A 12-week extension study to assess the safety and tolerability of naloxegol in patients with noncancer pain and opioid-induced constipation.

ABSTRACT

OBJECTIVE: To compare the long-term safety and tolerability of naloxegol with placebo in patients with opioid-induced constipation (OIC) and noncancer pain. DESIGN: Twelve-week, multicenter, randomized, double-blind, parallel-group phase 3 extension study (KODIAC-07, NCT01395524). SETTING: Clinical investigation centers in the United States. PATIENTS Adult outpatients (N = 302) with confirmed OIC who had completed a 12-week pivotal phase 3 study (KODIAC-04, NCT01309841). INTERVENTIONS: Daily oral administration of naloxegol (12.5 and 25 mg) or placebo. MAIN OUTCOME MEASURES: Adverse events (AEs), including treatment-related AEs, serious AEs, and AEs of special interest; changes from baseline to week 12 in pain scores, daily opioid dose, and symptoms and quality-of-life measurements. RESULTS: No important new AEs occurred during this extension study compared with KODIAC-04. AEs occurred more frequently with naloxegol 25 mg (41.2 percent) versus naloxegol 12.5 mg (34.0 percent) and placebo (33.0 percent). Treatment-emergent AEs occurring in >5 percent of patients in either naloxegol group during the treatment period were arthralgia (25 mg; 5.2 percent) and diarrhea (12.5 mg; 5.3 percent); two reported AEs attributable to opioid withdrawal syndrome in naloxegol groups were deemed unrelated to study medication. None of the gastrointestinal serious AEs was adjudicated as bowel perforation; one patient (naloxegol 12.5 mg) had an event adjudicated as a major cardiovascular event and was unrelated to study medication. Pain scores and daily opioid dose were unchanged, and improvements in symptoms and quality-of-life observed in KODIAC-04 were maintained throughout the extension study. CONCLUSION: Naloxegol was generally safe and well tolerated in this 12-week extension study in patients with noncancer pain and OIC.