A Phase 2b, Randomized, Double-Blind Placebo-Controlled Study to Evaluate the Efficacy and Safety of Naldemedine for the Treatment of Opioid-Induced Constipation in Patients with Chronic Noncancer Pain
Abstract Objective This 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. Methods This four-week, phase 2b, randomized, double-blind placebo-controlled trial...
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Published in | Pain medicine (Malden, Mass.) Vol. 18; no. 12; pp. 2350 - 2360 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
England
Oxford University Press
01.12.2017
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Subjects | |
Online Access | Get full text |
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Summary: | Abstract
Objective
This 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.
Methods
This 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.
Results
Overall, 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.
Conclusion
Naldemedine 0.2 mg once daily is the optimal dose for future confirmatory trials in OIC. |
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Bibliography: | Previous Presentation of Data: Results from this study were presented in poster format at PAINWeek 2015, September 8–12, 2015, Las Vegas, Nevada, USA. Disclosures: LRW has received honoraria for consultancy from AstraZeneca, BioDelivery Sciences International, CVS Caremark, Grünenthal USA, Mallinckrodt Pharmaceuticals, Nevro Corporation, and Synchrony Healthcare; for advisory board attendance from Depomed, Egalet, Inspirion Pharmaceuticals, Insys Therapeutics, Kaleo, Mallinckrodt Pharmaceuticals, Orexo, Proove Biosciences, Signature Therapeutics, Teva Pharmaceuticals, and Trevena; and for travel expenses from AstraZeneca, BioDelivery Sciences International, Bristol-Myers Squibb, Depomed, Grünenthal USA, Inspirion Pharmaceuticals, Insys Therapeutics, Jazz Pharmaceuticals, Kaleo, Mallinckrodt Pharmaceuticals, Nektar Therapeutics, Nevro Corporation, Orexo, Proove Biosciences, and Trevena. TY and JCAF are employees of Shionogi, Inc. Funding sources: This research was funded by Shionogi & Co., Ltd., Osaka, Japan. |
ISSN: | 1526-2375 1526-4637 |
DOI: | 10.1093/pm/pnw325 |