Evaluating Factors Involved in Dymista's Superior Clinical Efficacy to Fluticasone Propionate in the Treatment of Seasonal Allergic Rhinitis

The main hypothesis for the trial is that Dymista affects multiple phases of the allergic
response, which in sum are greater than the effects of fluticasone propionate or azelastine
hydrochloride alone.

Our objectives for this study are to demonstrate:

1. that the induction of allergic inflammation by nasal provocation with antigen causes a
cellular infiltration, with subsequent release of inflammatory biomarkers that cause
augmented responses to subsequent exposure to antigens.

2. that fluticasone prevents allergic inflammation from developing after antigen challenge
and subsequently prevents the augmentation of the nasal response to nasal challenge
with antigen.

3. that the azelastine in Dymista reduces the effects of released histamine

To address these hypotheses we will perform a 3-way, randomized, placebo-controlled, and
crossover trial. We will recruit 20 asymptomatic seasonal allergic rhinitis patients outside
of the relevant season. The subjects will receive placebo, fluticasone propionate and
Dymista. The nasal provocations will be separated by 2 weeks. Treatment will begin 15
minutes before nasal provocation with ragweed or grass antigen and the treatment will
continue twice a day for 3 days. Nasal provocation will occur daily for three days to
evaluate for priming (increased sensitization with repeated antigen exposure, which mimics
seasonal disease where antigen exposure occurs in the setting of continued allergic
inflammation). For outcome measures, we will monitor both nasal symptoms after nasal
provocation as well as collect nasal lavage to evaluate effects on eosinophils and
biomarkers of the immune response. In the nasal lavage, we will quantify the number of
eosinophils (a marker of cellular recruitment) and measure the levels of histamine (a marker
of basophil and mast cell activation), tryptase (a marker of mast cell activation), albumin
(a marker of vascular permeability), lactoferrin (a marker of glandular activation) and ECP
(a marker of eosinophil activation). Thus we expect to generate information on both clinical
effects and physiologic differences between the treatments.

Inclusion Criteria:

1. Males and females between 18 and 55 years of age.

2. History of grass and/or ragweed allergic rhinitis.

3. Positive skin test to grass and/or ragweed antigen.

4. Positive response to screening nasal challenge.

5. Off all anti-allergic medications for a minimum of 2 weeks.

Exclusion Criteria:

1. Physical signs or symptoms suggestive of renal, hepatic or cardiovascular disease.

2. Pregnant or lactating women.

3. Upper respiratory infection within 14 days of study start.