Naloxegol (Movantik®) Provides Rapid Response and Sustained Improvement of Opioid-Induced Constipation Symptoms in Older Adults

Abstract

Naloxegol (Movantik®), an oral peripherally acting mu-opioid receptor antagonist (PAMORA) has demonstrated rapid and predictable relief of OIC in patients treated with opioids for chronic non-cancer pain in two phase 3 trials (KODIAC 4/5; NCT01309841/NCT01323790). In subjects ≥65 yrs, naloxegol (25mg, 12.5mg) demonstrated significantly better response rates, clinically relevant early symptom relief, and predictable efficacy compared with PBO. Improvements in SBMs, CSBMs, straining, and stool consistency were rapid and sustained across 12 weeks. Naloxegol is effective and safe in individuals ≥65 yrs with non-cancer pain experiencing OIC.Aim: Naloxegol, an oral peripherally acting mu-opioid receptor antagonist (PAMORA) has demonstrated rapid and predictable relief of opioid-induced constipation (OIC) in patients treated with opioids for chronic non-cancer pain in two phase 3 trials (KODIAC 4/5; NCT01309841/NCT01323790). This analysis evaluates the speed and predictability of response, and the rapid and sustained impact of naloxegol on OIC symptoms in subjects aged ≥65 yrs. Methods: Data were pooled from the KODIAC 4/5 intent-to-treat populations (N=1337). Subjects ≥65 yrs treated once daily with naloxegol 25mg, 12.5mg, or placebo (PBO) were evaluated. Response definition: ≥3 SBM/wk and increase of ≥1 SBM/wk over baseline for ≥9 of 12 weeks, and ≥3 of the final 4 weeks. For each SBM, patients documented complete evacuation (CSBM) (Yes/No), degree of straining (scale 1=not at all, 5=extreme), and stool consistency via the Bristol Stool Scale (1=hard, 7=watery). Results: This analysis evaluated 148 subjects ≥65 yrs (11.1% of the overall population). In these older adults, a significantly higher response rate was achieved with naloxegol (25mg, 50.9%, p=0.037; 12.5mg, 53.3%; p=0.036) vs PBO (32.0%). Corresponding HRs (2.52, p< 0.001; 1.90, p=0.005) indicated significant, ∼two-fold reduction in time to first SBM with naloxegol vs PBO. Time to first CSBM was ∼50% shorter for naloxegol vs PBO for both regimens (Hazard Ratios: 1.66, p=0.019; 1.45, p=0.103). Rapid, statistically significant, and clinically relevant symptom improvement (straining and stool consistency) was generally sustained from weeks 1-12 for naloxegol vs PBO. The most common AEs were GI-related and similar across regimens. Conclusion: In subjects ≥65 yrs, naloxegol (25mg, 12.5mg) demonstrated significantly better response rates, clinically relevant early symptom relief, and predictable efficacy compared with PBO. Improvements in SBMs, CSBMs, straining, and stool consistency were rapid and sustained across 12 weeks. Naloxegol is effective and safe in individuals ≥65 yrs with non-cancer pain experiencing OIC.