Naloxegol for Treating Opioid-Induced Constipation n Patients with Non-Cancer Pain (S710)

Abstract

•Become familiar with the safety and efficacy profile of naloxegol as a treatment for opioid-induced constipation in patients with chronic non-cancer pain.•Understand the mechanism of action of peripherally acting mu-opioid receptor antagonists and how this method of action differs from that of standard laxatives. Opioid-induced constipation (OIC) affects 40%–80% of patients receiving opioids to manage chronic non-cancer pain, which can negatively impact quality of life and effective pain management. OIC results when opioid agonist effects at mu-opioid receptors in the enteric nervous system reduce gastrointestinal (GI) transit and secretions. Over-the-counter laxatives are often ineffective. Naloxegol is an approved, orally administered, peripherally acting mu-opioid receptor antagonist (PAMORA) that specifically targets the mechanism of OIC. To summarize phase 3 clinical trial data for naloxegol. Data were reviewed from two phase 3 randomized, double-blind, 12-week studies conducted in outpatients with non-cancer pain and OIC (KODIAC-04, [NCT01309841]; KODIAC-05, [NCT01323790]) and a 52-week, phase 3 safety study (KODIAC-08 [NCT01336205]). KODIAC-04 (n=652) and KODIAC-05 (n=700) compared the efficacy (primary endpoint: response over 12 weeks) and safety of daily administration of naloxegol 12.5 or 25 mg vs. placebo. A key secondary endpoint included the 12-week response rate in laxative users with OIC symptoms. Both studies reported significantly higher response rates for naloxegol 25 mg vs. placebo in the overall population and among laxative users with OIC symptoms. KODIAC-08 (n=844) compared the safety and tolerability of naloxegol with usual care, and demonstrated a long-term safety profile similar to that seen in the 12-week studies. In all three studies, most common adverse events (AEs) on naloxegol were GI AEs, which occurred early in treatment, were mild or moderate in severity, and resolved during treatment or after discontinuation. Pain scores and opioid doses remained stable. The mechanism of action of naloxegol will be discussed. Naloxegol is a safe and efficacious treatment for OIC in adults with chronic non-cancer pain.