Background: CRTH2 is a prostaglandin D2 receptor that plays an important role in allergic inflammation. Setipiprant is a potent CRTH2 antagonist under development for the treatment of allergic diseases.
Objective: The aim of this study was to evaluate the tolerability and pharmacokinetics of a single oral dose of a setipiprant capsule (reference) and a tablet formulation.
Methods: This was an open-label, 2-period, 2-way crossover, randomized study in which 20 healthy women and men (1:1 ratio) received either 2 250-mg capsules or a 500-mg tablet of setipiprant. Subjects were between 18 and 45 years old, with a body mass index of 18.0 to 28.0 kg/m(2). Differences in pharmacokinetics of setipiprant formulations were explored overall and by sex.
Results: All subjects completed the study. Both formulations were well tolerated, with headache the most frequently reported adverse event (25% of subjects), followed by flatulence (15%) and somnolence and fatigue (10%). The adverse event profile in men and women and between formulations was similar. The ratios of geometric means for Cmax (0.94; 95% CI, 0.79-1.12) and AUC0-∞ (1.01; 95% CI, 0.92-1.12) were mostly within the limits of 0.80 to 1.25. When corrected for weight, the differences observed between sexes, within each treatment, for Cmax (capsules: 1.01; 95% CI, 0.71-1.44; tablet: 0.89; 95% CI, 0.62-1.26) and AUC0-∞ (capsules: 1.12; 95% CI, 0.86-1.47; tablet: 0.96; 95% CI, 0.73-1.25) were minor.
Conclusion: Both the setipiprant formulations were well tolerated. Setipiprant pharmacokinetics were similar between formulations, overall, and between sexes. The new tablet formulation may constitute a valid alternative to the capsule formulation for later clinical development phases. ClinicalTrials.gov identifier: NCT01877629.
Keywords: CRTH2; human pharmacokinetics; relative bioavailability; setipiprant.
Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.