone bitartrate extended-release tablets at doses of 30 to 90 mg every 12 hours compared with placebo in alleviating moderate to severe pain in patients with chronic low back pain. Patients may be opioid-naïve or opioid-experienced.

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.

The objective of the open label titration period was to find the successful dose of hydrocodone extended release (ER) tablets that produced stable pain relief without unacceptable adverse events (AEs). Stable pain relief was defined as an average pain intensity (API) score over the previous 24 hours of 4 or less and a worst pain intensity (WPI) score of 6 or less on the 11-point numerical rating scale (NRS-11) (0=no pain to 10=worst pain imaginable) for either 4 consecutive days or 4 out of 7 consecutive days, while the same dose of study drug was maintained for up to 7 days. Scores for WPI and API were recorded daily in individual patient electronic diaries. Patients returned to the study center prior to each dose adjustment.

The starting dose of hydrocodone ER tablets depended on whether the subject was opioid-naïve or opioid-experienced. Opioid-naïve participants started at a 15-mg dose of hydrocodone ER tablets every 12 hours. For opioid-experienced participants, the starting dose of hydrocodone ER tablets was to be approximately equivalent to 50% of the dose of opioid analgesic that they were receiving at screening and administered every 12 hours. Investigators switched participants from previous opioid therapy to hydrocodone ER tablets on the basis of predefined dose equivalents.

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). Participants 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.

Participants who participated in the study in compliance with the protocol and complete 12 weeks of double-blind treatment with study drug, were considered to have completed the study and could have been eligible to enroll in a 6-month open-label study (study C32337/3104, NCT01922739).

Eligibility criteria: Inclusion Criteria:

* The patient has had moderate to severe chronic low back pain for at least 3 months duration before screening.
* 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 is willing and able to successfully self-administer the study drug, comply with study restrictions, complete the electronic diary, and return to the study center for scheduled study visits, as specified in the protocol.
* The patient is 18 through 80 years of age at the time of screening.
* Women of childbearing potential (not surgically sterile or 2 years postmenopausal) must use a medically accepted method of contraception, 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. - Acceptable methods of contraception include barrier method with spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method. NOTE: A woman will be considered surgically sterile if she has had a tubal ligation, hysterectomy, bilateral salpingo-oophorectomy or bilateral oophorectomy, or hysterectomy with bilateral salpingo-oophorectomy.
* Other criteria apply.

Exclusion Criteria:

* The patient is taking a total of more than 135 mg/day of oxycodone, or equivalent, during the 14 days before screening.
* The patient's primary painful condition under study is related to any source of chronic pain other than low back pain.
* The patient has radicular (nerve compression) pain or another type of purely neuropathic pain.
* 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.
* The patient has medical or psychiatric disease that, in the opinion of the investigator, would compromise collected data.
* Other criteria apply.

Primary outcomes:
measure: Change From Baseline to Week 12 of the Treatment Period in Weekly Average of Daily Worst Pain Intensity (WPI)
timeFrame: Days -6 to 0 of Treatment Period (baseline), Week 12 of Treatment Period
Secondary outcomes:
measure: Change From Baseline to Week 12 of the Treatment Period in Weekly Average Pain Intensity (API)
timeFrame: Days -6 to 0 of Treatment Period (baseline), Week 12
measure: Kaplan-Meier Estimates for Time to Loss of Efficacy
timeFrame: Day 1 to Week 12 of Treatment Period
measure: Percentage of Participants With a 30% or Greater Increase in Weekly Average Pain Intensity (API) From Baseline to Week 12 Visit, and an Average API Score of 5 or Higher at Week 12
timeFrame: Days -6 to 0 of Treatment Period (baseline), Week 12
measure: Change From Baseline to Final On-Treatment Visit in Roland Morris Disability Questionnaire (RMDQ) Score
timeFrame: Days 7-14 of Titration Period (baseline), Week 12 or end of study visit during the Treatment Period
measure: Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods
timeFrame: Day 1 of Titration Period up to Week 12 of Treatment Period (maximum treatment duration was 127 days)
measure: Participants With Clinically Significant Hearing Changes From Baseline to Final Assessment in Pure Tone Audiometry Test Results
timeFrame: Days 7-14 of Titration Period (baseline), Day 0 of Treatment Period (last day of Titration Period), Week 12 or end of study visit during the Treatment Period
measure: Subjective Opiate Withdrawal Scales (SOWS) Total Scores During the Double-Blind Treatment Period
timeFrame: Weeks 1, 2, 4 and Endpoint of the Treatment Period
measure: Clinical Opiate Withdrawal Scales (COWS) Total Scores During the Double-Blind Treatment Period
timeFrame: Weeks 1, 2, 4 and Endpoint of the Treatment Period
measure: Participants With Potentially Clinically Significant Abnormal Laboratory Values During the Double-Blind Treatment Period
timeFrame: Day 1 up to Week 12 of the Treatment Period
measure: Participants With Potentially Clinically Significant Abnormal Vital Sign Values During the Double-Blind Treatment Period
timeFrame: Day 1 to Week 12 of the Treatment Period
measure: Participants With Potentially Clinically Significant Abnormal Electrocardiogram Findings During the Double-Blind Treatment Period
timeFrame: Final study visit (week 12 or end of treatment visit)
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Teva Investigational Site 10416
state: Alabama
city: Birmingham
country: United States
facility: Teva Investigational Site 10382
state: Alabama
city: Birmingham
country: United States
facility: Teva Investigational Site 10403
state: Alabama
city: Birmingham
country: United States
facility: Teva Investigational Site 10412
state: Alabama
city: Mobile
country: United States
facility: Teva Investigational Site 10426
state: Alabama
city: Montgomery
country: United States
facility: Teva Investigational Site 10436
state: Alabama
city: Phoenix
country: United States
facility: Teva Investigational Site 10363
state: Arizona
city: Phoenix
country: United States
facility: Teva Investigational Site 10366
state: Arizona
city: Tucson
country: United States
facility: Teva Investigational Site 10437
state: Arizona
city: Anaheim
country: United States
facility: Teva Investigational Site 10358
state: California
city: Bell Gardens
country: United States
facility: Teva Investigational Site 10408
state: California
city: Carmichael
country: United States
facility: Teva Investigational Site 10425
state: California
city: Cerritos
country: United States
facility: Teva Investigational Site 10390
state: California
city: El Cajon
country: United States
facility: Teva Investigational Site 10429
state: California
city: Escondido
country: United States
facility: Teva Investigational Site 10423
state: California
city: Garden Grove
country: United States
facility: Teva Investigational Site 10740
state: California
city: Huntington Park
country: United States
facility: Teva Investigational Site 10391
state: California
city: La Jolla
country: United States
facility: Teva Investigational Site 10422
state: California
city: Laguna Hills
country: United States
facility: Teva Investigational Site 10413
state: California
city: Laguna Hills
country: United States
facility: Teva Investigational Site 10442
state: California
city: Los Angeles
country: United States
facility: Teva Investigational Site 10370
state: California
city: Sherman Oaks
country: United States
facility: Teva Investigational Site 10392
state: California
city: Thousand Oaks
country: United States
facility: Teva Investigational Site 10398
state: California
city: Torrance
country: United States
facility: Teva Investigational Site 10428
state: California
city: Walnut Creek
country: United States
facility: Teva Investigational Site 10361
state: California
city: Waterbury
country: United States
facility: Teva Investigational Site 10441
state: Connecticut
city: DeLand
country: United States
facility: Teva Investigational Site 10369
state: Florida
city: Edgewater
country: United States
facility: Teva Investigational Site 10744
state: Florida
city: Fort Lauderdale
country: United States
facility: Teva Investigational Site 10379
state: Florida
city: Jacksonville
country: United States
facility: Teva Investigational Site 10365
state: Florida
city: Leesburg
country: United States
facility: Teva Investigational Site 10445
state: Florida
city: Orlando
country: United States
facility: Teva Investigational Site 10362
state: Florida
city: Ormond Beach
country: United States
facility: Teva Investigational Site 10381
state: Florida
city: Pembroke Pines
country: United States
facility: Teva Investigational Site 12036
state: Florida
city: Plantation
country: United States
facility: Teva Investigational Site 10357
state: Florida
city: Royal Palm Beach
country: United States
facility: Teva Investigational Site 10367
state: Florida
city: Royal Palm Beach
country: United States
facility: Teva Investigational Site 10435
state: Florida
city: Sanford
country: United States
facility: Teva Investigational Site 10742
state: Florida
city: Columbus
country: United States
facility: Teva Investigational Site 10432
state: Georgia
city: Marietta
country: United States
facility: Teva Investigational Site 10383
state: Georgia
city: Marietta
country: United States
facility: Teva Investigational Site 10385
state: Georgia
city: Newnan
country: United States
facility: Teva Investigational Site 10444
state: Georgia
city: Meridian
country: United States
facility: Teva Investigational Site 10431
state: Idaho
city: Meridian
country: United States
facility: Teva Investigational Site 10743
state: Idaho
city: Chicago
country: United States
facility: Teva Investigational Site 10411
state: Illinois
city: Avon
country: United States
facility: Teva Investigational Site 10418
state: Indiana
city: Evansville
country: United States
facility: Teva Investigational Site 10380
state: Indiana
city: Newburgh
country: United States
facility: Teva Investigational Site 10440
state: Indiana
city: Overland Park
country: United States
facility: Teva Investigational Site 10375
state: Kansas
city: New Orleans
country: United States
facility: Teva Investigational Site 10419
state: Louisiana
city: Shreveport
country: United States
facility: Teva Investigational Site 10359
state: Louisiana
city: Fall River
country: United States
facility: Teva Investigational Site 10389
state: Massachusetts
city: Bay City
country: United States
facility: Teva Investigational Site 10388
state: Michigan
city: Biloxi
country: United States
facility: Teva Investigational Site 10397
state: Mississippi
city: Hazelwood
country: United States
facility: Teva Investigational Site 10406
state: Missouri
city: Saint Louis
country: United States
facility: Teva Investigational Site 10401
state: Missouri
city: Omaha
country: United States
facility: Teva Investigational Site 10376
state: Nebraska
city: Omaha
country: United States
facility: Teva Investigational Site 10396
state: Nebraska
city: Henderson
country: United States
facility: Teva Investigational Site 10417
state: Nevada
city: Las Vegas
country: United States
facility: Teva Investigational Site 10399
state: Nevada
city: Berlin
country: United States
facility: Teva Investigational Site 10409
state: New Jersey
city: Buffalo
country: United States
facility: Teva Investigational Site 10439
state: New York
city: New York
country: United States
facility: Teva Investigational Site 10394
state: New York
city: New York
country: United States
facility: Teva Investigational Site 10407
state: New York
city: New York
country: United States
facility: Teva Investigational Site 10410
state: New York
city: Raleigh
country: United States
facility: Teva Investigational Site 10443
state: North Carolina
city: Winston-Salem
country: United States
facility: Teva Investigational Site 10414
state: North Carolina
city: Oklahoma City
country: United States
facility: Teva Investigational Site 10446
state: Oklahoma
city: Altoona
country: United States
facility: Teva Investigational Site 10415
state: Pennsylvania
city: Duncansville
country: United States
facility: Teva Investigational Site 10430
state: Pennsylvania
city: Mechanicsburg
country: United States
facility: Teva Investigational Site 10386
state: Pennsylvania
city: Tipton
country: United States
facility: Teva Investigational Site 10373
state: Pennsylvania
city: North Charleston
country: United States
facility: Teva Investigational Site 10404
state: South Carolina
city: Spartanburg
country: United States
facility: Teva Investigational Site 10741
state: South Carolina
city: Austin
country: United States
facility: Teva Investigational Site 10405
state: Texas
city: Dallas
country: United States
facility: Teva Investigational Site 10364
state: Texas
city: Dallas
country: United States
facility: Teva Investigational Site 10372
state: Texas
city: Dallas
country: United States
facility: Teva Investigational Site 10395
state: Texas
city: Houston
country: United States
facility: Teva Investigational Site 10371
state: Texas
city: Houston
country: United States
facility: Teva Investigational Site 12035
state: Texas
city: Lake Jackson
country: United States
facility: Teva Investigational Site 10377
state: Texas
city: Plano
country: United States
facility: Teva Investigational Site 10374
state: Texas
city: San Antonio
country: United States
facility: Teva Investigational Site 10378
state: Texas
city: Salt Lake City
country: United States
facility: Teva Investigational Site 10402
state: Utah
city: Roanoke
country: United States
facility: Teva Investigational Site 10438
state: Virginia
city: Bellevue
country: United States
facility: Teva Investigational Site 10420
state: Washington
city: Everett
country: United States
facility: Teva Investigational Site 10433
state: Washington
Study officials:
affiliation: Teva GCO
name: Clinical Project Leader
role: STUDY_DIRECTOR
References: