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 receptors CRTH2 and DP. A first-in-human study showed that AMG 853 was well tolerated as a single, oral dose in healthy subjects.
Objective: To evaluate the safety and tolerability of multiple, oral doses of AMG 853 in healthy adult subjects.
Methods: In this randomized, double-blind, placebo-controlled, ascending-dose study, AMG 853 was administered in a tablet formulation for 14 consecutive days. Forty eight subjects were randomized to receive twice daily AMG 853 (5-100 mg), once daily AMG 853 (100, 200 mg), or placebo. Safety, tolerability, pharmacokinetic, and pharmacodynamic data were obtained.
Results: No deaths, serious adverse events, investigational product withdrawals or study discontinuations due to adverse events (AEs) were reported. The incidence of AEs did not appear to increase with increasing AMG 853 dose and was no different in the AMG 853 cohorts (33%-67%) vs. placebo (58%). AMG 853 was rapidly absorbed with no unexpected accumulation after repeated dosing in all treatment groups. Major circulating metabolite, AMG 853 glucuronide formation was observed in all cohorts. Antagonist effect on both CRTH2 and DP receptors in the ex vivo setting was demonstrated at steady state trough concentrations.
Conclusion: In healthy, adult subjects, AMG 853 was well tolerated at all administered doses. AMG 853 effectively antagonized the ex vivo PGD₂-mediated signaling by CRTH2 and DP receptors.

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Citations should be made in the following way:
J. Parnes, C. Banfield, V. Chow, N. Zhang, P. Hodsman (Thousand Oaks, United States Of America; Melbourne, Australia). Multiple-dose study of AMG 853 in healthy adults: Safety and pharmacokinetics. Eur Respir J 2010; 36: Suppl. 54, 1165

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