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

NCT00643578 | Completed Results

• 1 other identifier: Ivax-65307
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Keywords

formoterol; methacholine challenge

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• FEV1

  1 hour after dose

Study Arms (2)

2

ACTIVE COMPARATOR

a single dose of 24 mcg of formoterol

Drug: formoterol; Device: Dry Powder Inhaler (Twisthaler)

1

ACTIVE COMPARATOR

a single dose of 12 mcg of formoterol

Drug: formoterol; Device: Dry Powder Inhaler (Twisthaler)

Interventions

formoterol DRUG

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

2

Dry Powder Inhaler (Twisthaler) DEVICE

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

1; 2

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Florida: lead
• Teva Branded Pharmaceutical Products R&D, Inc.: collaborator

Study Sites (1)

University of Florida Asthma Research Lab

Gainesville, Florida, 32610-0486, United States

Location

Related Publications (9)

• 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.

  PMID: 3294976 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.

  PMID: 1310456 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.

  PMID: 15208585 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.

  PMID: 10390425 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.

  PMID: 10508813 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.

  PMID: 12417879 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.

  PMID: 16055882 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.

  PMID: 9872837 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.

  PMID: 12006455 BACKGROUND

MeSH Terms

Conditions

Asthma

Interventions

Formoterol Fumarate; Dry Powder Inhalers

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Nebulizers and Vaporizers; Equipment and Supplies

Results Point of Contact

• Title: Dr. Leslie Hendeles
• Organization: University of Florida Asthma Research Lab

hendeles@cop.ufl.edu

352-273-6027

Study Officials

• Leslie Hendeles, PharmD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2008
• First Posted: March 26, 2008
• Study Start: March 1, 2008
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: December 5, 2011
• Results First Posted: November 18, 2011

Record last verified: 2011-11

Locations

US (1)