An intranasal Syk-kinase inhibitor (R112) improves the symptoms of seasonal allergic rhinitis in a park environment.

Abstract

R112 inhibits Syk kinase, a transducer of signaling through the Fcepsilon receptor of mast cells, blocking mast cell responses to allergic stimuli. Examine the efficacy and safety of intranasal R112 in volunteers with symptomatic seasonal allergic rhinitis compared with a placebo in a park setting. In this double-blind, placebo-controlled study of 319 volunteers with seasonal allergic rhinitis, 160 were randomized to intranasal R112 and 159 to a vehicle control during 2 days at 2 separate locations in spring 2004. Subjects were evaluated for symptoms of allergic rhinitis (i.e., sneezes, runny nose/sniffles, itchy nose, stuffy nose) on the basis of a possible maximum score of 32 for the Global Symptom Complex (GSC) scale. The primary outcome evaluated was the difference in the reduction in GSC (area under the curve over a period of 8 hours) from baseline between R112 and vehicle placebo. At baseline, the combined GSC was approximately 18/32 and equal between treatment groups. After 8 hours (dosing 3 mg/nostril every 4 hours x 2), R112 significantly reduced the GSC compared with placebo (7 vs 5.4 units, respectively; P = .0005). Each individual symptom combined to form the GSC was also significantly improved in the R112 group compared with control ( P < .05). As early as 45 minutes after dosing, R112 showed a significant improvement in symptoms over placebo, and the duration of action exceeded 4 hours. Adverse effects were indistinguishable between the groups and clinically insignificant. Intranasal R112 was effective in this park study and is a promising new treatment for seasonal allergic rhinitis.