Trial to Determine the Safety of Oral Ifetroban in Patients With a History of Aspirin Exacerbated Respiratory Disease
Primary Purpose
Aspirin Exacerbated Respiratory Disease (AERD)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ifetroban, Oral Capsule
Placebo, Oral Capsule
Sponsored by
![Cumberland Pharmaceuticals](https://trials-media.s3.amazonaws.com/orgs/cumberland-pharmaceuticals.jpeg)
About this trial
This is an interventional treatment trial for Aspirin Exacerbated Respiratory Disease (AERD) focused on measuring Samster's triad, Acetylsalicylic acid triad, Widal's triad, Francis' triad, Aspirin triad, Aspirin-induced asthma and rhinitis (AIAR)
Eligibility Criteria
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.
Sites / Locations
- Scripps Clinic
- Kansas City Allergy and Asthma Associates, PA.
- Allergy & Asthma Consultants of Rockland & Bergen
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Ifetroban, Oral Capsule
Placebo, Oral Capsule
Arm Description
Ifetroban, Oral Capsule; 200 mg per dose (four - 50 mg capsules), once per day on Study Days 1, 2, and 3.
Placebo, Oral Capsule; matching capsules for oral ifetroban dosing, four capsules once per day on Study Days 1, 2, and 3.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
Incidence and Severity of Treatment-emergent Adverse Events
Proportion of Patients Who Experience a ≥ 20% Decrease in FEV1 Compared to Baseline During the Aspirin Challenge
Proportion of Patients With a ≥ 25% Decrease in Peak Nasal Inspiratory Flow Rate (NIFR) Compared to Baseline During the Aspirin Challenge
Proportion of Patients With a ≥ 25% Increase in TNSS Compared to Baseline During the Aspirin Challenge
Amount of Rescue Medication Required During the Aspirin Challenge
The amount of rescue medication required during the aspirin challenge
Incidence and Severity of Asthmatic Reactions During the Treatment Period
Proportion of Patients With an Aspirin Desensitization Dose Level of 30 mg, 60 mg, 100 mg, 150 mg, and 325 mg.
Full Information
NCT ID
NCT02216357
First Posted
August 12, 2014
Last Updated
April 9, 2017
Sponsor
Cumberland Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02216357
Brief Title
Trial to Determine the Safety of Oral Ifetroban in Patients With a History of Aspirin Exacerbated Respiratory Disease
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
August 2014 (undefined)
Primary Completion Date
January 2016 (Actual)
Study Completion Date
January 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cumberland Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aspirin Exacerbated Respiratory Disease (AERD)
Keywords
Samster's triad, Acetylsalicylic acid triad, Widal's triad, Francis' triad, Aspirin triad, Aspirin-induced asthma and rhinitis (AIAR)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Ifetroban, Oral Capsule
Arm Type
Active Comparator
Arm Description
Ifetroban, Oral Capsule; 200 mg per dose (four - 50 mg capsules), once per day on Study Days 1, 2, and 3.
Arm Title
Placebo, Oral Capsule
Arm Type
Placebo Comparator
Arm Description
Placebo, Oral Capsule; matching capsules for oral ifetroban dosing, four capsules once per day on Study Days 1, 2, and 3.
Intervention Type
Drug
Intervention Name(s)
Ifetroban, Oral Capsule
Intervention Type
Drug
Intervention Name(s)
Placebo, Oral Capsule
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
Title
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
Title
Incidence and Severity of Treatment-emergent Adverse Events
Time Frame
Up to Study Day 7
Title
Proportion of Patients Who Experience a ≥ 20% Decrease in FEV1 Compared to Baseline During the Aspirin Challenge
Time Frame
Study Day 2 and 3
Title
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
Title
Proportion of Patients With a ≥ 25% Increase in TNSS Compared to Baseline During the Aspirin Challenge
Time Frame
Study Day 2 and 3
Title
Amount of Rescue Medication Required During the Aspirin Challenge
Description
The amount of rescue medication required during the aspirin challenge
Time Frame
Study Day 2 and 3
Title
Incidence and Severity of Asthmatic Reactions During the Treatment Period
Time Frame
Study Day 1 through 3
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
Scripps Clinic
City
San Diego
State/Province
California
ZIP/Postal Code
32130
Country
United States
Facility Name
Kansas City Allergy and Asthma Associates, PA.
City
Overland Park
State/Province
Kansas
ZIP/Postal Code
66210
Country
United States
Facility Name
Allergy & Asthma Consultants of Rockland & Bergen
City
West Nyack
State/Province
New York
ZIP/Postal Code
10994
Country
United States
12. IPD Sharing Statement
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Trial to Determine the Safety of Oral Ifetroban in Patients With a History of Aspirin Exacerbated Respiratory Disease
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