Effects of Intranasal Corticosteroid and Montelukast On Nasal Allergen Challenges*

The primary goal of this proposal is to assess the ability of an intranasal corticosteroid,
fluticasone, and montelukast to affect the upper airway and systemic physiologic, biologic
and clinical parameters occurring after an early and late upper airway allergic response to
ragweed in ragweed allergic rhiniticsThe assessment of early allergy responses in the nose
has been fairly well established in our laboratory and we will use methods detailed in
previous publications (21, 23 24). One potential challenge will be to sample upper airway
mediators and cytokines without affecting clinical parameters such as symptom scores and
acoustic rhinometry readings. Moreover, we will need to sample at time points throughout six
or more hours in order to accurately determine the effects on late phase allergic responses.
Nasal filter paper sampling is a technique that we are currently engaged in using, and we
will work with Roche to elute the samples and measure multiple mediators and cytokines.

Inclusion Criteria:

- Male or female subjects aged 19-60 years.

- Females of child bearing potential must use appropriate birth control throughout the
study and urine pregnancy tests must be negative prior to dosing at each study visit.

- Subjects with a documented history of ragweed-induced seasonal allergic rhinitis
requiring pharmacotherapy during the preceding 2 allergen seasons.

- Subjects with a positive skin prick test to short ragweed (Amb a 1) extract, defined
as >3mm wheal larger than saline control

- Subjects spirometry FEV1 must be > 80% predicted prior to each allergen challenge

- Subjects average post diluents nasal congestion score must be < 1 at admission for
each study visit

Exclusion Criteria:

- Subjects with evidence or history of clinically significant medical illnesses other
than changes related to allergic rhinitis. Subjects with some stable chronic medical
conditions not expected to interfere with the conduct or safety of the study may be
eligible to participate based on the investigator's discretion.

- Subjects with a history of asthma or urticaria, or a screening FEV1 prior to allergen
challenge of <80% of predicted. in FEV1 compared to pre-diluent FEV1 baseline at
either screening visit.

- Subjects with significant nasal deformity, recent nasal surgery nasal polyps or
chronic rhinosinusitis.

- Subjects who have smoked in the last 6 months or have a history of >10 pack years.

- Subjects who are taking or have taken restricted concomitant medications that could
confound the safety or efficacy assessments including those shown below.

- Subjects who have history or evidence of alcohol or drug abuse.

- Subjects exposed to cat and have a positive skin test to cat.

- Subjects that have a positive skin test to dust mite (D pteronyssinus/ D farinae)
requiring pharmacotherapy