Efficacy and safety of naloxegol for opioid-induced constipation assessed by specific opioid medication, opioid dose, and duration of opioid use.

ABSTRACT

OBJECTIVE: Efficacy and safety of naloxegol, a peripherally acting µ-opioid receptor antagonist that significantly reduces opioid-induced constipation (OIC), were assessed for patient subgroups defined post hoc by baseline maintenance opioid characteristics. DESIGN: Post hoc, pooled analysis of data from two 12-week, randomized, double-blind, placebo-controlled, phase 3 studies. SETTING: Two hundred fifty-seven outpatient centers in the United States and Europe. PATIENTS Patients with noncancer pain and OIC. INTERVENTIONS: Naloxegol (12.5 or 25 mg daily) or placebo. MAIN OUTCOMES MEASURES: The primary efficacy endpoint was the proportion of patients meeting response criteria at 12 weeks at least three spontaneous bowel movements (SBMs)/wk and an increase from baseline of at least one SBM for ≥9 of 12 weeks and ≥3 of the last 4 weeks. No adjustments were made for multiplicity; all p values are descriptive. RESULTS: This analysis included 1,337 patients. Increases in the proportion of patients who achieved response at 12 weeks were observed with naloxegol 25 mg versus placebo in patients taking maintenance oxycodone, hydrocodone, morphine, or fentanyl (p ≤ 0.038); patients taking either ≥120 or <120 morphine-equivalent units at baseline (p ≤ 0.032); and patients treated with their current opioid for >6 months (p ≤ 0.035). Efficacy results were less robust with naloxegol 12.5 mg versus placebo. Adverse event incidences were generally comparable across treatment groups, regardless of opioid dose or duration of therapy but were numerically higher with some specific baseline opioids. CONCLUSION: In this post hoc, exploratory analysis, naloxegol 25 mg showed similar efficacy in treating OIC regardless of maintenance opioid type, dose, or duration of opioid use at baseline.