Clinical trial NCT01789970
Conditions: Low Back Pain
Keywords: chronic low back pain hydrocodone bitartrate opioids
Sponsor: Teva Branded Pharmaceutical Products R&D, Inc.
Start date: 2013-03-01; Completion date: 2014-02-01
Enrollment: 625 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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).

Arms: arm 1: 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. arm 2: 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.
Interventions: intervention 1: Hydrocodone ER intervention 2: Placebo
Intervention descriptions: intervention 1: 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 2: 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.

Protocol documents: