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Dose-Response of Inhaled Formoterol
This study has been completed.
First Received: March 20, 2008   Last Updated: February 13, 2009   History of Changes
Sponsors and Collaborators: University of Florida
Teva Global Respiratory Research LLC
Information provided by: University of Florida
ClinicalTrials.gov Identifier: NCT00643578
  Purpose

The purpose of this study is to find out whether a difference between two doses of formoterol can be detected by methacholine challenge.


Condition Intervention
Asthma
Procedure: formoterol

MedlinePlus related topics: Asthma
Drug Information available for: Methacholine Methacholine chloride Formoterol fumarate Arformoterol Formoterol Arformoterol Tartrate
U.S. FDA Resources
Study Type: Interventional
Study Design: Randomized, Open Label, Crossover Assignment, Pharmacodynamics Study
Official Title: A Pilot Study to Evaluate the Dose-Response of Inhaled Formoterol to Inhibit Airway Responsiveness to Methacholine in Patients With Mild Asthma

Further study details as provided by University of Florida:

Primary Outcome Measures:
  • post-dose PC20 [ Time Frame: 3-7 days after visits 1 and 2 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • FEV1 [ Time Frame: 1 hour after dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 10
Study Start Date: March 2008
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
2: Active Comparator
a single dose of 24 mcg of formoterol
Procedure: formoterol
a single dose of 24 mcg of formoterol delivered by dry powder inhaler (Twisthaler)
1: Active Comparator
a single dose of 12 mcg of formoterol
Procedure: formoterol
a single dose of 12 mcg of formoterol delivered by dry powder inhaler (Twisthaler)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00643578

Locations
United States, Florida
University of Florida Asthma Research Lab
Gainesville, Florida, United States, 32610-0486
Sponsors and Collaborators
University of Florida
Teva Global Respiratory Research LLC
Investigators
Principal Investigator: Leslie Hendeles, PharmD University of Florida
  More Information

Publications:
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.
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.
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. Erratum in: J Allergy Clin Immunol. 2006 Apr;117(4):773.
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.
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.
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.
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. No abstract available.
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.
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.

Responsible Party: University of Florida ( Leslie Hendeles, Pharm.D., Professor, Pharmacy and Pediatrics )
Study ID Numbers: Ivax-65307
Study First Received: March 20, 2008
Last Updated: February 13, 2009
ClinicalTrials.gov Identifier: NCT00643578     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Florida:
formoterol
methacholine challenge

Study placed in the following topic categories:
Neurotransmitter Agents
Bronchial Diseases
Adrenergic Agents
Adrenergic beta-Agonists
Miotics
Anti-Asthmatic Agents
Asthma
Cholinergic Agents
Adrenergic Agonists
Lung Diseases, Obstructive
Hypersensitivity
Respiratory Tract Diseases
Lung Diseases
Methacholine Chloride
Hypersensitivity, Immediate
Formoterol
Peripheral Nervous System Agents
Bronchodilator Agents
Respiratory Hypersensitivity

Additional relevant MeSH terms:
Parasympathomimetics
Respiratory System Agents
Neurotransmitter Agents
Cholinergic Agonists
Bronchial Diseases
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Bronchoconstrictor Agents
Physiological Effects of Drugs
Cholinergic Agents
Adrenergic Agonists
Hypersensitivity
Lung Diseases, Obstructive
Respiratory Tract Diseases
Therapeutic Uses
Formoterol
Adrenergic beta-Agonists
Immune System Diseases
Miotics
Asthma
Anti-Asthmatic Agents
Pharmacologic Actions
Autonomic Agents
Lung Diseases
Methacholine Chloride
Muscarinic Agonists
Hypersensitivity, Immediate
Peripheral Nervous System Agents
Bronchodilator Agents
Respiratory Hypersensitivity

ClinicalTrials.gov processed this record on May 07, 2009