Trial to Determine the Safety of Oral Ifetroban in Patients With a History of Aspirin Exacerbated Respiratory Disease

Study Overview
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Brief Summary
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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.

Official Title
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A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial to Determine the Safety of Oral Ifetroban in Patients With a History of Aspirin Exacerbated Respiratory Disease

Conditions
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Aspirin Exacerbated Respiratory Disease (AERD)

Intervention / Treatment
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* Drug: Ifetroban, Oral Capsule
* Drug: Placebo, Oral Capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). Have a history of nasal polyposis. 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. 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: Be less than 18 years of age or greater than or equal to 65 years of age. Be pregnant, nursing, or planning to become pregnant. 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). Use of a beta blocker in the last week. Use of an antihistamine in the 48 hours prior to the first dose of IMP. Use of nasal decongestants in the 48 hours prior to the first dose of IMP. Use of aspirin or non-steroidal inflammatory drug (NSAID) in the last two weeks. Use of zileuton in the last two weeks. Have required one or more doses of ≥ 40 mg prednisone or equivalent in the last two weeks. Have a history of systemic or life-threatening respiratory reaction to aspirin requiring intubation or administration of epinephrine. 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. Have a history of tolerating a COX-1 blocking drug after their history of a respiratory reaction to a similar drug. Have a history of cardiovascular disease including myocardial infarction, heart failure, atrial or ventricular rhythm disturbances, or angina, or a previous abnormal electrocardiogram. Have a history of bleeding diathesis or use of anticoagulant or antiplatelet drugs in the last two weeks. Have a history of allergy or hypersensitivity to ifetroban. Have taken investigational drugs within 30 days before IMP administration. 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. Be otherwise unsuitable for the study, in the opinion of the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Ifetroban, Oral Capsule<br>Ifetroban, Oral Capsule; 200 mg per dose (four - 50 mg capsules), once per day on Study Days 1, 2, and 3. | Drug: Ifetroban, Oral Capsule<br> <br> |
| Placebo Comparator: Placebo, Oral Capsule<br>Placebo, Oral Capsule; matching capsules for oral ifetroban dosing, four capsules once per day on Study Days 1, 2, and 3. | Drug: Placebo, Oral Capsule<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Who Experience a ≥ 20% Decrease in Forced Expiratory Volume in One Second (FEV1) Compared to Baseline Following a Dose of Investigational Medicinal Product (IMP) (Study Day 1 or 2) Prior to Initiation of the Aspirin Challenge |  | Study Day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients With a ≥ 25% Decrease in Peak Nasal Inspiratory Flow Rate Compared to Baseline Following a Dose of IMP (Study Day 1 or 2) Prior to Initiation of the Aspirin Challenge |  | Up to Study Day 2 | 
| Proportion of Patients With a ≥ 25% Increase in Total Nasal Symptom Score (TNSS) Compared to Baseline Following a Dose of IMP (Study Day 1 or 2) Prior to Initiation of the Aspirin Challenge |  | Up to Study Day 2 | 
| Incidence and Severity of Treatment-emergent Adverse Events |  | Up to Study Day 7 | 
| Proportion of Patients Who Experience a ≥ 20% Decrease in FEV1 Compared to Baseline During the Aspirin Challenge |  | Study Day 2 and 3 | 
| Proportion of Patients With a ≥ 25% Decrease in Peak Nasal Inspiratory Flow Rate (NIFR) Compared to Baseline During the Aspirin Challenge |  | Study Day 2 and 3 | 
| Proportion of Patients With a ≥ 25% Increase in TNSS Compared to Baseline During the Aspirin Challenge |  | Study Day 2 and 3 | 
| Amount of Rescue Medication Required During the Aspirin Challenge | The amount of rescue medication required during the aspirin challenge | Study Day 2 and 3 | 
| Incidence and Severity of Asthmatic Reactions During the Treatment Period |  | Study Day 1 through 3 | 
| Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg. |  | Study Day 2 and 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Samster's triad, Acetylsalicylic acid triad, Widal's triad, Francis' triad, Aspirin triad, Aspirin-induced asthma and rhinitis (AIAR)