Asthma
Conditions
Keywords
formoterol, methacholine challenge
Brief summary
The purpose of this study is to find out whether a difference between two doses of formoterol can be detected by methacholine challenge.
Detailed description
During the screening visit, subjects'vital signs (heart rate, blood pressure and temperature) will be measured and they will perform standard spirometry. If the results of this test are 70% of normal or greater, they will be examined by a physician, and blood (1 teaspoonful) and urine will be collected for routine laboratory tests (CBC and routine urinalysis). If they are a female, a pregnancy test will be performed. During the second visit, subjects will inhale 1 or 2 doses of formoterol, (Foradil Aerolizer 12 mcg/capsule) a long-acting bronchodilator and 1 hour later, perform a methacholine test. At the end of the methacholine test, they will be given albuterol to reverse the effects of methacholine. On the third study day, they will repeat the second visit but with the opposite dose of Foradil.
Interventions
DRUGformoterol
a single dose of 24 mcg of formoterol delivered by dry powder inhaler (Twisthaler)
DEVICEDry Powder Inhaler (Twisthaler)
subjects inhaled deeply and forcefully and held their breath for 10 seconds for each dose
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
University of Florida
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Non-smoking male or female 18 60 years of age, with a previous diagnosis of asthma that has been stable for at least 4 weeks and which is unlikely to exacerbate during the study because of, for example, seasonal allergen exposure. Women of childbearing age must not be pregnant or nursing, and must be using an acceptable method of contraception. * Ability to perform ATS/ERS-acceptable and reproducible spirometry7 * Screening FEV1 ≥70% of predicted for height, age, sex, and race when short-acting inhaled bronchodilators are withheld for at least 6 hours * At least a 20% decrease in FEV1 after inhaling ≤4 mg/mL of methacholine (i.e., a PC20 FEV1 ≤4 mg/mL) * Can be taught to use the dry powder device in accordance with the product's medication guide. * If using an oral inhaled or intranasal corticosteroid, dosage must be stable for at least 4 weeks.
Exclusion criteria
* Allergy or sensitivity to inhaled methacholine, formoterol or to other β2 agonists * Intolerance to other components of the inhaler or sensitivity to milk proteins * Cigarette smoking in past year or \>10 pack-year smoking history * Respiratory tract infection within the last four weeks * History of severe asthma attack requiring hospitalization in the previous 12 months * Short course of oral and/or systemic corticosteroids in the past 4 weeks * Inability to withhold caffeinated beverages for 12 hours or medications for appropriate intervals prior to each methacholine challenge * Require treatment with beta-blockers (administered by any route), MAO inhibitors, tricyclic antidepressants, and/or maintenance therapy with systemic corticosteroids * History and/or presence of pulmonary conditions (including but not limited to cystic fibrosis and bronchiectasis) other than asthma * History of clinically-significant cardiovascular, renal, neurologic, liver or endocrine dysfunction. Patients with well-controlled hypertension, hypercholesterolemia or diabetes will not be excluded. * If female, a positive urine β-HCG test * Known or suspected substance abuse (e.g., alcohol, marijuana, etc.) and/or any other medical or psychological conditions that in the investigator's opinion should preclude study enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-dose PC20 | 3-7 days after visits 1 and 2 | The PC20 is the provocational dose of methacholine causing a 20% drop in forced expiratory volume in the first second. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| FEV1 | 1 hour after dose | The forced expiratory volume in the first second, expressed as a percent predicted. |
Countries
United States
Participant flow
Recruitment details
Between April and November, 2008, the UF Asthma Research Lab recruited 37 patients for study.
Pre-assignment details
Of the 37 subjects who signed informed consent, 25 did not meet inclusion/exclusion criteria. The provocational dose of methacholine causing a 20% drop in forced expiratory volume in the first second (PC20FEV1) was not less than or equal to 4 mg/mL.
Participants by arm
| Arm | Count |
|---|---|
| All Participants A single dose of 12 mcg and 24 mcg, on separate days, of formoterol were given. | 12 |
| Total | 12 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Age Continuous | 36.8 years STANDARD_DEVIATION 14.5 |
| Region of Enrollment United States | 12 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
Post-dose PC20
The PC20 is the provocational dose of methacholine causing a 20% drop in forced expiratory volume in the first second.
Time frame: 3-7 days after visits 1 and 2
Population: Of the 12 subjects who qualified for randomization, 2 had a PC20 greater than 128 mg/mL (the maximum concentration of methacholine administered), after receiving 12 mcg of formoterol. Therefore, they were discontinued from the study since their PC20 would not be measurable with a higher dose of formoterol.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| 12 Mcg Formoterol | Post-dose PC20 | 7 mg/mL |
| 24 Mcg Formoterol | Post-dose PC20 | 16 mg/mL |
Secondary
FEV1
The forced expiratory volume in the first second, expressed as a percent predicted.
Time frame: 1 hour after dose
Population: Of the 12 subjects who qualified for randomization, 2 had a PC20 greater than 128 mg/mL (the maximum concentration of methacholine administered), after receiving 12 mcg of formoterol. Therefore, they were discontinued from the study since their PC20 would not be measurable with a higher dose of formoterol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 12 Mcg Formoterol | FEV1 | 88 percent predicted | Standard Deviation 12 |
| 24 Mcg Formoterol | FEV1 | 91 percent predicted | Standard Deviation 10 |