Population Exposure‐Response Modeling of Naloxegol in Patients With Noncancer‐Related Pain and Opioid‐Induced Constipation

摘要

Naloxegol is a polyethylene glycol derivative of naloxone approved in the US as a once‐daily oral treatment for opioid‐induced constipation (OIC) in adults with chronic noncancer pain. Population exposure–response models were constructed based on data from two phase III studies comprising 1,331 adults with noncancer pain and OIC. In order to characterize the protocol‐defined naloxegol responder rate, the number of daily spontaneous bowel movements (SBMs) was characterized by a longitudinal ordinal nonlinear mixed‐effects logistic regression dose–response model, and the incidence of diary entry discontinuation was described by a time‐to‐event model. The mean number of SBMs per week increased with increasing naloxegol dose. The predicted placebo‐adjusted responder rates (90% confidence interval) were 10.4% (4.6–13.4%) and 11.1% (4.8–14.4%) for naloxegol 12.5 and 25 mg/day, respectively. Model‐predicted response to naloxegol was influenced by the baseline SBM frequency and characteristics of the opioid treatment.