Efficacy and safety of controlled-release oxycodonealoxone versus controlled-release oxycodone in Korean patients with cancer-related pain: a randomized controlled trial

摘要

Background Controlled-release oxycodonealoxone (OXN-CR) maintains the effect of opioid-induced analgesia through oxycodone while reducing the occurrence rate of opioid-induced constipation through naloxone. The present study was designed to assess the non-inferiority of OXN-CR to controlled-release oxycodone (OX-CR) for the control of cancer-related pain in Korean patients. Methods In this randomized, open-labeled, parallel-group, phase IV study, we enrolled patients aged 20?years or older with moderate to severe cancer-related pain [numeric rating scale (NRS) pain score ≥4] from seven Korean oncology/hematology centers. Patients in the intention-to-treat (ITT) population were randomized (1:1) to OXN-CR or OX-CR groups. OXN-CR was administered starting at 20?mg/10?mg per day and up-titrated to a maximum of 80?mg/40?mg per day for 4?weeks, and OX-CR was administered starting at 20?mg/day and up-titrated to a maximum of 80?mg/day for 4?weeks. The primary efficacy endpoint was the change in NRS pain score from baseline to week 4, with non-inferiority margin of ?1.5. Secondary endpoints included analgesic rescue medication intake, patient-reported change in bowel habits, laxative intake, quality of life (QoL), and safety assessments. Results Of the ITT population comprising 128 patients, 7 with missing primary efficacy data and 4 who violated the eligibility criteria were excluded from the efficacy analysis. At week 4, the mean change in NRS pain scores was not significantly different between the OXN-CR group ( n =?58) and the OX-CR group ( n =?59) (?1.586 vs. ?1.559, P =?0.948). The lower limit of the one-sided 95% confidence interval (?0.776 to 0.830) for the difference exceeded the non-inferiority margin ( P Conclusions OXN-CR was non-inferior to OX-CR in terms of pain reduction after 4?weeks of treatment and had a similar safety profile. Studies in larger populations of Korean patients with cancer-related pain are needed to further investigate the effectiveness of OXN-CR for long-term pain control and constipation alleviation. Trial registration ClinicalTrials.gov NCT01313780, registered March 8, 2011