Trial to Determine the Safety of Oral Ifetroban in Patients With a History of Aspirin Exacerbated Respiratory Disease
Condition: Aspirin Exacerbated Respiratory Disease (AERD)
MeSH terms: Respiratory Tract Diseases; Respiration Disorders
Intervention: Ifetroban, Oral Capsule; Placebo, Oral Capsule
Intervention MeSH terms: Ifetroban
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Samster's triad; Acetylsalicylic acid triad; Widal's triad; Francis' triad; Aspirin triad; Aspirin-induced asthma and rhinitis (AIAR)

Summary:

      The primary objective of the study is to determine the safety of oral ifetroban compared to
      placebo as measured by a > 20% decrease in FEV1 compared to baseline following a dose of
      Investigational Medicinal Product (IMP) (Study Day 1 or 2) prior to initiation of the aspirin
      challenge.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Adults with a history of physician-diagnosed stable asthma (FEV1 of at least 1.25
             liters and 60% or better than predicted* on two previous visits with no more than a
             10% variation in those values, no increase in baseline dose of oral glucocorticoids
             for asthma for at least three months, and no history of hospitalization or emergency
             room visits for asthma for at least the prior six months).

          2. Have a history of nasal polyposis.

          3. Have a history of at least one clinical reaction to oral aspirin or other nonselective
             cyclooxygenase (COX) inhibitor with features of lower (cough, chest tightness,
             wheezing, dyspnea) and/or upper (rhinorrhea, sneezing, nasal obstruction, conjunctival
             itching and discharge) airway involvement.

          4. Currently receiving montelukast (at least 10 mg per day, oral) or Zafirlukast (at
             least 20 mg twice per day, oral), with at least 1 week of therapy prior to first dose
             of IMP.

        Exclusion Criteria:

          1. Be less than 18 years of age or greater than or equal to 65 years of age.

          2. Be pregnant, nursing, or planning to become pregnant.

          3. Be a current tobacco smoker (defined as a daily tobacco smoker during any of the six
             months preceding this study or more than one instance of tobacco smoking in the last
             three months).

          4. Use of a beta blocker in the last week.

          5. Use of an antihistamine in the 48 hours prior to the first dose of IMP.

          6. Use of nasal decongestants in the 48 hours prior to the first dose of IMP.

          7. Use of aspirin or non-steroidal inflammatory drug (NSAID) in the last two weeks.

          8. Use of zileuton in the last two weeks.

          9. Have required one or more doses of ≥ 40 mg prednisone or equivalent in the last two
             weeks.

         10. Have a history of systemic or life-threatening respiratory reaction to aspirin
             requiring intubation or administration of epinephrine.

         11. Have a history of peptic ulcer disease, gastrointestinal bleed, or current severe
             gastro-esophageal reflux disease (GERD), defined as a patient currently requiring more
             than two total doses of medication per day to treat persistent symptoms: either more
             than two doses of any single medication type (antacid, proton pump inhibitor, or H2
             receptor antagonist), or more than 2 types of medication per day to treat symptoms.

         12. Have a history of tolerating a COX-1 blocking drug after their history of a
             respiratory reaction to a similar drug.

         13. Have a history of cardiovascular disease including myocardial infarction, heart
             failure, atrial or ventricular rhythm disturbances, or angina, or a previous abnormal
             electrocardiogram.

         14. Have a history of bleeding diathesis or use of anticoagulant or antiplatelet drugs in
             the last two weeks.

         15. Have a history of allergy or hypersensitivity to ifetroban.

         16. Have taken investigational drugs within 30 days before IMP administration.

         17. Inability to understand the requirements of the study, inability to understand spoken
             English and abide by the study restrictions and to return for the required treatments
             and assessments.

         18. Be otherwise unsuitable for the study, in the opinion of the investigator.