Setipiprant,a Selective Oral Antagonist of Human CRTH2: Relative Bioavailability of a Capsule and a Tablet Formulation in Healthy Female and Male Subjects

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/m². 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 C_max (0.94; 95% CI, 0.79–1.12) and AUC_0–∞ (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 C_max (capsules: 1.01; 95% CI, 0.71–1.44; tablet: 0.89; 95% CI, 0.62–1.26) and AUC_0–∞ (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.