Dose-response of Albuterol in Asthmatics

Asthma Clinical Trial

Official title:

Exclusion of Asthmatics From Clinical Trials Due to the 15 Percent Rule

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00940927
• Other study ID #: 93-41
• Status: Completed
• Phase: Phase 4
• First received: June 27, 2008
• Last updated: April 14, 2015
• Start date: July 1993
• Est. completion date: October 1994

Study information

• Verified date: April 2015
• Source: Nemours Children's Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 81
• Est. completion date: October 1994
• Est. primary completion date: October 1994
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 8 Years to 65 Years

Eligibility

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.

Study Design

Endpoint Classification: Pharmacodynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• albuterol
Albuterol administered sequentially 180mcg (MDI), 90mcg (MDI), 90mcg(MDI), 90mcg (MDI), 90mcg (MDI), 2.5mg (nebulized)

Locations

Country	Name	City	State
United States	Nemours Children's Clinic	Jacksonville	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Nemours Children's Clinic

Country where clinical trial is conducted

United States, 

References & Publications (1)

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):981-9. doi: 10.1378/chest.07-2991. Epub 2008 Jun 26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effective Dose 50% (ED50)	ED50 is the cumulative dose of albuterol required to bring about 50% of maximum effect of albuterol	15 minutes after each dose	No
Primary	Effect Maximum (Emax)	Maximum percentage of predicted FEV1 effect	15 minutes after each dose	No