Aspirin Exacerbated Respiratory Disease (AERD)
Conditions
Keywords
Samster's triad, Acetylsalicylic acid triad, Widal's triad, Francis' triad, Aspirin triad, Aspirin-induced asthma and rhinitis (AIAR)
Brief 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.
Interventions
DRUGIfetroban, Oral Capsule
DRUGPlacebo, Oral Capsule
Sponsors
Cumberland Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame | Description |
|---|---|---|
| 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% 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 | — |
| Amount of Rescue Medication Required During the Aspirin Challenge | Study Day 2 and 3 | The amount of rescue medication required during the aspirin challenge |
| 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 | — |
| Proportion of Patients With a ≥ 25% Increase in TNSS Compared to Baseline During the Aspirin Challenge | Study Day 2 and 3 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ifetroban, Oral Capsule Ifetroban, Oral Capsule; 200 mg per dose (four - 50 mg capsules), once per day on Study Days 1, 2, and 3.
Ifetroban, Oral Capsule | 12 |
| Placebo, Oral Capsule Placebo, Oral Capsule; matching capsules for oral ifetroban dosing, four capsules once per day on Study Days 1, 2, and 3.
Placebo, Oral Capsule | 4 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Inclusion or exclusion criteria not met | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Ifetroban, Oral Capsule | Placebo, Oral Capsule |
|---|---|---|---|
| Age, Continuous | 45 years STANDARD_DEVIATION 11.7 | 46 years STANDARD_DEVIATION 11.6 | 43 years STANDARD_DEVIATION 13.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 10 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 9 Participants | 4 Participants |
| Region of Enrollment United States | 16 Participants | 12 Participants | 4 Participants |
| Sex: Female, Male Female | 8 Participants | 6 Participants | 2 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 4 |
| other Total, other adverse events | 11 / 12 | 4 / 4 |
| serious Total, serious adverse events | 0 / 12 | 0 / 4 |
Outcome results
Primary
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
Time frame: Study Day 2
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ifetroban, Oral Capsule | 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 | 0 Participants |
| Placebo, Oral Capsule | 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 | 0 Participants |
Secondary
Amount of Rescue Medication Required During the Aspirin Challenge
The amount of rescue medication required during the aspirin challenge
Time frame: Study Day 2 and 3
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ifetroban, Oral Capsule | Amount of Rescue Medication Required During the Aspirin Challenge | 2.9 number of rescue medications | Standard Deviation 2.02 |
| Placebo, Oral Capsule | Amount of Rescue Medication Required During the Aspirin Challenge | 7.33 number of rescue medications | Standard Deviation 3.79 |
Secondary
Incidence and Severity of Asthmatic Reactions During the Treatment Period
Time frame: Study Day 1 through 3
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ifetroban, Oral Capsule | Incidence and Severity of Asthmatic Reactions During the Treatment Period | 0 Participants |
| Placebo, Oral Capsule | Incidence and Severity of Asthmatic Reactions During the Treatment Period | 0 Participants |
Secondary
Incidence and Severity of Treatment-emergent Adverse Events
Time frame: Up to Study Day 7
Population: Number of subject reporting at least one adverse event
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ifetroban, Oral Capsule | Incidence and Severity of Treatment-emergent Adverse Events | 11 Participants |
| Placebo, Oral Capsule | Incidence and Severity of Treatment-emergent Adverse Events | 4 Participants |
Secondary
Proportion of Patients Who Experience a ≥ 20% Decrease in FEV1 Compared to Baseline During the Aspirin Challenge
Time frame: Study Day 2 and 3
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ifetroban, Oral Capsule | Proportion of Patients Who Experience a ≥ 20% Decrease in FEV1 Compared to Baseline During the Aspirin Challenge | 0 Participants |
| Placebo, Oral Capsule | Proportion of Patients Who Experience a ≥ 20% Decrease in FEV1 Compared to Baseline During the Aspirin Challenge | 0 Participants |
Secondary
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
Time frame: Up to Study Day 2
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ifetroban, Oral Capsule | 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 | 2 Participants |
| Placebo, Oral Capsule | 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 | 1 Participants |
Secondary
Proportion of Patients With a ≥ 25% Decrease in Peak Nasal Inspiratory Flow Rate (NIFR) Compared to Baseline During the Aspirin Challenge
Time frame: Study Day 2 and 3
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ifetroban, Oral Capsule | Proportion of Patients With a ≥ 25% Decrease in Peak Nasal Inspiratory Flow Rate (NIFR) Compared to Baseline During the Aspirin Challenge | 4 Participants |
| Placebo, Oral Capsule | Proportion of Patients With a ≥ 25% Decrease in Peak Nasal Inspiratory Flow Rate (NIFR) Compared to Baseline During the Aspirin Challenge | 1 Participants |
Secondary
Proportion of Patients With a ≥ 25% Increase in TNSS Compared to Baseline During the Aspirin Challenge
Time frame: Study Day 2 and 3
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ifetroban, Oral Capsule | Proportion of Patients With a ≥ 25% Increase in TNSS Compared to Baseline During the Aspirin Challenge | 3 Participants |
| Placebo, Oral Capsule | Proportion of Patients With a ≥ 25% Increase in TNSS Compared to Baseline During the Aspirin Challenge | 1 Participants |
Secondary
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
Time frame: Up to Study Day 2
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ifetroban, Oral Capsule | 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 | 0 Participants |
| Placebo, Oral Capsule | 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 | 0 Participants |
Secondary
Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg.
Time frame: Study Day 2 and 3
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ifetroban, Oral Capsule | Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg. | 30 mg aspirin dose | 0 Participants |
| Ifetroban, Oral Capsule | Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg. | 60 mg aspirin dose | 5 Participants |
| Ifetroban, Oral Capsule | Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg. | 100mg aspirin dose | 5 Participants |
| Ifetroban, Oral Capsule | Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg. | 150 mg aspirin dose | 0 Participants |
| Ifetroban, Oral Capsule | Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg. | 325 mg aspirin dose | 0 Participants |
| Ifetroban, Oral Capsule | Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg. | No Aspirin Reaction | 2 Participants |
| Placebo, Oral Capsule | Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg. | 325 mg aspirin dose | 0 Participants |
| Placebo, Oral Capsule | Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg. | 30 mg aspirin dose | 0 Participants |
| Placebo, Oral Capsule | Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg. | 150 mg aspirin dose | 0 Participants |
| Placebo, Oral Capsule | Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg. | 60 mg aspirin dose | 2 Participants |
| Placebo, Oral Capsule | Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg. | No Aspirin Reaction | 1 Participants |
| Placebo, Oral Capsule | Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg. | 100mg aspirin dose | 1 Participants |