J Opioid Manag 2015 Nov-Dec;11(6):507-18
Teva Pharmaceuticals, Frazer, Pennsylvania.
Objective: To evaluate efficacy and safety of hydrocodone bitartrate extended release (ER) tablets developed with CIMA(®) Abuse-Deterrence Technology (ADT) versus placebo in alleviating moderate-to-severe pain in patients with chronic low back pain.
Design: Phase 3, randomized, double-blind study consisting of a screening period (7-14 days), open-label titration period (≤ 6 weeks), and double-blind treatment period (≤ 12 weeks).
Setting: Seventy-eight US centers.
Main Outcome Measures: Changes from baseline at week 12 in weekly average of daily worst pain intensity (WPI; primary efficacy measure), weekly average pain intensity (API; secondary efficacy measure), adverse events (AEs), and study drug loss and diversion.
Results: Patients (N = 625) who entered open-label dose titration and identified the analgesic hydrocodone ER dose (30-90 mg every 12 h) providing optimal pain relief with minimal AEs were randomized to hydrocodone ER (n = 191) or placebo (n = 180) for double-blind treatment at the identified dose; 297 patients completed the study. Least squares means [SE] changes from baseline were significantly greater (worsening pain; 11-point scale) with placebo than hydrocodone ER in weekly average of daily WPI (0.74 [0.15] vs 0.11 [0.14]; p < 0.001) and weekly API (0.55 [0.14] vs -0.03 [0.12]; p < 0.001). The most common AEs with hydrocodone ER were constipation (14 percent) and nausea (10 percent). Study drug loss (≤ 4 percent) and diversion (≤ 2 percent) rates were low.
Conclusions: Hydrocodone ER formulated with ADT was significantly more effective than placebo in alleviating chronic low back pain and demonstrated a safety profile consistent with that of opioids, with a low occurrence of study drug loss and diversion.