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

NCT ID: NCT00643578

Last Updated: 2011-12-05

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

37 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-03-31

Study Completion Date

2009-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Asthma

Keywords

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formoterol methacholine challenge

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Blinding Strategy

NONE

Study Groups

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2

a single dose of 24 mcg of formoterol

Group Type ACTIVE_COMPARATOR

formoterol

Intervention Type DRUG

a single dose of 24 mcg of formoterol delivered by dry powder inhaler (Twisthaler)

Dry Powder Inhaler (Twisthaler)

Intervention Type DEVICE

subjects inhaled deeply and forcefully and held their breath for 10 seconds for each dose

1

a single dose of 12 mcg of formoterol

Group Type ACTIVE_COMPARATOR

formoterol

Intervention Type DRUG

a single dose of 12 mcg of formoterol delivered by dry powder inhaler (Twisthaler)

Dry Powder Inhaler (Twisthaler)

Intervention Type DEVICE

subjects inhaled deeply and forcefully and held their breath for 10 seconds for each dose

Interventions

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formoterol

a single dose of 24 mcg of formoterol delivered by dry powder inhaler (Twisthaler)

Intervention Type DRUG

formoterol

a single dose of 12 mcg of formoterol delivered by dry powder inhaler (Twisthaler)

Intervention Type DRUG

Dry Powder Inhaler (Twisthaler)

subjects inhaled deeply and forcefully and held their breath for 10 seconds for each dose

Intervention Type DEVICE

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Teva Branded Pharmaceutical Products R&D, Inc.

INDUSTRY

Sponsor Role collaborator

University of Florida

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Leslie Hendeles, PharmD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

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University of Florida Asthma Research Lab

Gainesville, Florida, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 3294976 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 1310456 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15208585 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10390425 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10508813 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12417879 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16055882 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9872837 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12006455 (View on PubMed)

Other Identifiers

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Ivax-65307

Identifier Type: -

Identifier Source: org_study_id