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| Name | Class |
|---|---|
| Teva Branded Pharmaceutical Products R&D, Inc. | INDUSTRY |
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The purpose of this study is to find out whether a difference between two doses of formoterol can be detected by methacholine challenge.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 2 | Active Comparator | a single dose of 24 mcg of formoterol |
|
| 1 | Active Comparator | a single dose of 12 mcg of formoterol |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| formoterol | Drug | a single dose of 24 mcg of formoterol delivered by dry powder inhaler (Twisthaler) |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Post-dose PC20 | The PC20 is the provocational dose of methacholine causing a 20% drop in forced expiratory volume in the first second. | 3-7 days after visits 1 and 2 |
| Measure | Description | Time Frame |
|---|---|---|
| FEV1 | The forced expiratory volume in the first second, expressed as a percent predicted. | 1 hour after dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Leslie Hendeles, PharmD | University of Florida | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Florida Asthma Research Lab | Gainesville | Florida | 32610-0486 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 3294976 | Background | Ahrens RC, Harris JB, Milavetz G, Annis L, Ries R. Use of bronchial provocation with histamine to compare the pharmacodynamics of inhaled albuterol and metaproterenol in patients with asthma. J Allergy Clin Immunol. 1987 Jun;79(6):876-82. doi: 10.1016/0091-6749(87)90235-1. | |
| 1310456 | Background | Blake KV, Hoppe M, Harman E, Hendeles L. Relative amount of albuterol delivered to lung receptors from a metered-dose inhaler and nebulizer solution. Bioassay by histamine bronchoprovocation. Chest. 1992 Feb;101(2):309-15. doi: 10.1378/chest.101.2.309. |
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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.
Between April and November, 2008, the UF Asthma Research Lab recruited 37 patients for study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Formoterol 12 First | a single dose of 12 mcg of formoterol was given first, then 24 mcg of formoterol |
| FG001 | Formoterol 24 First | a single dose of 24 mcg of formoterol was given first, then 12 mcg of formoterol |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | All Participants | A single dose of 12 mcg and 24 mcg, on separate days, of formoterol were given. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Post-dose PC20 | The PC20 is the provocational dose of methacholine causing a 20% drop in forced expiratory volume in the first second. | 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. | Posted | Geometric Mean | 95% Confidence Interval | mg/mL | 3-7 days after visits 1 and 2 |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Formoterol 12 | A single dose of 12 mcg of formoterol was administered. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Leslie Hendeles | University of Florida Asthma Research Lab | 352-273-6027 | hendeles@cop.ufl.edu |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D000068759 | Formoterol Fumarate |
| D058995 | Dry Powder Inhalers |
| ID | Term |
|---|---|
| D004983 | Ethanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
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| formoterol |
| Drug |
a single dose of 12 mcg of formoterol delivered by dry powder inhaler (Twisthaler) |
|
| Dry Powder Inhaler (Twisthaler) | Device | subjects inhaled deeply and forcefully and held their breath for 10 seconds for each dose |
|
| 15208585 | Background | Hendeles L, Beaty R, Ahrens R, Stevens G, Harman EM. Response to inhaled albuterol during nocturnal asthma. J Allergy Clin Immunol. 2004 Jun;113(6):1058-62. doi: 10.1016/j.jaci.2004.03.046. |
| 10390425 | Background | Parameswaran KN, Inman MD, Ekholm BP, Morris MM, Summers E, O'Byrne PM, Hargreave FE. Protection against methacholine bronchoconstriction to assess relative potency of inhaled beta2-agonist. Am J Respir Crit Care Med. 1999 Jul;160(1):354-7. doi: 10.1164/ajrccm.160.1.9812035. |
| 10508813 | Background | Ahrens RC, Hendeles L, Clarke WR, Dockhorn RJ, Hill MR, Vaughan LM, Lux C, Han SH. Therapeutic equivalence of Spiros dry powder inhaler and Ventolin metered dose inhaler. A bioassay using methacholine. Am J Respir Crit Care Med. 1999 Oct;160(4):1238-43. doi: 10.1164/ajrccm.160.4.9806101. |
| 12417879 | Background | Creticos PS, Adams WP, Petty BG, Lewis LD, Singh GJ, Khattignavong AP, Molzon JA, Martinez MN, Lietman PS, Williams RL. A methacholine challenge dose-response study for development of a pharmacodynamic bioequivalence methodology for albuterol metered- dose inhalers. J Allergy Clin Immunol. 2002 Nov;110(5):713-20. doi: 10.1067/mai.2002.129036. |
| 16055882 | Background | Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available. |
| 9872837 | Background | Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999 Jan;159(1):179-87. doi: 10.1164/ajrccm.159.1.9712108. |
| 12006455 | Background | Asmus MJ, Vaughan LM, Hill MR, Chesrown SE, Hendeles L. Stability of frozen methacholine solutions in unit-dose syringes for bronchoprovocation. Chest. 2002 May;121(5):1634-7. doi: 10.1378/chest.121.5.1634. |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | FEV1 | The forced expiratory volume in the first second, expressed as a percent predicted. | 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. | Posted | Mean | Standard Deviation | percent predicted | 1 hour after dose |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | Formoterol 24 | A single dose of 24 mcg of formoterol was administered. | 0 | 10 | 0 | 10 |
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| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D000588 |
| Amines |
| D009330 | Nebulizers and Vaporizers |
| D004864 | Equipment and Supplies |