Efficacy and safety of combined prolonged-release oxycodone and naloxone in the management of moderate/severe chronic non-malignant pain: results of a prospectively designed pooled analysis of two randomised, double-blind clinical trials.

Oliver Löwenstein,Karen Reimer,Björn Bosse,Petra Leyendecker,Michael Hopp,Eberhard A Lux,Mark Blagden,Karen H Simpson

doi:10.1186/1472-6904-10-12

Abstract

BackgroundTwo randomised 12-week, double-blind, parallel-group, multicenter studies comparing oxycodone PR/naloxone PR and oxycodone PR alone on symptoms of opioid-induced bowel dysfunction in patients with moderate/severe non-malignant pain have been conducted.MethodsThese studies were prospectively designed to be pooled and the primary outcome measure of the pooled data analysis was to demonstrate non-inferiority in 12-week analgesic efficacy of oxycodone PR/naloxone PR versus oxycodone PR alone. Patients with opioid-induced constipation were switched to oxycodone PR and then randomised to fixed doses of oxycodone PR/naloxone PR (n = 292) or oxycodone PR (n = 295) for 12 weeks (20-80 mg/day).ResultsNo statistically significant differences in analgesic efficacy were observed for the two treatments (p = 0.3197; non-inferiority p < 0.0001; 95% CI -0.07, 0.23) and there was no statistically significant difference in frequency of analgesic rescue medication use. Improvements in Bowel Function Index score were observed for oxycodone PR/naloxone PR by Week 1 and at every subsequent time point (-15.1; p < 0.0001; 95% CI -17.3, -13.0). AE incidence was similar for both groups (61.0% and 57.3% of patients with oxycodone PR/naloxone PR and oxycodone PR alone, respectively).ConclusionsResults of this pooled analysis confirm that oxycodone PR/naloxone PR provides effective analgesia and suggest that oxycodone PR/naloxone PR improves bowel function without compromising analgesic efficacy.Trial registration numbersClinicalTrials.gov identifier: NCT00412100 and NCT00412152

Highlights

Two randomised 12-week, double-blind, parallel-group, multicenter studies comparing oxycodone PR/naloxone PR and oxycodone PR alone on symptoms of opioid-induced bowel dysfunction in patients with moderate/severe non-malignant pain have been conducted
Binding of opioids to these receptors commonly leads to GI adverse events (AEs), including straining, incomplete evacuation, bloating, abdominal distension and gastric reflux that are collectively known as opioid-induced bowel dysfunction[10]
The primary focus of the pooled analysis was to examine the analgesic efficacy of oxycodone PR/naloxone PR compared with oxycodone PR alone during 12 weeks of treatment

Summary

Introduction

Two randomised 12-week, double-blind, parallel-group, multicenter studies comparing oxycodone PR/naloxone PR and oxycodone PR alone on symptoms of opioid-induced bowel dysfunction in patients with moderate/severe non-malignant pain have been conducted. Opioids are established treatment for moderate/severe chronic malignant pain, as recommended by the World Health Organization (WHO) [1]; they are the mainstay of treatment for chronic non-malignant Opioids exert their analgesic effects mainly by binding to receptors within the central nervous system; opioid receptors reside within the gastrointestinal (GI) tract [9]. Only 46% of patients taking medication for OIC experienced improvement for over 50% of the time compared with 80% of non-opioid users taking similar medication for constipation [10]. This may be because laxatives do not counteract the underlying opioid receptor-mediated mechanism of OIC. Prevention of OIC, and bowel dysfunction, is a more effective strategy than treating it once it occurs [9]

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Results

Discussion

Conclusion