Therapeutic Control of Aspirin-Exacerbated Respiratory Disease With Ifetroban

The protocol involves a 4-week, double-blind, placebo-controlled parallel-design trial of
oral ifetroban in patients with AERD. At the end of the 4-week treatment phase (ifetroban or
placebo) each subject will undergo a graded oral aspirin desensitization procedure in order
to initiate high-dose aspirin therapy, which is standard-of-care at our institution and is
the only available therapy known to modify the course of AERD.

Inclusion Criteria:

1. History of AERD, defined as meeting the diagnostic triad with:

- History of physician-diagnosed asthma and

- History of physician-diagnosed nasal polyposis and

- History of pathognomonic reactions aspirin or other nonselective COX inhibitors.

2. Stable asthma (post-bronchodilator FEV1 of ≥70%, no glucocorticoid burst for at least
2 weeks prior to Visit 1, and no hospitalizations or ER visits for asthma for at least
the prior 6 months)

3. Age between 18 and 65 years

4. No current smoking (not more than one instance of smoking in the last 3 months)

5. Non-pregnant

Exclusion Criteria:

1. Hypersensitivity to montelukast

2. Current use of zileuton

3. History of bleeding diathesis or use of anticoagulant or antiplatelet drugs

4. Current use of any NSAIDs aside from the aspirin provided during the study

5. Current use of beta blockers

6. Use of any biologics within the last 4 months prior to initiating the study