Open-Label, Extension Study to Evaluate the Safety of Hydrocodone Bitartrate Extended-Release Tablets

NCT01922739 | Completed Phase 3 Results

• 1 other identifier: C33237/3104
• Study Type: interventional
• Target: 182
• Locations: 1 country
• Sites: 61

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.

Conditions

Low Back Pain

Keywords

low back pain; hydrocodone bitartrate; opioids

Outcome Measures

Primary Outcomes (6)

• Participants With Adverse Events

  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. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an inability to carry out usual activities. 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 the Titration/Adjustment Period to Week 22 of the Treatment Period (total of 25-26 weeks)

• Participants With Potentially Clinically Significant Abnormal Laboratory Values

  Data represents participants with potentially clinically significant abnormal serum chemistry, hematology and urinalysis values. Significance criteria: * Blood urea nitrogen: \>=10.71 mmol/L * Creatinine: \>=177 μmol/L * Uric acid: M\>=625, F\>=506 μmol/L * Aspartate aminotransferase (AST): \>=3\* upper limit of normal (ULN) * Alkaline phosphatase: \>=3\* upper limit of normal (ULN) * Gamma-glutamyl transpeptidase (GGT): \>=3\* upper limit of normal (ULN) * Serum white blood cells: \>=20 \* 10\^9/L * Hemoglobin: M\<=115, F\<=95 g/dL * Hematocrit: M\<0.37, F\<0.32 L/L * Eosinophils: \>=10.0 % * Platelets: \<=75 \* 10\^9/L * Absolute neutrophils: \<=1.0 \* 10\^9/L * Urinalysis: Glucose, Ketones, and Total Protein: \>=2 unit increase from baseline

  End of trial visit (up to week 22 of Open-label Treatment Period which is up to week 26 including the titration/adjustment period)

• Participants With Potentially Clinically Significant Abnormal Vital Signs Values

  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 the Titration/Adjustment Period to Week 22 of the Treatment Period (total of 25-26 weeks)

• Participants With Shifts From Normal to Abnormal in Physical Examination Findings

  The endpoint visit or early termination visit was an abbreviated exam. Endpoint refers to the last observation carried forward.

  End of trial visit (up to week 22 of Open-label Treatment Period which is up to week 26 including the titration/adjustment period)

• Shifts From Baseline to Endpoint (Treatment Period) in Electrocardiogram (ECG) Findings

  A 12-lead ECG was conducted at the final visit for study 3103 which is used as baseline for this study, and at week 22 of the treatment period \[or early termination\]). A qualified physician at the study center was responsible for providing interpretation of the ECG. Endpoint refers to the last observation carried forward.

  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)

• Participants With Clinically Significant (CS) Hearing Changes From Baseline to the Final Visit in Pure Tone Audiometry Test Results

  Pure tone audiometry was performed by trained personnel. Hearing loss was classified in degrees of hearing from normal to profound. This classification was determined by the hearing threshold (or the softest sound detected at a specific frequency). The exact ranges that classified hearing loss depended on the exact technique used during testing and on the patient's age. These values were provided by each audiology laboratory that performed the test. For serial audiograms, the criteria for a clinically significant hearing change were based on guidance from the American Speech Language Hearing Association (ASHA 1994, cited in \[Konrad-Martin et al 2005\]). 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 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 (3)

• 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

  Baseline (Day 0 of Treatment Period), Weeks 2, 6, 10, 14, 18, 22 and Endpoint during the Open-Label Treatment Period

• 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

  Baseline (Day 0 of Treatment Period), Weeks 2, 6, 10, 14, 18, 22 and Endpoint during the Open-Label Treatment Period

• Percentage of Participants Withdrawn From the Study For Lack of Efficacy

  Day 1 of the Titration/Adjustment Period to Week 22 of the Treatment Period (total of 25-26 weeks)

Study Arms (1)

Hydrocodone ER

EXPERIMENTAL

Participants were administered hydrocodone ER tablets orally at dosages of 15, 30, 45, 60, or 90 mg every 12 hours at the dosage deemed successful for managing their pain. If enrolled under the original protocol, there was a double-blind titration period of four weeks to adjust the dose taken in study 3103 (NCT01789970). If enrolled under the amended protocol, there was an open-label adjustment period of three weeks to adjust the dose taken in study 3103 (NCT01789970). Both versions of protocol 3104 followed the titration/adjustment period with a open-label treatment period of 22 weeks.

Drug: Hydrocodone ER; Drug: Placebo

Interventions

Hydrocodone ER DRUG

Participants were instructed to take hydrocodone ER tablets orally with a glass of water on an empty stomach at least 1 hour before or 2 hours after eating.

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

Hydrocodone ER

Placebo DRUG

During the double-blind titration period used in the original protocol, placebo tablets matching each dose of hydrocodone bitartrate ER tablets (active drug) were used to maintain the blind but not for purposes of comparison.

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:

• 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.
• 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.
• 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.
• 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.
• 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.

You may not qualify if:

• 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.
• The patient has current evidence of alcohol or other substance abuse with the exception of nicotine or caffeine.
• 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.
• The patient is expected to have surgery during the study.
• The patient is pregnant or lactating.
• The patient has developed an active malignancy (excluding basal cell carcinoma) during study 3103.
• The patient has known 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 developed cardiopulmonary disease that would, in the opinion of the investigator, significantly increase the risk of treatment with opioids.
• The patient is receiving a monoamine oxidase inhibitor (MAOI).

Sponsors & Collaborators

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

Study Sites (61)

Teva Investigational Site 10412

Birmingham, Alabama, United States

Location

Teva Investigational Site 10426

Mobile, Alabama, United States

Location

Teva Investigational Site 10436

Montgomery, Alabama, United States

Location

Teva Investigational Site 10363

Phoenix, Arizona, United States

Location

Teva Investigational Site 10366

Phoenix, Arizona, United States

Location

Teva Investigational Site 10437

Tucson, Arizona, United States

Location

Teva Investigational Site 10358

Anaheim, California, United States

Location

Teva Investigational Site 10408

Bell Gardens, California, United States

Location

Teva Investigational Site 10425

Carmichael, California, United States

Location

Teva Investigational Site 10390

Cerritos, California, United States

Location

Teva Investigational Site 10429

El Cajon, California, United States

Location

Teva Investigational Site 10423

Escondido, California, United States

Location

Teva Investigational Site 10391

Huntington Park, California, United States

Location

Teva Investigational Site 10370

Los Angeles, California, United States

Location

Teva Investigational Site 10392

Sherman Oaks, California, United States

Location

Teva Investigational Site 10398

Thousand Oaks, California, United States

Location

Teva Investigational Site 10428

Torrance, California, United States

Location

Teva Investigational Site 10361

Walnut Creek, California, United States

Location

Teva Investigational Site 10369

DeLand, Florida, United States

Location

Teva Investigational Site 10379

Fort Lauderdale, Florida, United States

Location

Teva Investigational Site 10365

Jacksonville, Florida, United States

Location

Teva Investigational Site 10445

Leesburg, Florida, United States

Location

Teva Investigational Site 10362

Orlando, Florida, United States

Location

Teva Investigational Site 10381

Ormond Beach, Florida, United States

Location

Teva Investigational Site 10357

Plantation, Florida, United States

Location

Teva Investigational Site 10435

Royal Palm Beach, Florida, United States

Location

Teva Investigational Site 10432

Columbus, Georgia, United States

Location

Teva Investigational Site 10383

Marietta, Georgia, United States

Location

Teva Investigational Site 10385

Marietta, Georgia, United States

Location

Teva Investigational Site 10444

Newnan, Georgia, United States

Location

Teva Investigational Site 10431

Meridian, Idaho, United States

Location

Teva Investigational Site 10743

Meridian, Idaho, United States

Location

Teva Investigational Site 10411

Chicago, Illinois, United States

Location

Teva Investigational Site 10440

Newburgh, Indiana, United States

Location

Teva Investigational Site 10419

New Orleans, Louisiana, United States

Location

Teva Investigational Site 10359

Shreveport, Louisiana, United States

Location

Teva Investigational Site 10389

Fall River, Massachusetts, United States

Location

Teva Investigational Site 10388

Bay City, Michigan, United States

Location

Teva Investigational Site 10397

Biloxi, Mississippi, United States

Location

Teva Investigational Site 10406

Hazelwood, Missouri, United States

Location

Teva Investigational Site 10401

St Louis, Missouri, United States

Location

Teva Investigational Site 10376

Omaha, Nebraska, United States

Location

Teva Investigational Site 10399

Las Vegas, Nevada, United States

Location

Teva Investigational Site 10409

Berlin, New Jersey, United States

Location

Teva Investigational Site 10439

Buffalo, New York, United States

Location

Teva Investigational Site 10410

New York, New York, United States

Location

Teva Investigational Site 10414

Winston-Salem, North Carolina, United States

Location

Teva Investigational Site 10446

Oklahoma City, Oklahoma, United States

Location

Teva Investigational Site 10430

Duncansville, Pennsylvania, United States

Location

Teva Investigational Site 10386

Mechanicsburg, Pennsylvania, United States

Location

Teva Investigational Site 10373

Tipton, Pennsylvania, United States

Location

Teva Investigational Site 10405

Austin, Texas, United States

Location

Teva Investigational Site 10364

Dallas, Texas, United States

Location

Teva Investigational Site 10372

Dallas, Texas, United States

Location

Teva Investigational Site 10371

Houston, Texas, United States

Location

Teva Investigational Site 10377

Lake Jackson, Texas, United States

Location

Teva Investigational Site 10374

Plano, Texas, United States

Location

Teva Investigational Site 10378

San Antonio, Texas, United States

Location

Teva Investigational Site 10402

Salt Lake City, Utah, United States

Location

Teva Investigational Site 10420

Bellevue, Washington, United States

Location

Teva Investigational Site 10433

Everett, Washington, United States

Location

MeSH Terms

Conditions

Low Back Pain

Condition Hierarchy (Ancestors)

Back Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products, R&D Inc.

ustevatrials@tevapharm.com

215-591-3000

Study Officials

• Teva Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  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: August 12, 2013
• First Posted: August 14, 2013
• Study Start: July 1, 2013
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: November 9, 2021
• Results First Posted: June 2, 2017

Record last verified: 2021-11

Locations

US (61)