Effect of elagolix exposure on clinical efficacy endpoints in phase 3 trials in women with endometriosis-associated pain: An application of Markov model.

Elagolix is an oral gonadotropin-releasing hormone antagonist approved by the US FDA for treatment of endometriosis with associated moderate to severe pain. The objective of this work was to characterize the relationships between elagolix exposures and clinical efficacy response rates for dysmenorrhea (DYS) and non-menstrual pelvic pain (NMPP) in women enrolled in the pivotal phase 3 studies with endometriosis with associated moderate to severe pain. Relationships between elagolix average concentrations (Cavg ) and efficacy responses (DYS and NMPP) were characterized using a nonlinear mixed-effects discrete-time first order Markov modeling approach. Only age was statistically significant for NMPP but not considered clinically relevant. This work indicates that the selection of elagolix dose is not determined based on tested patient demographics, baseline or endometriosis disease severity measures in covariate analysis. In other words, the work suggests no preference of one regimen over the other to treat endometriosis-associated pain (DYS or NMPP) for any patient subpopulation based on tested covariate groups.