Dose-Response of Salmeterol in Children

Dose-response of Salmeterol Delivered by Advair Diskus in Children: Bioassay by Methacholine Challenge Using Oscillometry as the Endpoint

To examine whether a breathing test (methacholine challenge using impulse oscillometry) can be used to tell the difference between two different doses of an inhaled drug, salmeterol, delivered by Advair in children with asthma

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Advair Diskus100/50 µg; Drug: Methacholine Chloride; Drug: Albuterol; Drug: Flovent Diskus 100 µg

Detailed Description

During the study the subject will have to attend 4 study visits: 2 screening visits and 2 treatment visits.

Before each study visit, the subject has to stop using certain asthma medications.

At Screening Visit 1a, the parent/guardian will read and sign the informed consent form to allow the subject to take part in this study. The subject, if appropriate, will be asked to sign the last page to indicate his/her assent to be in the study.

The study coordinator will conduct an interview to find out about the subject's medical history, diseases other than asthma, previous medication and any medication that the subject will take during his/her participation in this study. Vital signs, i.e. blood pressure, heart rate, and respiration, and height and weight will be measured, and an electrocardiogram (ECG) which is a test to measure the electrical activity of the subject's heart, will be performed. The subject will be examined by a Pediatric Pulmonary physician and will be taught the proper way to use a Diskus® inhaler. The subject has to be able to show that he/she can do this correctly.

At Screening Visit 1b, if all of the tests are in the appropriate range the subject will take 2 puffs of Flovent from a Diskus®. One hour later, the subject will perform a breathing test called impulse oscillometry. Essentially, a sound is sent down into the lungs and a computer converts the return sound into a number. Then the subject will begin a breathing test with methacholine, a drug that makes the airways smaller. He/she will begin by inhaling a low dose in a nebulizer and then performing oscillometry. After a 5 minute interval he/she will breathe in increasing doses, up to 6 times or until his/her breathing test increases by 40%. Albuterol will be administered immediately after the end of the challenge and the subject will be monitored until his/her breathing returns to within 20% of where it was before the challenge.

If the methacholine test results are within the appropriate range the subject will be eligible for the treatment phase and will be scheduled for Visit No. 2.

At each treatment visit, the subject will take 2 puffs of study drug from two Diskus® inhalers, either 1 puff of Flovent and 1 puff of Advair, or 1 puff of Advair from two different inhalers. This is done in a blinded manner so the study coordinator does not know which treatment is used each time. There will be a 1 hour wait time after the medication is administered before the methacholine challenge is started. Albuterol will be administered immediately after the end of the challenge and the subject will be monitored until his/her breathing returns to within 20% of where it was before the challenge.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610-0486
      • University of Florida Asthma Research Lab

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 11 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• parent/legal guardian and subject must be able to speak and understand English and patient must be willing and able to give assent to take part in the study
• diagnosed with asthma for at least 6 months
• able to demonstrate inhalation technique with study device
• if taking inhaled corticosteroids, dose must be stable for 2 weeks
• no significant concomitant medical conditions or abnormal physical findings on screening except for those consistent with asthma and allergic rhinitis
• airway responsiveness to methacholine with a baseline provocational dose causing an increase of at least 40% in R5 (PC40R5) at no more than 8 mg/mL

Exclusion Criteria:

• female who has started menstruating
• past or present history of any allergic reaction to any of the medications or formulations administered in this study
• prior treatment with systemic corticosteroids in last 30 days or more than 4 courses in previous 12 months
• use of short-acting beta-agonist more than two times per week in the previous month
• use of long-acting beta-agonist in the 3 weeks before the first methacholine challenge or during the study
• change in dosage of inhaled corticosteroids in previous 30 days, nasal steroids in previous 15 days and montelukast in last 7 days
• history of life-threatening asthma, including loss of consciousness, intubation and/or admission to ICU
• hospitalization for acute asthma within past year
• inability to withhold the following medications before methacholine challenges:
• short-acting beta-agonists at least 6 hours
• regular long-acting beta-agonists at least 3 weeks
• inhaled corticosteroid at least 2 hours
• montelukast at least 24 hours
• aspirin and non-steroid anti-inflammatory drugs at least 48 hours
• caffeine at least 4 hours

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Advair Diskus100/50 µg and Advair Diskus 100/50 µg; The Advair Diskus 100/50 µg and Advair Diskus 100/50 µg will be administered in a blinded fashion. One hour after receiving the dose of Advair a methacholine challenge will be performed to determine the PC40R5. After the PC40R5 has been reached or a negative result after the highest methacholine concentration, 64 mg/mL, subjects will inhale albuterol through a valved holding chamber to reverse bronchoconstriction and their lung function will be monitored until it has returned to within 20% of that day's baseline R5.	Drug: Advair Diskus100/50 µg; Advair Diskus 100/50 µg; Other Names: fluticasone; salmeterol; Drug: Methacholine Chloride; Methacholine Chloride in quadrupling concentrations from 0.25 to 64 mg/mL will be given based upon subject's baseline response.; Drug: Albuterol; Albuterol will be administered at the end of each methacholine challenge.
ACTIVE_COMPARATOR: Advair Diskus 100/50 µg and Flovent Diskus 100 µg; The Advair Diskus 100/50 µg and Flovent Diskus 100 µg will be administered in a blinded fashion. One hour after receiving the dose of Advair and Flovent a methacholine challenge will be performed to determine the PC40R5. After the PC40R5 has been reached or a negative result after the highest methacholine concentration, 64 mg/mL, subjects will inhale albuterol through a valved holding chamber to reverse bronchoconstriction and their lung function will be monitored until it has returned to within 20% of that day's baseline R5.	Drug: Advair Diskus100/50 µg; Advair Diskus 100/50 µg; Other Names: fluticasone; salmeterol; Drug: Methacholine Chloride; Methacholine Chloride in quadrupling concentrations from 0.25 to 64 mg/mL will be given based upon subject's baseline response.; Drug: Albuterol; Albuterol will be administered at the end of each methacholine challenge.; Drug: Flovent Diskus 100 µg; Flovent Diskus 100 µg; Other Names: fluticasone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Airway Resistance Increase	concentration of methacholine required to increase total airway resistance by 40% (PC40R5)	1 to 7 days

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Teva Branded Pharmaceutical Products R&D, Inc.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (ACTUAL): May 1, 2014
• Study Completion (ACTUAL): July 1, 2014

Study Registration Dates

• First Submitted: June 28, 2013
• First Submitted That Met QC Criteria: July 18, 2013
• First Posted (ESTIMATE): July 24, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): October 7, 2014
• Last Update Submitted That Met QC Criteria: October 6, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: asthma; methacholine; oscillometry
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Dermatologic Agents; Cholinergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Sympathomimetics; Miotics; Parasympathomimetics; Bronchoconstrictor Agents; Muscarinic Agonists; Fluticasone; Xhance; Albuterol; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination; Methacholine Chloride
• Other Study ID Numbers: 38-2013