Naloxegol was shown to maintain adequate opioid analgesia over a 12-week treatment course, while relieving opioid-induced constipation, in a recent study published in Pain Practice.1
In two phase 3 studies (ClinicalTrials.gov identifiers: NCT01309841 for KODIAC-04 [n=652] and NCT01323790 for KODIAC-05 [n=700]), researchers evaluated the safety and efficacy of oral naloxegol 12.5 mg or 25 mg over 12 weeks in adults with chronic noncancer pain and confirmed opioid-induced constipation. To determine whether adequate opioid analgesia was maintained throughout the treatment, pain levels were assessed daily on an 11-point Numeric Rating Scale. Mean weekly pain scores were calculated and used for analysis.
Mean baseline pain scores across groups ranged from 4.5 to 4.8 for KODIAC-04 and KODIAC-05. In the KODIAC-04 trial, mean changes in pain scores from baseline were not significantly different for naloxegol 12.5 mg (mean±SD: -0.3±1.05; P =.77) or for naloxegol 25 mg (0.2±0.95; P =.84) compared with placebo (-0.2±1.07). Similarly, in the KODIAC-05 trial, no significant difference was noted for naloxegol 12.5 mg (-0.1±0.87; P =.74) and naloxegol 25 mg (0.0±1.18; P =.57) compared with placebo (-0.1±0.94).
Changes in mean daily opioid doses from baseline were not significantly different for the naloxegol groups compared with placebo in KODIAC-04 or in KODIAC-05.
During the studies, changes in patients’ maintenance doses were uncommon. Reasons for changes were similar across groups, with the most common reason being inadequate pain control.
Andrew Fariello, PharmD, Vice President of US Medical Affairs at AstraZeneca, explained that the study results are “consistent with the peripheral site of action of naloxegol.” He concluded that “naloxegol does not have a clinically relevant effect on patient-reported pain levels or mean daily opioid dose in patients with non-cancer pain and [opioid-induced constipation]. In parallel, changes in maintenance opioid dose were few and not clinically relevant.”
Webster L, Diva U, Tummala R, Sostek M. Treatment with naloxegol versus placebo: Pain assessment in patients with noncancer pain and opioid-induced constipation [published online September 12, 2017]. Pain Pract. doi: 10.1111/papr.12640