Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis.

Background: Eosinophilic esophagitis (EoE) is a chronic allergic disease with limited treatment options.

Objective: We evaluated QAX576, an mAb against IL-13, in the treatment of patients with EoE.

Methods: Patients (18-50 years) with proton pump inhibitor-resistant esophageal eosinophilia received intravenous QAX576 (6 mg/kg) or placebo (2:1) at weeks 0, 4, and 8 and were followed for 6 months.

Phase II study of a neutrophil elastase inhibitor (AZD9668) in patients with bronchiectasis.

Unlabelled: Neutrophil elastase (NE) activity is increased in bronchiectasis and may play a role in this condition. We wished to determine the effect of AZD9668, a selective oral inhibitor of NE. Efficacy and safety of AZD9668 60 mg twice daily over 4 weeks were evaluated in a randomised, double-blind, placebo-controlled, parallel-group, Phase II, signal-searching study in patients with bronchiectasis.

Pharmacokinetics and safety of AZD9668, an oral neutrophil elastase inhibitor, in healthy volunteers and patients with COPD.

Objective: To establish the pharmacokinetics (PK), tolerability and safety profile of AZD9668, an oral inhibitor of neutrophil elastase (NE), an enzyme implicated in the signs, symptoms and disease progression in NE-driven respiratory diseases via its role in the inflammatory process, mucus overproduction and lung-tissue damage.

Methods: PK and safety/tolerability profile of AZD9668 were studied in 107 healthy Caucasian and Japanese volunteers and 18 patients with COPD in three double-blind, randomized, placebo-controlled studies with single and multiple exposure to AZD9668 for up to 14 days. Ex vivo zymosan-stimulated NE activity in whole blood was also assessed as a surrogate pharmacodynamic measure.

A randomised, placebo-controlled, dose-finding study of AZD9668, an oral inhibitor of neutrophil elastase, in patients with chronic obstructive pulmonary disease treated with tiotropium.

AZD9668 is a fully reversible, selective, oral inhibitor of neutrophil elastase, a protease implicated in chronic obstructive pulmonary disease (COPD). Efficacy, safety and tolerability of AZD9668 (5, 20 and 60 mg bid) were compared with placebo in a randomised, double-blind, placebo-controlled, 12-week, Phase IIb trial (NCT00949975: approved by an Investigational Review Board), in patients with symptomatic COPD receiving maintenance tiotropium. The primary endpoint was pre-bronchodilator forced expiratory volume in 1 second (FEV₁).

Efficacy, safety and effect on biomarkers of AZD9668 in cystic fibrosis.

The aim of this study was to evaluate the safety and effect on clinical outcomes and biomarkers of inflammation and tissue damage of the neutrophil elastase inhibitor AZD9668 (60 mg twice daily orally for 4 weeks) in cystic fibrosis. This was a randomised, double-blind, placebo-controlled study. Primary outcome measures were sputum neutrophil count, lung function, 24-h sputum weight, BronkoTest® diary card data and health-related quality-of-life (revised cystic fibrosis quality-of-life questionnaire).

Influence of ethnic origin and sex on the pharmacokinetics of clazosentan.

This study investigated the influence of ethnic origin and, as a secondary objective, sex on the pharmacokinetics of the parenteral endothelin receptor antagonist clazosentan in healthy Caucasian and Japanese subjects. Twelve subjects of each ethnic origin (female/male ratio 1:1) were treated with sequential 4-hour infusions of 1, 5, and 15 mg/h. Blood samples were taken frequently to determine plasma levels of clazosentan.

Comparison of the pharmacokinetics, pharmacodynamics and tolerability of tezosentan between caucasian and Japanese subjects.

Aim: To investigate the pharmacokinetics, pharmacodynamics and tolerability of the dual endothelin receptor antagonist tezosentan in caucasian and Japanese subjects.

Methods: Twelve subjects of each ethnic origin were treated in a double-blind, randomized design with sequential 3-h infusions of 2.5, 5.

Safety of unoprostone isopropyl 0.15% ophthalmic solution in patients with mild to moderate asthma.

Purpose: To assess the safety of unoprostone isopropyl 0.15% ophthalmic solution (UIOS) in patients with mild to moderate asthma.

Methods: Randomized, double-masked, two-period crossover, placebo-controlled study comparing unoprostone 0.