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

• Published in: Clinical therapeutics Vol. 35; no. 11; pp. 1842 - 1848
• Main Authors: Baldoni, Daniela, PhD, Mackie, Alison, MSc, Gutierrez, Marcelo, PhD, Theodor, Rudolf, MD, Dingemanse, Jasper, PhD
• Format: Journal Article
• Language: English
• Published: Bridgewater, NJ EM Inc USA 01.11.2013; Elsevier; Elsevier Limited
• Subjects: Administration, Oral; Adolescent; Adult; Allergies; Asthma; Biological and medical sciences; Biological Availability; Capsules; Chemistry, Pharmaceutical; Cross-Over Studies; CRTH2; Drug dosages; Drug therapy; Female; Gender differences; human pharmacokinetics; Humans; Indoles - administration & dosage; Indoles - adverse effects; Indoles - pharmacokinetics; Internal Medicine; Male; Medical Education; Medical sciences; Middle Aged; Naphthalenes - administration & dosage; Naphthalenes - adverse effects; Naphthalenes - pharmacokinetics; Pharmaceuticals; Pharmacology. Drug treatments; Plasma; Receptors, Immunologic - antagonists & inhibitors; Receptors, Prostaglandin - antagonists & inhibitors; relative bioavailability; setipiprant; Studies; Tablets; Therapeutic Equivalency; Womens health; Young Adult; relative bioavailability; CRTH2; setipiprant; human pharmacokinetics; Human; Healthy subject; Setipiprant; Oral administration; Chemoattractant receptor homologous molecule expressed on Th2; Capsule; Bioavailability; Formulation; Dosage form; Tablet; Antagonist; Pharmacokinetics
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2013.09.003

Abstract 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 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.