Long-term evaluation of combined prolonged-release oxycodone and naloxone in patients with moderate-to-severe chronic pain: Pooled analysis of extension phases of two Phase III trials

Abstract

Background: While opioids provide effective analgesia, opioid-induced constipation (OIC) can severely impact quality of life and treatment compliance. This pooled analysis evaluated the maintenance of efficacy and safety during long-term treatment with combined oxycodone/naloxone prolonged-release tablets (OXN PR) in adults with moderate-to-severe chronic pain. Methods: Patients (N = 474) received open-label OXN PR during 52-week extension phases of two studies, having completed 12-week, double-blind, randomized treatment with oxycodone prolonged-release tablets (Oxy PR) or OXN PR. Analgesia and bowel function were assessed at each study visit using 'Average pain over last 24 h scale and Bowel Function Index (BFI), respectively. Treatment Satisfaction Questionnaire for Medication was assessed at study end only. Key Results: Improvement in bowel function was particularly marked in patients who switched from Oxy PR in the double-blind phase to OXN PR during the extension phase, resulting in a clinically meaningful reduction (≥12 points) in BFI score: at the start of the extension phases, mean (SD) BFI score was 44.3 (28.13), and was 29.8 (26.36) for patients who had received OXN PR in the double-blind phase. One week later, BFI scores were similar for the two groups (26.5 [24.40] and 27.5 [25.60], respectively), as was observed throughout the following months. Fewer than 10% of patients received laxatives regularly. Mean 24-h pain scores were low and stable throughout the extension phases. No unexpected adverse events were observed. Conclusions & Inferences: Pooled data demonstrate OXN PR is an effective long-term therapy for patients with chronic non-cancer pain, and can address symptoms of OIC. No new safety issues were observed which were attributable to the long-term administration of OXN PR. Pooled data from the 12-month extension phases of two Phase III trials demonstrate combined oxycodone/naloxone prolonged-release tablets (OXN PR) are an effective long-term therapy for patients with chronic non-cancer pain, and can address symptoms of opioid-induced constipation. Comparable pain control but with improved bowel function was observed with OXN PR vs oxycodone PR and was maintained during the open-label, long-term treatment. No new safety issues were observed which were attributable to the long-term administration of OXN PR. aScreening and double-blind phases: patients who required laxatives (patients provided with bisacodyl by the study investigator, according to the study protocol). bExtension phases: patients who used laxatives regularly (according to specific dosing and treatment instructions provided by the investigator). cNo study treatment was received during Screening. At Run-in, patients had prestudy opioid converted to open-label Oxy PR, titrated to an effective analgesic dose.