Efficacy and safety of naloxegol in patients with opioid-induced constipation and laxative-inadequate response.

ABSTRACT

BACKGROUND: Treatment options for patients with opioid-induced constipation (OIC) and inadequate response to laxatives (LIR) are few. OBJECTIVE: Assess the efficacy and safety of orally administered naloxegol in patients with prospectively confirmed OIC and LIR. METHODS: We analyzed pooled data from two identical randomized, double-blind, placebo-controlled, Phase 3 trials of naloxegol in patients with non-cancer pain, OIC and LIR in which naloxegol (12.5 mg, n = 240; 25 mg, n = 241) or placebo (n = 239) were administered daily. We assessed the response rates, time to first post-dose laxation, spontaneous bowel movements (SBMs), OIC symptoms and patient-reported outcomes over 12 weeks. RESULTS: OIC response rates for the naloxegol 25-mg (p < 0.001) and the 12.5-mg (p = 0.005) LIR dose groups were higher than placebo. Median times to first post-dose SBM were 7.6, 19.2 and 41.1 hours for the naloxegol 25 mg, naloxegol 12.5 mg and placebo groups, respectively. Other SBM measures, daily symptoms of OIC, and both the Patient Assessment of Constipation - Symptoms and Patient Assessment of Constipation-Quality of Life scores improved from baseline with naloxegol treatment. Changes from baseline in opioid dose, pain scores and opioid withdrawal scores were similar among treatment groups. CONCLUSIONS: Naloxegol was efficacious, generally safe and well tolerated in the patients with OIC and LIR, while preserving opioid analgesia. ClinicalTrials.gov identifiers NCT01309841; NCT01323790.