Efficacy and Safety of Hydrocodone Bitartrate Extended-Release Tablets for Moderate to Severe Chronic Low Back Pain

NCT01789970 | Completed Phase 3 Results

• 1 other identifier: C33237/3103
• Study Type: interventional
• Target: 625
• Locations: 1 country
• Sites: 87

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.

Conditions

Low Back Pain

Keywords

chronic low back pain; hydrocodone bitartrate; opioids

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 12 of the Treatment Period in Weekly Average of Daily Worst Pain Intensity (WPI)

  The WPI was recorded daily by participants in an electronic diary using an 11-point numerical rating scale (NRS-11), a Likert-type scale in which 0=no pain and 10=the worst pain imaginable. Participants selected the number that best described their worst pain intensity over the last 24 hours. Weekly WPI scores averaged daily scores collected over the previous 7 days for each analysis visit. Negative change from baseline scores indicate improvement in pain control. The analysis included WPI data observed before discontinuation of study drug and was based on the multiple imputations (MI) method to handle missing scores at week 12. Consistent with the recommendations of the National Academy of Sciences (NAS) report (Panel on Handling Missing Data in Clinical Trials 2010), the MI method includes an assumption of missing at random (MAR) and takes into account a potential bias toward the active-drug treatment group for patients who discontinued study drug because of adverse events.

  Days -6 to 0 of Treatment Period (baseline), Week 12 of Treatment Period

Secondary Outcomes (11)

• Change From Baseline to Week 12 of the Treatment Period in Weekly Average Pain Intensity (API)

  Days -6 to 0 of Treatment Period (baseline), Week 12

• Kaplan-Meier Estimates for Time to Loss of Efficacy

  Day 1 to Week 12 of Treatment Period

• 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

  Days -6 to 0 of Treatment Period (baseline), Week 12

• Change From Baseline to Final On-Treatment Visit in Roland Morris Disability Questionnaire (RMDQ) Score

  Days 7-14 of Titration Period (baseline), Week 12 or end of study visit during the Treatment Period

• Participants With Adverse Events During Open-Label Titration and Double-Blind Treatment Periods

  Day 1 of Titration Period up to Week 12 of Treatment Period (maximum treatment duration was 127 days)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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 during the titration period. During the treatment period, participants were administered placebo tablets twice a day that matched the dosage deemed successful for managing their pain during the titration period. A step-wise, double-blind schedule to tamper off active drug was implemented during the first 2 weeks of the 12-week, double-blind, placebo-controlled treatment period to reduce the risk of withdrawal effects in participants randomly assigned to placebo.

Drug: Hydrocodone ER; Drug: Placebo

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 during the titration period. During the 12-week, double-blind, placebo-controlled treatment period, participants randomly assigned to hydrocodone ER were administered tablets twice a day at the dosage deemed successful for managing their pain during the titration period.

Drug: Hydrocodone ER

Interventions

Hydrocodone ER DRUG

During the open-label, titration period, all participants were administered hydrocodone ER tablets at dosages of 15, 30, 45, 60, or 90 mg every 12 hours to identify a dosage deemed successful for managing their pain. Hydrocodone ER was taken by participants randomized to the hydrocodone ER treatment arm during the double-blind treatment period at the dose level identified during the titration period. Participants were instructed to take tablets 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

Placebo DRUG

Placebo matching the active drug dose identified during the titration period was taken by participants randomized to the placebo treatment arm during the double-blind treatment period. Participants were instructed to take intervention with a glass of water on an empty stomach at least 1 hour before or 2 hours after eating.

Placebo

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 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (87)

Teva Investigational Site 10416

Anniston, Alabama, United States

Location

Teva Investigational Site 10382

Birmingham, Alabama, United States

Location

Teva Investigational Site 10403

Birmingham, Alabama, United States

Location

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 10740

Garden Grove, California, United States

Location

Teva Investigational Site 10391

Huntington Park, California, United States

Location

Teva Investigational Site 10422

La Jolla, California, United States

Location

Teva Investigational Site 10413

Laguna Hills, California, United States

Location

Teva Investigational Site 10442

Laguna Hills, 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 10441

Waterbury, Connecticut, United States

Location

Teva Investigational Site 10369

DeLand, Florida, United States

Location

Teva Investigational Site 10744

Edgewater, 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 12036

Pembroke Pines, Florida, United States

Location

Teva Investigational Site 10357

Plantation, Florida, United States

Location

Teva Investigational Site 10367

Royal Palm Beach, Florida, United States

Location

Teva Investigational Site 10435

Royal Palm Beach, Florida, United States

Location

Teva Investigational Site 10742

Sanford, 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 10418

Avon, Indiana, United States

Location

Teva Investigational Site 10380

Evansville, Indiana, United States

Location

Teva Investigational Site 10440

Newburgh, Indiana, United States

Location

Teva Investigational Site 10375

Overland Park, Kansas, 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 10396

Omaha, Nebraska, United States

Location

Teva Investigational Site 10417

Henderson, Nevada, 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 10394

New York, New York, United States

Location

Teva Investigational Site 10407

New York, New York, United States

Location

Teva Investigational Site 10410

New York, New York, United States

Location

Teva Investigational Site 10443

Raleigh, North Carolina, 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 10415

Altoona, Pennsylvania, 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 10404

North Charleston, South Carolina, United States

Location

Teva Investigational Site 10741

Spartanburg, South Carolina, 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 10395

Dallas, Texas, United States

Location

Teva Investigational Site 10371

Houston, Texas, United States

Location

Teva Investigational Site 12035

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 10438

Roanoke, Virginia, 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

• Clinical Project Leader

  Teva GCO

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2013
• First Posted: February 12, 2013
• Study Start: March 1, 2013
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: June 5, 2017
• Results First Posted: April 5, 2017

Record last verified: 2017-06

Locations

US (87)