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

Lynn Webster, MD, Raj Tummala, MD, MBA, MS, Ulysses Diva, PhD, Jaakko Lappalainen, MD, PhD

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.


Keywords


constipation, naloxegol, opioid-induced constipation, opioid receptor antagonist, safety, tolerability

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References


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DOI: https://doi.org/10.5055/jom.2016.0360

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