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

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

Combined oral prolonged-release oxycodone and naloxone in chronic pain management

“…This pooled analysis demonstrated that during a 12-week period, PR OXN provided analgesia that was as effective as PR OX alone, as indicated by the noninferiority of PR OXN versus PR OX in mean pain intensity, and a low and comparable use of supplemental analgesic medication in both treatment arms. Of interest, patients receiving PR OXN demonstrated clinically significant improvements in OIC, and there was also a significantly reduced use of laxatives in the first 4 weeks of the study in patients who received PR OXN compared with those who received PR OX alone [18].…”

The Bowel Function Index for Evaluating Constipation in Pain Patients: Definition of a Reference Range for a Non-Constipated Population of Pain Patients

“…These data were taken from a meta-analysis of the safety and efficacy of oxycodone PR/naloxone PR tablets versus oxycodone PR tablets. 21 This comprised two very similar controlled, randomized, double-blind studies undertaken in 119 and 99 centres, respectively, involving 587 patients with moderate-to-severe chronic pain. 16,22 The BFI values at randomization were used to determine symptoms of constipation; subjects who reported fewer than three complete spontaneous bowel movements per week, without the need to strain, fulfilled the opioid-related constipation criterion required by the protocol of the present study and were included in the OIC population.…”

Effectiveness and tolerability of low-dose oral oxycodone/naloxone added to anticonvulsant therapy for noncancer neuropathic pain: an observational analysis

“…Some experimental and clinical findings suggest that the positive reinforcing effects that lead to opioid abuse are diminished or even absent in individuals with severe chronic pain, making opioid addiction less likely 51,52 . Of note, withdrawal effects have never been documented in RCTs evaluating OXN PR 16,19,20,53 . Additional longterm studies with PR OXN combination in patients with NP are required to better understand the benefits and risk of this treatment.…”

“…Naloxone, following oral administration, acts almost exclusively on opioid receptors in the GI tract; due to the extensive first-pass hepatic metabolism, its systemic bioavailability is however very low, without affecting the central analgesic activity of oxycodone. There is robust evidence that PR OXN is effective in reducing OIBD, while maintaining analgesia in patients with chronic pain of noncancer and cancer aetiology -RCTs and post-marketing observations have documented the efficacy and safety of PR OXN combination, with an improvement in bowel function and a substantial reduction in the use of laxatives [16][17][18][19] . Improved QoL and reduced GI events with PR OXN combination may lead to better cost effectiveness compared with oxycodone monotherapy 38 .…”

“…Because naloxone has a marked first-pass hepatic metabolism, its systemic bioavailability after oral administration is exceedingly low (53%), and the systemic exposure is insufficient to inhibit the central, pain-relieving action of oxycodone 12 . The new OXN formulation has been documented, both in RCTs and in observational studies, as providing analgesic efficacy while improving OIBD and a consequent decrease in the use of rescue medications and laxatives [16][17][18][19][20] . OXN, licensed since 2006 in Germany for the treatment of severe pain, which can only be adequately managed with opioid analgesics, is currently marketed in several other European countries.…”