Clinical trial NCT01922739: Open-Label, Extension Study to Evaluate the Safety of Hydrocodone Bitartrate Extended-Release Tablets
Official title: A 6-Month, Open-Label, Extension Study to Evaluate the 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 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: low back pain
hydrocodone bitartrate
opioids
Lead sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Sponsor class: INDUSTRY
First posted: 2013-08-14
Enrollment: 182
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: This is a 6-month, nonrandomized, open-label extension study to assess the long-term safety of hydrocodone bitartrate extended-release (ER) tablets in patients with moderate to severe chronic low back pain who require continuous opioid treatment for an extended period of time.

To be eligible for Study 3104, patients were required to have completed the entire double blind treatment period on study drug (either placebo or hydrocodone bitartrate ER tablets) through week 12 of Study 3103 (NCT01789970) and to have met the entry criteria for Study 3104.

Detailed description: Eligible patients from Study 3103 (NCT01789970) were enrolled for participation in this extension study. For these patients, the final study visit in Study 3103 was visit 1 for this study (also referred to as the titration or adjustment baseline visit, depending on whether the patient was enrolled under the original or amended protocol, respectively). The original protocol was amended after 26 patients had been enrolled in the study. Those who were enrolled under the original protocol participated in a double-blind titration period of up to approximately 4 weeks followed by an open-label treatment period of 22 weeks. Those patients who were enrolled under the amended protocol participated in an open-label adjustment period of up to approximately 3 weeks followed by an open-label treatment period of 22 weeks.

Eligibility criteria: Inclusion Criteria:

1. Patients must have participated in and completed the entire double-blind treatment period on study drug through the final study visit (week 12) of study 3103.

   NOTE: Patients who had a final on-treatment visit (i.e. prior to week 12) are not permitted to participate in study 3104.
2. The patient is able to speak English and is willing to provide written informed consent for study 3104, including re-signing a written opioid agreement, to participate in this study.
3. 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.
4. The patient must be willing and able to successfully self-administer the study drug, comply with study restrictions, and return to the study center for scheduled study visits, as specified in the protocol.
5. The patient must not participate in any other study involving an investigational agent (excluding those who participated in study 3103) while enrolled in the present study.

Exclusion Criteria:

1. The patient's current source of pain is different from the low back pain the patient was experiencing at entry into study 3103. NOTE: Any additional source of pain for a patient must be discussed with the medical monitor.
2. The patient has current evidence of alcohol or other substance abuse with the exception of nicotine or caffeine.
3. The patient has developed, during study 3103, a medical or psychiatric disease (including suicidality) that, in the opinion of the investigator, would compromise collected data.
4. The patient is expected to have surgery during the study.
5. The patient is pregnant or lactating.
6. The patient has developed an active malignancy (excluding basal cell carcinoma) during study 3103.
7. The patient has known human immunodeficiency virus (HIV).
8. 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.
9. The patient has developed cardiopulmonary disease that would, in the opinion of the investigator, significantly increase the risk of treatment with opioids.
10. The patient is receiving a monoamine oxidase inhibitor (MAOI).

    * Other exclusion criteria apply.

Primary outcomes:
measure: Participants With Adverse Events
timeFrame: Day 1 of the Titration/Adjustment Period to Week 22 of the Treatment Period (total of 25-26 weeks)
measure: Participants With Potentially Clinically Significant Abnormal Laboratory Values
timeFrame: End of trial visit (up to week 22 of Open-label Treatment Period which is up to week 26 including the titration/adjustment period)
measure: Participants With Potentially Clinically Significant Abnormal Vital Signs Values
timeFrame: Day 1 of the Titration/Adjustment Period to Week 22 of the Treatment Period (total of 25-26 weeks)
measure: Participants With Shifts From Normal to Abnormal in Physical Examination Findings
timeFrame: End of trial visit (up to week 22 of Open-label Treatment Period which is up to week 26 including the titration/adjustment period)
measure: Shifts From Baseline to Endpoint (Treatment Period) in Electrocardiogram (ECG) Findings
timeFrame: Baseline (final visit for study 3103), End of trial visit (up to week 22 of Open-label Treatment Period which is up to week 26 including the titration/adjustment period)
measure: Participants With Clinically Significant (CS) Hearing Changes From Baseline to the Final Visit in Pure Tone Audiometry Test Results
timeFrame: Baseline was within two weeks of the final study visit in study 3103; during study exam was within two weeks of the end of trial visit for study 3104 (up to study week 26)
Secondary outcomes:
measure: Change From Baseline to Weeks 2, 6, 10, 14, 18, 22 and Endpoint of the Treatment Period in Daily Worst Pain Intensity (WPI) Scores During the Previous 24 Hours for Each Visit
timeFrame: Baseline (Day 0 of Treatment Period), Weeks 2, 6, 10, 14, 18, 22 and Endpoint during the Open-Label Treatment Period
measure: Change From Baseline to Weeks 2, 6, 10, 14, 18, 22 and Endpoint of the Treatment Period in Daily Average Pain Intensity (API) Scores During the Previous 24 Hours for Each Visit
timeFrame: Baseline (Day 0 of Treatment Period), Weeks 2, 6, 10, 14, 18, 22 and Endpoint during the Open-Label Treatment Period
measure: Percentage of Participants Withdrawn From the Study For Lack of Efficacy
timeFrame: Day 1 of the Titration/Adjustment Period to Week 22 of the Treatment Period (total of 25-26 weeks)
Other outcomes:
Locations:
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: Huntington Park
country: United States
facility: Teva Investigational Site 10391
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: DeLand
country: United States
facility: Teva Investigational Site 10369
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: Plantation
country: United States
facility: Teva Investigational Site 10357
state: Florida
city: Royal Palm Beach
country: United States
facility: Teva Investigational Site 10435
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: Newburgh
country: United States
facility: Teva Investigational Site 10440
state: Indiana
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: 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 10410
state: New York
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: 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: 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: Houston
country: United States
facility: Teva Investigational Site 10371
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: 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 Branded Pharmaceutical Products R&D, Inc.
name: Teva Medical Expert, MD
role: STUDY_DIRECTOR
References: