The Oral Bioavailability and Effect of Various Gastric Conditions on the Pharmacokinetics of Dersimelagon in Healthy Adult Volunteers

Dersimelagon is a novel orally administered selective agonist for melanocortin receptor 1 being investigated for the treatment of erythropoietic protoporphyria, X‐linked protoporphyria, and diffuse cutaneous systemic sclerosis. In this open‐label, multicenter, randomized, two‐cohort, sequential crossover study, the relative oral bioavailability of two tablet formulations of dersimelagon was evaluated, and the effect of various gastric conditions (from a high‐fat meal, a proton‐pump inhibitor, and an acidic carbonated beverage) on the pharmacokinetics of dersimelagon were assessed in healthy participants (N = 50). Both tablet formulations demonstrated rapid absorption, and the 100‐mg tablets showed a 97% relative oral bioavailability versus 50‐mg tablets. No effect was observed on overall exposure (area under the plasma concentration versus time curve [AUC]) following consumption of a high‐fat meal, and Cmax was higher (22%, 90% confidence interval [CI] 1.05–1.42) in a fed state compared with fasted conditions. Similarly, overall exposure AUC of dersimelagon was comparable following administration alone or in combination with esomeprazole; however, coadministration of esomeprazole led to a slight decrease in Cmax (fasted: 9%, 90%CI 0.77–1.07; fed: 24%, 90%CI 0.66–0.88) compared with administration of dersimelagon alone. In general, the consumption of an acidic beverage increased time to Cmax regardless of fed or fasted status and decreased overall exposure AUC and Cmax of dersimelagon.