Dose-response of Albuterol in Asthmatics

• Sponsor: Nemours Children's Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT00940927
• Collaborator: (none)
• Enrollment: 81
• Location: 1
• Duration (Months): 15
• Patients Per Site Per Month: 5.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: albuterol	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 81 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Exclusion of Asthmatics From Clinical Trials Due to the 15 Percent Rule
• Study Start Date: Jul 1, 1993
• Actual Primary Completion Date: Oct 1, 1994
• Actual Study Completion Date: Oct 1, 1994

Outcome Measures

Primary Outcome Measures

1. Effective Dose 50% (ED50) [15 minutes after each dose]

   ED50 is the cumulative dose of albuterol required to bring about 50% of maximum effect of albuterol

2. Effect Maximum (Emax) [15 minutes after each dose]

   Maximum percentage of predicted FEV1 effect

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nemours Children's Clinic	Jacksonville	Florida	United States	32207

Sponsors and Collaborators

• Nemours Children's Clinic

Investigators

• Principal Investigator: Kathryn V Blake, Pharm.D., Nemours Children's Clinic

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00940927
• Other Study ID Numbers: 93-41
• First Posted: Jul 17, 2009
• Last Update Posted: May 5, 2015
• Last Verified: Apr 1, 2015

• Keywords provided by , ,: Albuterol; Forced expiratory volume in one second; Dose at fifty percent of maximum effect; Maximum effective dose; Metered dose inhaler; Nebulizer
• Additional relevant MeSH terms: Asthma; Albuterol

Study Results

Participant Flow

Recruitment Details	Participants were recruited from our asthma research clinic database or newspaper advertisements. Participants were recruited from 07/1993 to 10/1994.
Pre-assignment Detail	Participants had to withhold inhaled short-acting beta2 agonist or inhaled anticholinergic drugs for 8 h, oral antihistamines for 5 days, theophylline for 24 h, and cromolyn, nedocromil, and inhaled corticosteroids for 2 h prior to the study.

Arm/Group Title	Albuterol
Arm/Group Description	Increasing doses of albuterol by MDI and nebulizer solution
Period Title: Overall Study
STARTED	81
COMPLETED	81
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Albuterol
Arm/Group Description	Increasing doses of albuterol by MDI and nebulizer solution
Overall Participants	81
Age (Count of Participants)
<=18 years	31 38.3%
Between 18 and 65 years	48 59.3%
>=65 years	2 2.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.2 (17.4)
Sex: Female, Male (Count of Participants)
Female	45 55.6%
Male	36 44.4%
Region of Enrollment (participants) [Number]
United States	81 100%

Outcome Measures

1. Primary Outcome

Title	Effective Dose 50% (ED50)
Description	ED50 is the cumulative dose of albuterol required to bring about 50% of maximum effect of albuterol
Time Frame	15 minutes after each dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Albuterol
Arm/Group Description	Increasing doses of albuterol by MDI and nebulizer solution
Measure Participants	81
Number [ug]	141

2. Primary Outcome

Title	Effect Maximum (Emax)
Description	Maximum percentage of predicted FEV1 effect
Time Frame	15 minutes after each dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Albuterol
Arm/Group Description	Increasing doses of albuterol by MDI and nebulizer solution
Measure Participants	81
Number [percentage of predicted]	24.0

Adverse Events

Arm/Group Title	Albuterol
Arm/Group Description	Increasing doses of albuterol by MDI and nebulizer solution
All Cause Mortality
	Albuterol
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Albuterol
	Affected / at Risk (%)	# Events
Total	0/81 (0%)
Other (Not Including Serious) Adverse Events
	Albuterol
	Affected / at Risk (%)	# Events
Total	0/81 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.