Naldemedine in Japanese patients with opioid-induced constipation and chronic noncancer pain: open-label Phase III studies.

Introduction: Naldemedine is a peripherally-acting mu-opioid-receptor antagonist, approved in Japan for opioid-induced constipation (OIC). In two open-label, single-arm, Phase III studies, we evaluated the safety and efficacy of naldemedine in Japanese patients with OIC receiving regular-use opioids (COMPOSE-6) or prolonged-release oxycodone (COMPOSE-7) for chronic noncancer pain. Methods: Eligible Japanese adults with OIC and chronic noncancer pain received once-daily oral naldemedine 0.2 mg for 48 weeks, irrespective of food intake. Primary end points included measures of treatment-emergent adverse events (TEAEs), pain intensity, and opioid withdrawal. Secondary efficacy end points were evaluated at treatment week 2. Patient Assessment of Constipation Symptoms (PAC-SYM) and Quality of Life (PAC-QOL) scores were evaluated in both 48-week studies. Results: Of patients enrolled in COMPOSE-6 (N = 43) and COMPOSE-7 (N = 10), TEAES were reported in 88% (95% CI 74.9-96.1) and 90% (95% CI 55.5-99.7), respectively. The most frequently reported TEAEs, nasopharyngitis and diarrhea, were mostly mild or moderate in severity. Assessments of pain intensity and opioid withdrawal remained stable over the 48-week treatment periods of both studies. The proportion of spontaneous bowel-movement responders at week 2 in COMPOSE-6 was 81.0% (95% CI 65.9-91.4) and 90.0% (95% CI 55.5-99.7) in COMPOSE-7. Significant and sustained improvements in PAC-SYM and PAC-QOL scores were also observed in both studies (all P<0.05). Conclusion: Side effects that occurred with naldemedine were mostly mild or moderate in severity, and the data suggested that naldemedine can improve bowel function and QOL in Japanese patients with OIC receiving regular-use opioids or prolonged-release oxycodone for chronic noncancer pain.