• Lynn R Webster, Tadaaki Yamada, and Arjona FerreiraJuan CamiloJCShionogi, Inc., Clinical Development, Florham Park, New Jersey, USA..
• PRA Health Sciences, Early Development Services, Salt Lake City, Utah.
• Pain Med. 2017 Dec 1; 18 (12): 2350-2360.

ObjectiveThis study evaluated the efficacy and safety of oral naldemedine 0.1 mg, 0.2 mg, or 0.4 mg once daily in patients who had opioid-induced constipation (OIC) and maintained a stable laxative regimen.MethodsThis four-week, phase 2b, randomized, double-blind placebo-controlled trial (clinicaltrials.gov identifier NCT01443403) enrolled patients on long-term opioid therapy for chronic noncancer pain with OIC. The primary efficacy end point was change in weekly spontaneous bowel movement (SBM) frequency from baseline to the last two weeks of treatment. Secondary end points included the proportion of SBM responders (patients with ≥3 SBMs/week and an increase of ≥1 SBM/week from baseline over the last 2 weeks of treatment). Safety parameters assessed included adverse events, effects on analgesia, and opioid withdrawal symptoms.ResultsOverall, 244 patients were randomized 1:1:1:1 to naldemedine 0.1 mg, 0.2 mg, 0.4 mg, or placebo. Baseline patient characteristics were comparable. Weekly SBM frequency was significantly higher with naldemedine 0.2 mg (3.37, P = 0.0014) and 0.4 mg (3.64, P = 0.0003), but not with 0.1 mg (1.98, P = 0.3504), vs placebo (1.42). The proportion of SBM responders was significantly higher with naldemedine 0.2 mg (71.2%, P = 0.0005) and 0.4 mg (66.7%, P = 0.003), but not with 0.1 mg (52.5%, P = 0.1461), vs placebo (39.3%). Treatment-emergent adverse events were generally mild to moderate in severity; incidences increased with naldemedine dose. No clinically meaningful changes in other safety parameters were observed.ConclusionNaldemedine 0.2 mg once daily is the optimal dose for future confirmatory trials in OIC.© 2017 American Academy of Pain Medicine.

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