Naldemedine is effective in the treatment of opioid-induced constipation in patients with chronic non-cancer pain who had a poor response to laxatives

Abstract

Background: Two studies demonstrated the efficacy and safety of naldemedine in adult patients with chronic non-cancer pain and opioid-induced constipation (OIC). However, no studies have compared the efficacy of peripherally acting µ-opioid receptor antagonists in patients with adequate and inadequate responses to prior OIC therapy with laxatives. This post hoc analysis of integrated data from the two previous studies compared the efficacy of naldemedine in patients who were unsuccessfully treated with laxatives [poor laxative responders (PLRs)] with those who either did not receive laxatives >30\u2009days prior to screening or those who only received rescue laxative at or after screening (non-PLRs). Methods: Patients with OIC were randomized to once-daily treatment with naldemedine 0.2\u2009mg or placebo. The primary efficacy endpoint was the proportion of responders [⩾3 spontaneous bowel movements (SBMs)/week and an increase from baseline of ⩾1 SBM/week for ⩾9\u2009weeks of the 12-week treatment period and ⩾3\u2009weeks of the final 4\u2009weeks of the 12-week treatment period]. Additional endpoints included change in SBM frequency, change in frequency of SBMs without straining, proportion of complete SBM (CSBM) responders, change in CSBM frequency, and time to first SBM. Treatment-emergent adverse events (TEAEs) were assessed. Results: The analysis included 538 (317 PLRs, 221 non-PLRs) and 537 (311 PLRs, 226 non-PLRs) patients in the naldemedine and placebo arms, respectively. There were significantly more responders in the naldemedine PLR (46.4%; p\u2009<\u20090.0001) and non-PLR (54.3%; p\u2009=\u20090.0009) subgroups versus the placebo groups (30.2% and 38.9%, respectively). In both the PLR and non-PLR subgroups, naldemedine treatment was superior to placebo on all additional endpoints. Overall incidence of TEAEs in the PLR subgroups treated with naldemedine or placebo was similar. Conclusion: This integrated analysis further supports the efficacy and tolerability of naldemedine in the treatment of OIC and demonstrates a consistent effect in both PLR and non-PLR subgroups. [ClinicalTrials.gov identifier: NCT01965158 and NCT01993940]