Treatment with Naloxegol Versus Placebo: Pain Assessment in Patients with Noncancer Pain and Opioid‐Induced Constipation

Objective To summarize results from pain and opioid use assessments with naloxegol in adults with opioid‐induced constipation ( OIC ) and chronic noncancer pain. Methods Two phase 3 randomized, double‐blind, 12‐week studies evaluated the efficacy and safety of oral naloxegol (12.5 or 25 mg daily) in adults (18 to < 85 years) with confirmed OIC and chronic noncancer pain: KODIAC ‐04 ( NCT 01309841) and KODIAC ‐05 ( NCT 01323790). Pain level was assessed daily (11‐point numeric rating scale [ NRS ]; 0 = no pain, 10 = worst imaginable pain). Changes from baseline in mean weekly pain scores and opioid dose (weeks 1 through 12) were analyzed using mixed‐model repeated measures. Results At baseline, mean daily NRS average pain scores ranged from 4.5 to 4.8 for all groups in KODIAC ‐04 ( N = 652) and were 4.6 for each group in KODIAC ‐05 ( N = 700). Respective mean ± SD changes from baseline average pain for placebo, naloxegol 12.5 mg, and naloxegol 25 mg were −0.2 ± 1.07, −0.3 ± 1.05 ( P = 0.773 vs. placebo), and 0.2 ± 0.95 ( P = 0.837 vs. placebo; KODIAC ‐04) and −0.1 ± 0.94, −0.1 ± 0.87 ( P = 0.744), and 0.0 ± 1.18 ( P = 0.572; KODIAC ‐05). At baseline, mean daily opioid doses ranged from 135.6 to 143.2 morphine equivalent units ( MEU s)/day in KODIAC ‐04, and from 119.9 to 151.7 MEU s/day in KODIAC ‐05. Respective mean ± SD changes from baseline dose were −1.8 ± 30.19, −2.3 ± 20.52 ( P = 0.724 vs. placebo), and 0.4 ± 13.01 ( P = 0.188 vs. placebo; KODIAC ‐04) and −0.3 ± 17.14, −1.3 ± 17.11 ( P = 0.669 vs. placebo), and 0.1 ± 8.54 ( P = 0.863 vs. placebo; KODIAC ‐05). Changes in maintenance opioid dose were few; reasons for such changes were similar across treatment groups. Conclusion Centrally mediated opioid analgesia was maintained during treatment with naloxegol in patients with noncancer pain and OIC .