Clinical trial NCT00940927: Dose-response of Albuterol in Asthmatics
Official title: Exclusion of Asthmatics From Clinical Trials Due to the 15 Percent Rule
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Keywords: Albuterol
Forced expiratory volume in one second
Dose at fifty percent of maximum effect
Maximum effective dose
Metered dose inhaler
Nebulizer
Lead sponsor: Nemours Children's Clinic
Sponsor class: OTHER
First posted: 2009-07-17
Enrollment: 81
Sex: ALL
Minimum age (years): 8
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to determine the lung function response after increasing doses of albuterol (a bronchodilator) in children and adults with asthma.

Detailed description: Inhaled short-acting b2-agonists (SABA) are the most potent bronchodilators used today to treat acute symptoms of asthma and albuterol, a partial b2-agonist, is the most frequently prescribed asthma medication in the US. Although universally used in for acute asthma symptoms, SABA have been associated with a significant degree of interpatient variability. Many studies have characterized the SABA dose to bronchodilator response relationship under controlled conditions. However, few studies have explored the magnitude and sources of bronchodilator response variability, and no studies have characterized the dose versus bronchodilator response relationship using population pharmacokinetic/pharmacodynamic (PPK/PD) modeling. In the present study, we characterized the relationship between inhaled doses of albuterol and bronchodilation in 81 children and adults with moderate to severe persistent asthma using a population pharmacodynamic approach. The purpose of this study was to obtain estimates of the pharmacodynamic parameters that characterize the dose-response curve, including maximal dose for bronchodilation, and to quantify and identify sources of interpatient pharmacodynamic variability.

Eligibility criteria: Eligibility Criteria:

* Well-defined history of physician diagnosed asthma
* Any ethnic background
* 8 to 65 years old
* Baseline pre-bronchodilator FEV1 of 40% to 80% predicted for age, height, and gender
* No oral corticosteroid use, emergency room visits, or hospitalizations within the previous 3 months
* Nonsmokers or less than a 5 pack-year history with no smoking in the previous year
* Normal physical exam and no confounding diseases were selected
* Able to withhold inhaled short-acting b2-agonists or inhaled anticholinergic drugs for 8 hours, oral antihistamines for 5 days, theophylline for 24 hours, and cromolyn, nedocromil, and inhaled corticosteroids for 2 hours prior to the study.

Primary outcomes:
measure: Effective Dose 50% (ED50)
timeFrame: 15 minutes after each dose
measure: Effect Maximum (Emax)
timeFrame: 15 minutes after each dose
Secondary outcomes:
Other outcomes:
Locations:
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
Study officials:
affiliation: Nemours Children's Clinic
name: Kathryn V Blake, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Blake K, Madabushi R, Derendorf H, Lima J. Population pharmacodynamic model of bronchodilator response to inhaled albuterol in children and adults with asthma. Chest. 2008 Nov;134(5):981-989. doi: 10.1378/chest.07-2991. Epub 2008 Jun 26.