Efficacy and Safety of Oxycodone/Naloxone Controlled Release in Comparison with Oxycodone Controlled Release in Korean Patients with Cancer Pain

Abstract

ABSTRACT Aim: Oxycodone/naloxone controlled release (CR) was developed for the management of opioid-induced constipation through the local antagonistic effect of naloxone in the gut wall, while maintaining analgesia due to low bioavailability of oral naloxone. We compared the efficacy and safety of oxycodone/naloxone CR with oxycodone CR in Korean cancer pain patients. Methods: We enrolled the patients with cancer pain who had NRS score ≥4 (Numeric Rating Scale 0-10) and needed strong opioid therapy in a randomized, multicenter, open label, non-inferiority, phase IV study. The initial dose of oxycodone/naloxone CR was 20/10 mg per day which could be up-titrated according to investigator's opinion to a maximum of 80/40 mg per day. The primary outcome was the difference in NRS score at 4 weeks from baseline by intention-to-treat analysis, and the margin of non-inferiority was set to be 1.5. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) and bowel habit change were also evaluated as the secondary outcomes. Results: Total 132 patients were enrolled and 128 (64 patients in each group), 117 (58 in oxycodone/naloxone CR group) patients were included in safety set and full analysis set, respectively. The mean daily doses of oxycodone/naloxone CR and oxycodone CR group were 29.7 ± 15.2 and 26.9 ± 13.8 mg, respectively. In full analysis set, the difference in NRS at 4 weeks from baselines between the treatments with oxycodone/naloxone CR and oxycodone CR was -0.027, with the two-sided 95% confidence interval (CI) ranged from -0.830 to 0.776. The upper boundary of the 95% CI was below the margin of 1.5, confirming the non-inferiority of oxycodone/naloxone CR to oxycodone CR (p = 0.0001). The results of EORTC QLQ-C30 and bowel habit change showed that there were no statistically significant differences between the two groups. The incidence of adverse drug reactions (ADRs) was 38/64 (59.4%) in oxycodone/naloxone CR group and 41/64 (64.1%) in oxycodone CR group (p = 0.5850). Conclusions: Oxycodone/naloxone CR was non-inferior to oxycodone CR for controlling cancer pain in Korean patients with similar incidence of ADRs. Disclosure: J. Kang: this study was sponsored by Mundipharma Korea LTD.; B.S. Kim: This study was sponsored by Mundipharma Korea Ltd.; J. Jin: This study was sponsored by Mundipharma Korea Ltd.; J.H. Kwon: This study was sponsored by Mundipharma Korea Ltd.; I. Woo: This study was sponsored by Mundipharma Korea Ltd.; Y. Ko: This study was sponsored by Mundipharma Korea Ltd.; S. Park: This study was sponsored by Mundipharma Korea Ltd.; H.Y. Kim: This study was sponsored by Mundipharma Korea Ltd. HY Kim is Medical Manager of the company.