The effect of IVX-0142, a heparin-derived hypersulfated disaccharide, on the allergic airway responses in asthma |
| |
Authors: | Duong M Cockcroft D Boulet L-P Ahmed T Iverson H Atkinson D C Stahl E G Watson R Davis B Milot J Gauvreau G M O'Byrne P M |
| |
Institution: | McMaster University, Hamilton, ON;;University of Saskatchewan, Saskatoon, SK;;Institut de cardiologie et de pneumologie de l'UniversitéLaval, Hôpital Laval, Québec, QC, Canada;;Mount Sinai Medical Centre, Miami Beach;;IVAX Research Inc., Miami, FL, USA |
| |
Abstract: | Background: IVX-0142 is a heparin-derived hypersulfated disaccharide devoid of anticoagulant activity while possessing anti-allergic and anti-inflammatory activity in preclinical studies. In a proof-of-concept study, the allergen inhalation challenge model was used to investigate the effect of IVX-0142 in mild atopic asthma. Methods: Nineteen subjects, not on controller medications, were randomized to an evaluator-blind, placebo-controlled, cross-over study. The effect of a single nebulized dose of IVX-0142 (80 mg) or placebo administered 30 min prior to allergen inhalation was evaluated on the allergic airway responses, airway responsiveness, and airway inflammation. Results: When compared with placebo, 14 and 13 subjects experienced a relatively smaller maximum fall in forced expiratory volume in 1 s (maxFEV1%) for the early airway response (EAR) and late airway response (LAR) with IVX-0142, respectively ( P < 0.01). The degree of attenuation in the EAR maxFEV1% (mean ± SE) 26.5 ± 2.8% vs placebo 31.0 ± 2.8%, P = 0.059] and LAR (15.6 ± 2.9% vs placebo 19.0 ± 2.9%, P = 0.24) with IVX-0142, however, was small and did not reach statistical significance compared with placebo. Similarly, a trend in the attenuation of allergen-induced increase in the absolute sputum cell counts was also observed. No difference in the allergen-induced increase in airway hyper-responsiveness and exhaled nitric oxide was noticed. Conclusions: The majority of mild atopic asthmatics demonstrated a reduction in the EAR and LAR to IVX-0142. However, the treatment effect observed with a single prechallenge dose of IVX-0142 was small and heterogeneous. The potential anti-allergic and anti-inflammatory effects using multiple higher doses need to be evaluated. |
| |
Keywords: | anti-allergic anti-inflammatory asthma heparin derivative |
本文献已被 PubMed 等数据库收录! |
|