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Dose-response of Inhaled Formoterol Using Methacholine Challenge as a Bioassay

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00643578
First Posted: March 26, 2008
Last Update Posted: December 5, 2011
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Teva Branded Pharmaceutical Products, R&D Inc.
Information provided by (Responsible Party):
University of Florida
  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 Drug: formoterol Device: Dry Powder Inhaler (Twisthaler)

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Official Title: A Pilot Study to Evaluate the Dose-response of Inhaled Formoterol to Inhibit Airway Responsiveness to Methacholine in Patients With Mild Asthma

Resource links provided by NLM:


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 ]
    The PC20 is the provocational dose of methacholine causing a 20% drop in forced expiratory volume in the first second.


Secondary Outcome Measures:
  • FEV1 [ Time Frame: 1 hour after dose ]
    The forced expiratory volume in the first second, expressed as a percent predicted.


Enrollment: 37
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
Active Comparator: 2
a single dose of 24 mcg of formoterol
Drug: formoterol
a single dose of 24 mcg of formoterol delivered by dry powder inhaler (Twisthaler)
Device: Dry Powder Inhaler (Twisthaler)
subjects inhaled deeply and forcefully and held their breath for 10 seconds for each dose
Active Comparator: 1
a single dose of 12 mcg of formoterol
Drug: formoterol
a single dose of 12 mcg of formoterol delivered by dry powder inhaler (Twisthaler)
Device: Dry Powder Inhaler (Twisthaler)
subjects inhaled deeply and forcefully and held their breath for 10 seconds for each dose

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

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00643578


Locations
United States, Florida
University of Florida Asthma Research Lab
Gainesville, Florida, United States, 32610-0486
Sponsors and Collaborators
University of Florida
Teva Branded Pharmaceutical Products, R&D Inc.
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.
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
ClinicalTrials.gov Identifier: NCT00643578     History of Changes
Other Study ID Numbers: Ivax-65307
First Submitted: March 20, 2008
First Posted: March 26, 2008
Results First Submitted: August 5, 2011
Results First Posted: November 18, 2011
Last Update Posted: December 5, 2011
Last Verified: November 2011

Keywords provided by University of Florida:
formoterol
methacholine challenge

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Formoterol Fumarate
Methacholine Chloride
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Miotics
Parasympathomimetics
Bronchoconstrictor Agents
Muscarinic Agonists
Cholinergic Agonists
Cholinergic Agents


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