Efficacy and safety of a hydrocodone extended-release tablet formulated with abuse-deterrence technology in patients with moderate-to-severe chronic low back pain

Martin E. Hale, MD; Thomas R. Zimmerman, MD; Eli Eyal, MSc; Richard Malamut, MD

doi:10.5055/jom.2015.0304

Authors

Martin E. Hale, MD
Thomas R. Zimmerman, MD
Eli Eyal, MSc
Richard Malamut, MD

DOI:

https://doi.org/10.5055/jom.2015.0304

Keywords:

hydrocodone, prescription opioids, abuse-deterrent, pain medication

Abstract

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.

Author Biographies

Martin E. Hale, MD

Medical Director, Gold Coast Research, LLC, Plantation, Florida

Thomas R. Zimmerman, MD

Consultant to Teva Pharmaceuticals, Frazer, Pennsylvania

Eli Eyal, MSc

Teva Pharmaceuticals, Netanya, Israel

Richard Malamut, MD

Teva Pharmaceuticals, Frazer, Pennsylvania

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