Mast cell inhibitor R112 is well tolerated and affects prostaglandin D-2 but not other mediators, symptoms, or nasal volumes in a nasal challenge model of allergic rhinitis

National Research Center (CO, USA), Boulder, Colorado, United States
Allergy and Asthma Proceedings (Impact Factor: 3.06). 05/2006; 27(3):208-13. DOI: 10.2500/aap.2006.27.2861
Source: PubMed


Understanding of the role played by mast cells in allergic rhinitis (AR) has led to the development of novel therapies. The aim of this study was to determine the safety and tolerability of R112, an inhibitor of the tyrosine kinase Syk, in an allergen challenge model of AR. We also examined the effects of R112 on symptoms, mediator release, and nasal airway volumes. This double-blinded, randomized, placebo-controlled, crossover trial enrolled 20 out-of-season volunteers with AR. One intranasal dose of R112 or vehicle was administered and followed by an allergen challenge. In addition to safety monitoring, symptoms; changes in histamine, tryptase, and prostaglandin D2 (PGD2) content of nasal secretions; and acoustic rhinometry were determined over a 15-minute period. R112 was well tolerated. Adverse events were similar between treatments. Five minutes after allergen instillation, PGD2 was decreased when subjects received R112 compared with vehicle (93.4 +/- 23.0 pg/mL versus 171.6 +/- 23.0 pg/mL; p = 0.03), and this correlated with rhinorrhea (p = 0.05). However, at 10 minutes, changes in PGD2, tryptase, and histamine were not significant (46.8 +/- 9.2 pg/mL versus 68.6 +/- 9.2 pg/mL, p = 0.1; 9.5 +/- 2.7 ng/mL versus 16.6 +/- 2.9 ng/mL, p = 0.09; and 1.5 +/- 1.6 ng/mL versus 3.5 +/- 1.6 ng/mL, p = 0.4). No differences were found in symptoms or in acoustic rhinometry between treatment groups. Single-dose R112 appears safe and significantly reduces PGD2 but not histamine or tryptase release in response to allergen challenge in subjects with AR.

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    • "Syk inhibition has tried in patients suffering of allergic disorders to determine whether it mitigates clinical manifestations. A nasal allergen challenge study in volunteers with allergic rhinitis showed that one intranasal dose of R112 is clinically safe and significantly reduces the level of prostaglandin D2, a key mediator of allergic nasal congestion, but not histamine and tryptamine levels [54]. In this 2-day, multiple-dose, double-blind, placebo-controlled clinical study with seasonal allergic rhinitis patients, R112 significantly decreased the global clinical symptom score compared with placebo. "
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