Evaluation of the Effect of Levalbuterol on Allergen Induced Airway Inflammation In Subjects With Atopic Asthma - Full Text View

Sponsor:	Hamilton Health Sciences Corporation
Collaborator:	Sunovion
Information provided by:	McMaster University
ClinicalTrials.gov Identifier:	NCT00320034

Purpose

The most commonly used drug for immediate relief of symptoms of asthma is the blue puffer, albuterol or salbutamol (Ventolin). Racemic albuterol is a mixture of two forms of albuterol which are mirror images of each other i.e. R-and S- isomers. The investigational treatments are R-albuterol and S-albuterol.

R-albuterol ( levalbuterol) has been shown to have a slightly better bronchodilator effect as compared to the racemic albuterol and is well- tolerated in patients. However it is still not clear whether the S-isomer has no effect or has a harmful effect on the airways.

The purpose of this study is to compare the effects of the R- and S- isomers on allergen induced airway inflammation in subjects with mild atopic asthma. This will give us a better idea as to whether the routine use of levalbuterol is superior to racemic albuterol.

Condition	Intervention	Phase
Asthma	Drug: R-albuterol, S-albuterol	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Crossover Assignment Masking: Double-Blind Primary Purpose: Treatment
Official Title:	Double-blind, Crossover, Placebo-controlled Evaluation of the Effect of Levalbuterol (R-albuterol) on Allergen Induced Airway Inflammation In Subjects With Atopic Asthma

Resource links provided by NLM:

MedlinePlus related topics: Asthma

Drug Information available for: Albuterol Levalbuterol hydrochloride Albuterol sulfate Levalbuterol tartrate

U.S. FDA Resources

Further study details as provided by McMaster University:

Primary Outcome Measures:

The change in airway eosinophil number (% and absolute numbers) following an allergen inhalation.

Secondary Outcome Measures:

Changes in:
PC20 methacholine
Allergen-induced early and late asthma responses
Airway eosinophil activation (EG-2+ eosinophils)
Levels of IL-5, RANTES, and eotaxin in sputum
Expression of PLCß1 on airway eosinophils

Estimated Enrollment:	15
Study Start Date:	April 2006
Study Completion Date:	November 2009
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Detailed Description:

The most commonly used drug for immediate relief of symptoms of asthma is the blue puffer, albuterol or salbutamol (Ventolin). Racemic albuterol is a mixture of two forms of albuterol which are mirror images of each other i.e. R-and S- isomers. The investigational treatments are R-albuterol and S-albuterol .

R-albuterol ( levalbuterol) relieves the narrowing of the bronchial air passages in the lungs and has been approved by the U.S. FDA, but is not currently licensed for use in Canada. We have obtained approval from Health Canada to use these isomers for the purpose of this study. R-albuterol has been shown to have a slightly better bronchodilator effect as compared to the racemic albuterol and is well- tolerated in patients, with only a few mild to moderate side effects (such as palpitations, diarrhoea, abdominal pain, bodyache, leg cramps and headache). However it is still not clear whether the S-isomer has no effect or has a harmful effect on the airways.

The purpose of this study is to determine the effect of this drug, levalbuterol, on the allergen-induced inflammatory response in adult subjects with asthma. Specifically, we want to look for changes in airway eosinophils by examining sputum samples and to compare the effects of the R- and S- isomers on airway inflammation. This will help us to understand whether the racemic albuterol could worsen inflammation because of the presence of the S-isomer, and this will give us a better idea as to whether the routine use of levalbuterol is superior to racemic albuterol.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Male or female (medically or surgically postmenopausal or practicing an accepted form of barrier or hormonal contraception) subjects age 18-55.
Stable, mild atopic asthma with forced expiratory volume in one second (FEV1.0) greater than 70% of predicted for age and height, and not requiring any medical treatment other than short acting inhaled beta-agonists as needed.
No recent or significant history of cigarette smoking (no cigarettes within six months prior to entry into the study; less than 10 pack-years cumulative history of cigarette smoking).
Peak decrease in FEV1 in both early (0-2 hour) and late (3-7 hour) allergen-provoked response of > 15% compared with the baseline (pre-allergen challenge) spirometric determination.
Signed written informed consent to participate in the protocol; ability to return to the outpatient clinic for repeated clinic visits.
No history of asthma exacerbations or acute intercurrent respiratory illness (viral respiratory syndrome, bronchitis, pneumonia) for a six week period preceding entry into the screening phase of the study.

Exclusion Criteria:

Significant gastrointestinal (including hepatic), hematological, cardiovascular, cerebrovascular or other body system disorder.
History of an acute exacerbation, or of a respiratory tract infection at any time during the past 6 weeks.
Baseline AST or ALT (indicators of liver damage) greater than twice the upper limit of the normal range for the local laboratory.
History of allergy or hypersensitivity to short-acting beta-agonists.
Inability to discontinue asthma medications for the duration of the study or receipt of oral or inhaled corticosteroids or leukotriene receptor antagonist in the three weeks prior to entry into the screening phase of the study.
Recent (within the past 2 months) or planned (within the study period) lung volume reduction surgery.
Psychosis, alcoholism, active substance abuse, or any personality disorder which would make compliance with this protocol problematic.
Pregnant or nursing females.
Any other medical or social condition which, in the opinion of the investigator, could confound the interpretation of the data derived from this study.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00320034

Sponsors and Collaborators

Hamilton Health Sciences Corporation

Sunovion

Investigators

Principal Investigator:

Parameswaran Nair, MD

Firestone Institute for Respiratory Health, St. Joseph's Healthcare

More Information

Publications:

Lotvall J, Palmqvist M, Arvidsson P, Maloney A, Ventresca GP, Ward J. The therapeutic ratio of R-albuterol is comparable with that of RS-albuterol in asthmatic patients. J Allergy Clin Immunol. 2001 Nov;108(5):726-31.

Handley DA, Tinkelman D, Noonan M, Rollins TE, Snider ME, Caron J. Dose-response evaluation of levalbuterol versus racemic albuterol in patients with asthma. J Asthma. 2000 Jun;37(4):319-27.

ClinicalTrials.gov Identifier:	NCT00320034 History of Changes
Other Study ID Numbers:	SRC 192
Study First Received:	April 27, 2006
Last Updated:	February 28, 2011
Health Authority:	Canada: Health Canada

Keywords provided by McMaster University:

levalbuterol
asthma
allergen provocation
airway inflammation
clinical trial

Additional relevant MeSH terms:

Asthma
Inflammation
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Pathologic Processes
Albuterol
Tocolytic Agents
Reproductive Control Agents

Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents

ClinicalTrials.gov processed this record on February 12, 2012