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Bimosiamose, an inhaled small-molecule pan-selectin antagonist, attenuates late asthmatic reactions following allergen challenge in mild asthmatics: a randomized, double-blind, placebo-controlled clinical cross-over-trial.
Pulm Pharmacol Ther. 2006; 19(4):233-41.PP

Abstract

BACKGROUND

Asthma is characterized by increased recruitment of inflammatory cells from the circulation into the airways. As selectins mediate tethering and rolling of leukocytes on the vascular endothelium, they constitute a promising target for the therapeutic modulation of inflammation. We evaluated the effect of inhaled bimosiamose (TBC1269), a synthetic pan-selectin antagonist, on allergen-induced late asthmatic reactions (LAR) in mild asthmatics.

METHODS

Twelve male subjects with mild allergic asthma (only beta-agonists prn) with demonstrable LAR (fall of FEV1 3-8h after allergen inhalation >15% of baseline) at screening completed a randomized, double-blind, placebo-controlled clinical cross-over-trial. Subjects were treated with inhaled bimosiamose 70 mg bid or matching placebo on days 1-3 and 70 mg once on the morning of day 4. On day 4 following the last inhalation of study drug, an allergen challenge was performed. The primary endpoint was the maximum fall in FEV1 between 3 and 8h after allergen inhalation on active treatment vs. placebo. Secondary endpoints included early asthmatic response, exhaled nitric oxide, and airway hyperresponsiveness to methacholine 24h post allergen.

RESULTS

Bimosiamose significantly attenuated the maximum LAR compared to placebo by 50.2% (placebo mean+/-SEM fall -13.10+/-2.30%, bimosiamose -6.52+/-3.86%, treatment effect p=0.045; linear mixed-effects model). There was no effect of active treatment on early asthmatic response, post allergen airway hyperresponsiveness or exhaled nitric oxide, and peripheral blood cells.

CONCLUSIONS

Administration of the pan-selectin antagonist bimosiamose is effective in a human allergen challenge model of asthma. The result of this proof-of-concept exploratory trial is the first study that demonstrates clinical efficacy of selectin-antagonists as novel therapeutic strategy in asthma.

Authors+Show Affiliations

Pulmonary Department, Internal Medicine, University Hospital, Mainz, Germany. k.beeh@insaf-wi.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16140027

Citation

Beeh, Kai M., et al. "Bimosiamose, an Inhaled Small-molecule Pan-selectin Antagonist, Attenuates Late Asthmatic Reactions Following Allergen Challenge in Mild Asthmatics: a Randomized, Double-blind, Placebo-controlled Clinical Cross-over-trial." Pulmonary Pharmacology & Therapeutics, vol. 19, no. 4, 2006, pp. 233-41.
Beeh KM, Beier J, Meyer M, et al. Bimosiamose, an inhaled small-molecule pan-selectin antagonist, attenuates late asthmatic reactions following allergen challenge in mild asthmatics: a randomized, double-blind, placebo-controlled clinical cross-over-trial. Pulm Pharmacol Ther. 2006;19(4):233-41.
Beeh, K. M., Beier, J., Meyer, M., Buhl, R., Zahlten, R., & Wolff, G. (2006). Bimosiamose, an inhaled small-molecule pan-selectin antagonist, attenuates late asthmatic reactions following allergen challenge in mild asthmatics: a randomized, double-blind, placebo-controlled clinical cross-over-trial. Pulmonary Pharmacology & Therapeutics, 19(4), 233-41.
Beeh KM, et al. Bimosiamose, an Inhaled Small-molecule Pan-selectin Antagonist, Attenuates Late Asthmatic Reactions Following Allergen Challenge in Mild Asthmatics: a Randomized, Double-blind, Placebo-controlled Clinical Cross-over-trial. Pulm Pharmacol Ther. 2006;19(4):233-41. PubMed PMID: 16140027.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Bimosiamose, an inhaled small-molecule pan-selectin antagonist, attenuates late asthmatic reactions following allergen challenge in mild asthmatics: a randomized, double-blind, placebo-controlled clinical cross-over-trial. AU - Beeh,Kai M, AU - Beier,Jutta, AU - Meyer,Michael, AU - Buhl,Roland, AU - Zahlten,Rainer, AU - Wolff,Gerhard, Y1 - 2005/09/01/ PY - 2004/10/05/received PY - 2005/05/19/revised PY - 2005/07/07/accepted PY - 2005/9/6/pubmed PY - 2006/12/13/medline PY - 2005/9/6/entrez SP - 233 EP - 41 JF - Pulmonary pharmacology & therapeutics JO - Pulm Pharmacol Ther VL - 19 IS - 4 N2 - BACKGROUND: Asthma is characterized by increased recruitment of inflammatory cells from the circulation into the airways. As selectins mediate tethering and rolling of leukocytes on the vascular endothelium, they constitute a promising target for the therapeutic modulation of inflammation. We evaluated the effect of inhaled bimosiamose (TBC1269), a synthetic pan-selectin antagonist, on allergen-induced late asthmatic reactions (LAR) in mild asthmatics. METHODS: Twelve male subjects with mild allergic asthma (only beta-agonists prn) with demonstrable LAR (fall of FEV1 3-8h after allergen inhalation >15% of baseline) at screening completed a randomized, double-blind, placebo-controlled clinical cross-over-trial. Subjects were treated with inhaled bimosiamose 70 mg bid or matching placebo on days 1-3 and 70 mg once on the morning of day 4. On day 4 following the last inhalation of study drug, an allergen challenge was performed. The primary endpoint was the maximum fall in FEV1 between 3 and 8h after allergen inhalation on active treatment vs. placebo. Secondary endpoints included early asthmatic response, exhaled nitric oxide, and airway hyperresponsiveness to methacholine 24h post allergen. RESULTS: Bimosiamose significantly attenuated the maximum LAR compared to placebo by 50.2% (placebo mean+/-SEM fall -13.10+/-2.30%, bimosiamose -6.52+/-3.86%, treatment effect p=0.045; linear mixed-effects model). There was no effect of active treatment on early asthmatic response, post allergen airway hyperresponsiveness or exhaled nitric oxide, and peripheral blood cells. CONCLUSIONS: Administration of the pan-selectin antagonist bimosiamose is effective in a human allergen challenge model of asthma. The result of this proof-of-concept exploratory trial is the first study that demonstrates clinical efficacy of selectin-antagonists as novel therapeutic strategy in asthma. SN - 1094-5539 UR - https://www.unboundmedicine.com/medline/citation/16140027/Bimosiamose_an_inhaled_small_molecule_pan_selectin_antagonist_attenuates_late_asthmatic_reactions_following_allergen_challenge_in_mild_asthmatics:_a_randomized_double_blind_placebo_controlled_clinical_cross_over_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1094-5539(05)00080-5 DB - PRIME DP - Unbound Medicine ER -