Source: Annual Congress 2010 - New treatments for asthma and COPD
Disease area: Airway diseases

Abstract

Rationale: AMG 853 is a potent, selective, orally bioavailable small molecule that inhibits binding of prostaglandin D2 (PGD₂) to its two receptors: chemoattractant receptor-homologous molecule expressed on T helper lymphocyte type 2 cells (CRTH2) and D-prostanoid (DP). PGD₂ induces a variety of biological actions including eosinophil infiltration, vasodilation, and bronchoconstriction.
Methods: In this randomized, double-blind, placebo-controlled study, 82 subjects received AMG 853 (5-400 mg) or placebo oral solution. Solid, oral doses of AMG 853 (25 mg) were administered to 12 subjects. Safety, tolerability, pharmacokinetic, and pharmacodynamic data were obtained.
Results: No deaths, treatment-related serious adverse events, or study discontinuations due to adverse events were reported in the AMG 853-treated subjects. Adverse events (in ≥2 subjects) in any treatment group included abdominal pain, contact dermatitis, headache, and catheter site hematoma. AMG 853 pharmacokinetics was approximately dose-proportional over the 5-400 mg dose range. Formation of AMG 853 glucuronide, the major circulating metabolite, was observed in all subjects. Pharmacodynamic data showed that AMG 853 effectively antagonized ex vivo PGD₂ responses mediated by CRTH2 and DP receptors, and attenuated niacin-induced flushing, which is partially mediated by PGD₂.
Conclusion: In this first-in-human study in healthy subjects, AMG 853 was well tolerated at all administered doses.

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Citations should be made in the following way:
C. Banfield, J. Parnes, M. Emery, L. Ni, N. Zhang, P. Hodsman (Thousand Oaks, Seattle, United States Of America; Melbourne, Australia). Single-dose, first-in-human study of AMG 853: Pharmacokinetics, pharmacodynamics, and safety in healthy adults. Eur Respir J 2010; 36: Suppl. 54, 1164

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