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

NCT ID: NCT01789970

Last Updated: 2017-06-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 625 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2014-02-28

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).

Conditions

Low Back Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Hydrocodone ER

Intervention Type: 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.

Placebo

Intervention Type: 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.

Hydrocodone ER

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.

Group Type: EXPERIMENTAL

Hydrocodone ER

Intervention Type: 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.

Interventions

Hydrocodone ER

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

CEP-33237; Hydrocodone bitartrate extended-release tablets

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Teva Branded Pharmaceutical Products R&D, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Project Leader

Role: STUDY_DIRECTOR

Teva GCO

Locations

Teva Investigational Site 10416

Anniston, Alabama, United States

Teva Investigational Site 10382

Birmingham, Alabama, United States

Teva Investigational Site 10403

Birmingham, Alabama, United States

Teva Investigational Site 10412

Birmingham, Alabama, United States

Teva Investigational Site 10426

Mobile, Alabama, United States

Teva Investigational Site 10436

Montgomery, Alabama, United States

Teva Investigational Site 10363

Phoenix, Arizona, United States

Teva Investigational Site 10366

Phoenix, Arizona, United States

Teva Investigational Site 10437

Tucson, Arizona, United States

Teva Investigational Site 10358

Anaheim, California, United States

Teva Investigational Site 10408

Bell Gardens, California, United States

Teva Investigational Site 10425

Carmichael, California, United States

Teva Investigational Site 10390

Cerritos, California, United States

Teva Investigational Site 10429

El Cajon, California, United States

Teva Investigational Site 10423

Escondido, California, United States

Teva Investigational Site 10740

Garden Grove, California, United States

Teva Investigational Site 10391

Huntington Park, California, United States

Teva Investigational Site 10422

La Jolla, California, United States

Teva Investigational Site 10413

Laguna Hills, California, United States

Teva Investigational Site 10442

Laguna Hills, California, United States

Teva Investigational Site 10370

Los Angeles, California, United States

Teva Investigational Site 10392

Sherman Oaks, California, United States

Teva Investigational Site 10398

Thousand Oaks, California, United States

Teva Investigational Site 10428

Torrance, California, United States

Teva Investigational Site 10361

Walnut Creek, California, United States

Teva Investigational Site 10441

Waterbury, Connecticut, United States

Teva Investigational Site 10369

DeLand, Florida, United States

Teva Investigational Site 10744

Edgewater, Florida, United States

Teva Investigational Site 10379

Fort Lauderdale, Florida, United States

Teva Investigational Site 10365

Jacksonville, Florida, United States

Teva Investigational Site 10445

Leesburg, Florida, United States

Teva Investigational Site 10362

Orlando, Florida, United States

Teva Investigational Site 10381

Ormond Beach, Florida, United States

Teva Investigational Site 12036

Pembroke Pines, Florida, United States

Teva Investigational Site 10357

Plantation, Florida, United States

Teva Investigational Site 10367

Royal Palm Beach, Florida, United States

Teva Investigational Site 10435

Royal Palm Beach, Florida, United States

Teva Investigational Site 10742

Sanford, Florida, United States

Teva Investigational Site 10432

Columbus, Georgia, United States

Teva Investigational Site 10383

Marietta, Georgia, United States

Teva Investigational Site 10385

Marietta, Georgia, United States

Teva Investigational Site 10444

Newnan, Georgia, United States

Teva Investigational Site 10431

Meridian, Idaho, United States

Teva Investigational Site 10743

Meridian, Idaho, United States

Teva Investigational Site 10411

Chicago, Illinois, United States

Teva Investigational Site 10418

Avon, Indiana, United States

Teva Investigational Site 10380

Evansville, Indiana, United States

Teva Investigational Site 10440

Newburgh, Indiana, United States

Teva Investigational Site 10375

Overland Park, Kansas, United States

Teva Investigational Site 10419

New Orleans, Louisiana, United States

Teva Investigational Site 10359

Shreveport, Louisiana, United States

Teva Investigational Site 10389

Fall River, Massachusetts, United States

Teva Investigational Site 10388

Bay City, Michigan, United States

Teva Investigational Site 10397

Biloxi, Mississippi, United States

Teva Investigational Site 10406

Hazelwood, Missouri, United States

Teva Investigational Site 10401

St Louis, Missouri, United States

Teva Investigational Site 10376

Omaha, Nebraska, United States

Teva Investigational Site 10396

Omaha, Nebraska, United States

Teva Investigational Site 10417

Henderson, Nevada, United States

Teva Investigational Site 10399

Las Vegas, Nevada, United States

Teva Investigational Site 10409

Berlin, New Jersey, United States

Teva Investigational Site 10439

Buffalo, New York, United States

Teva Investigational Site 10394

New York, New York, United States

Teva Investigational Site 10407

New York, New York, United States

Teva Investigational Site 10410

New York, New York, United States

Teva Investigational Site 10443

Raleigh, North Carolina, United States

Teva Investigational Site 10414

Winston-Salem, North Carolina, United States

Teva Investigational Site 10446

Oklahoma City, Oklahoma, United States

Teva Investigational Site 10415

Altoona, Pennsylvania, United States

Teva Investigational Site 10430

Duncansville, Pennsylvania, United States

Teva Investigational Site 10386

Mechanicsburg, Pennsylvania, United States

Teva Investigational Site 10373

Tipton, Pennsylvania, United States

Teva Investigational Site 10404

North Charleston, South Carolina, United States

Teva Investigational Site 10741

Spartanburg, South Carolina, United States

Teva Investigational Site 10405

Austin, Texas, United States

Teva Investigational Site 10364

Dallas, Texas, United States

Teva Investigational Site 10372

Dallas, Texas, United States

Teva Investigational Site 10395

Dallas, Texas, United States

Teva Investigational Site 10371

Houston, Texas, United States

Teva Investigational Site 12035

Houston, Texas, United States

Teva Investigational Site 10377

Lake Jackson, Texas, United States

Teva Investigational Site 10374

Plano, Texas, United States

Teva Investigational Site 10378

San Antonio, Texas, United States

Teva Investigational Site 10402

Salt Lake City, Utah, United States

Teva Investigational Site 10438

Roanoke, Virginia, United States

Teva Investigational Site 10420

Bellevue, Washington, United States

Teva Investigational Site 10433

Everett, Washington, United States

Countries

United States

Other Identifiers

C33237/3103

Identifier Type: -

Identifier Source: org_study_id