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

These 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).No 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).Results 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.ClinicalTrials.gov identifier: NCT00412100 and NCT00412152Opioids are established treatment for moderate/severe chronic malignant pain, as recommended by the World Health Organization (WHO) [1]; furthermore, they are the mainstay of treatment for chronic non-malignant pain [2]. Oxycodone is a semi-synthetic, opioid that is effective in alleviating malignant pain [3,4], postoperative pain, osteoarthritis [5] and neuropathic non-malignant pain [6-8].Opioids exert their analgesic effects mainly by binding to receptors within the central nervous system; however, opioid receptors also reside within the gastrointestinal (GI) tract [9]. Binding of opioids to these receptors commonly leads to GI adverse events (AEs), including straining, incomplete evacuation, bloating, abdominal dis