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 C 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 C (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 C regardless of fed or fasted status and decreased overall exposure AUC and C of dersimelagon.