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

Abstract

Introduction: AZD9668 is an oral inhibitor of Neutrophil Elastase (NE), an enzyme implicated in the signs, symptoms and disease progression in COPD via its role in matrix degradation, the inflammatory process and mucus hypersecretion. Aims: To evaluate the safety, tolerability and pharmacokinetics (PK) of AZD9668 in healthy subjects and patients with COPD. Methods: Three double-blind, placebo-controlled studies were completed (Table 1). PK parameters and the effect of AZD9668 on ex vivo zymosan-stimulated NE activity in whole blood were assessed. Results: AZD9668 was generally well tolerated. PK in Japanese subjects and COPD patients were similar to Caucasian subjects. PK was dose linear; t_max was reached at 1-2 h and the short elimination t_1/2 (~6 h) was consistent with bid dosing. Steady state was reached by Day 2 of bid dosing with negligible accumulation; ~40% of AZD9668 was eliminated renally as unchanged compound. Ex vivo inhibition of NE activity was dose dependent, with maximal inhibition at 60 mg. Conclusions: AZD9668 was well tolerated at single doses up to 150 mg and multiple doses up to 70 mg bid in these studies. The PK of AZD9668 was linear and maximal inhibition of NE activity was achieved at doses ≥60 mg.

AZD9668 studies

Study	D0520C00001	D0520C00004	D0520C00002
Subjects	Healthy Caucasian (n=75)	Healthy Caucasian and Japanese (n=32)	COPD (n=18)
Dosing regimen: single doses	2-150 mg	30-120 mg	--
Dosing regimen: repeated doses	30-120 mg od for 8 days	30 and 70 mg bid for 6.5 days	60 mg bid 14 days

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Citations should be made in the following way:
K. Gunawardena, H. Gullstrand, J. Perrett (Loughborough, United Kingdom; Lund, Sweden). Safety, tolerability and pharmacokinetics of AZD9668, an oral neutrophil elastase inhibitor, in healthy subjects and patients with COPD. Eur Respir J 2010; 36: Suppl. 54, 1163

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