Setipiprant, a selective oral antagonist of human CRTH2: relative bioavailability of a capsule and a tablet formulation in healthy female and male subjects.
Clin Ther
; 35(11): 1842-8, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-24095247
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 (11 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Prostaglandina
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Receptores Imunológicos
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Indóis
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Naftalenos
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
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Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article