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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

This Phase II study has shown that using a new sustained release formulation to deliver oral naloxone to the colon allows successful treatment of OIC without comprising the desired opioid effects.

Background and aim Strong opioids including oxycodone are amongst the most effective analgesics to combat moderate to severe pain of various aetiologies, but opioid-induced bowel dysfunction (OIBD) represents a relevant problem. The rationale for development of a prolonged-release (PR) fixed combination of oxycodone and naloxone was to counteract OIBD. Due to its negligible oral bioavailability, the μ-opioid receptor antagonist naloxone is able to selectively displace opioids from local μ-receptors in the gastrointestinal tract without affecting central opioid binding sites. Pivotal trials of PR oxycodone/naloxone not only demonstrated improved bowel function but also equivalent analgesic efficacy compared to PR oxycodone alone. Controlled clinical trials comparing PR oxycodone/naloxone with strong opioids other than oxycodone are not available. The present study is the first data set aimed at comparing pain control, bowel function, and quality of life (QoL) in patients newly treated with or switched to PR oxycodone/naloxone or other strong opioids during routine clinical practice. Methods In this three-arm, prospective observational study, 588 patients with moderate to severe pain of varying aetiologies received either PR oxycodone/naloxone (OXN group and OXN 40/20 group with indicated use of the 40 mg/20 mg dose strength at baseline) or other strong opioids (control group), dosed according to pain severity, for 4-6 weeks. Data documented include pain intensity (NRS), bowel function (Bowel Function Index, BFI), pain-related functional impairment (BPI-SF), QoL (EuroQol EQ-5D-3L), and a global assessment of treatment. Results Patients receiving PR oxycodone/naloxone experienced a clinically important reduction in pain intensity and pain-related functional impairment of approximately 40%. The reductions of pain intensity (-2.9 ± 2.3) and pain-related functional impairment (-2.4 ± 2.3) in the OXN group were significantly more pronounced than in the control group (-2.1 ± 2.1 and -1.8 ± 1.7). In the control group, mean reductions in pain intensity did not reach the threshold of ≥30% for at least moderate clinically important differences, although patients were prescribed higher doses of morphine equivalents than OXN group patients. Improvements in bowel function (OXN: -16.0 ± 27.6; control: 3.1 ± 24.4) and QoL (OXN: 20.8 ± 24.2; control: 13.2 ± 23.1) were also significantly more pronounced in the OXN group, with BFI scores reduced to a level that reflects normal bowel function. Results for the OXN 40/20 group receiving higher doses of PR oxycodone/naloxone were in line with those for the OXN group. In the control group, more frequent gastrointestinal adverse events and less favourable ratings of tolerability resulted in a higher rate of treatment discontinuations due to adverse events. Conclusions In patients receiving PR oxycodone/naloxone, more favourable outcomes compared with other strong opioids regarding pain control, bowel function, and QoL were observed. Implications The present findings underline the value of...