A Study of the Bronchodilator Effect of Formoterol Fumarate Used in Combination With Mometasone Furoate Metered Dose Inhaler in Children With Persistent Asthma (P06476 AM2)

Study Overview
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Brief Summary
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A study to compare the bronchodilatory effect of a single dose of Mometasone Furoate/Formoterol Fumarate (MF/F) pressurized metered dose inhaler (MDI) delivered with and without an AeroChamber Plus® with Flow-Vu® Anti-Static Valved Holding Chamber (spacer) versus Placebo MDI (combined with and without spacer) and formoterol fumarate (F) dry powder inhaler (DPI). Participants were randomly assigned to 1 of 6 treatment sequences and each participant was to receive a single dose of each of 4 treatments in each period. Each treatment period was separated by a 5 to 7 day washout period. It assumed that a single dose MF/F MDI 100/10 microgram (mcg) delivered with a spacer would produce bronchodilation, defined as a significant increase in forced expiratory volume in one second (FEV1) area under the curve from 0 to 12 hours (AUC[0-12 hr]) when compared to placebo.

Official Title
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A Randomized, Evaluator-Blind, Crossover, Single Dose Study of the Bronchodilator Effect of Formoterol Fumarate in Combination With Mometasone Furoate Metered Dose Inhaler Delivered With and Without a Spacer Versus Placebo and Foradil® Aerolizer® in Children With Persistent Asthma (Protocol No. P06476)

Conditions
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Asthma

Intervention / Treatment
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* Drug: Formoterol Fumarate DPI
* Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer
* Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer
* Drug: Placebo MDI with spacer
* Drug: Placebo MDI without spacer
* Drug: Mometasone Furoate DPI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have a diagnosis of asthma of at least 6 months duration Must have taken an Inhaled Corticosteroid ([ICS]; alone or in combination with a long-acting beta-2 Agonist [LABA]) for at least 3 months prior to the Screening Visit and must have been on a stable daily dose for at least 2 weeks prior to the Screening Visit FEV1 must be at least 70% predicted after all restricted medications have been withheld for the appropriate intervals Must demonstrate an increase in absolute FEV1 of at least 12% within 30 minutes after administration of 360 mcg albuterol (4 inhalations x 90 mcg, ex-actuator) or of nebulized albuterol (2.5 mg), if confirmed as standard office practice Exclusion Criteria: Has been treated in the emergency room for a severe asthma exacerbation requiring systemic glucocorticosteroid treatment, or hospitalized for management of airway obstruction within 3 months prior to the Screening Visit Has required ventilator support for respiratory failure secondary to asthma Demonstrates a decrease in absolute FEV1 of >20% at any time from the Screening Visit up to and including the Baseline Visit Requires the use of greater than 8 inhalations per day of short-acting beta-2 agonists (SABA) MDI, or 2 or more nebulized treatments per day of 2.5 mg SABA on any 2 consecutive days from the Screening Visit up to and including the Baseline Visit Experiences a clinical deterioration in asthma that results in emergency treatment, hospitalization due to asthma, or treatment with additional, excluded asthma medication (including oral or other systemic corticosteroids, but allowing SABA) as judged by the investigator, at any time from the Screening Visit up to and including the Baseline Visit

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequence 1<br>Treatment Period 1: Placebo MDI with spacer; Treatment Period 2: MF/F MDI without spacer; Treatment Period 3: MF/F MDI with spacer; Treatment Period 4: F DPI | Drug: Formoterol Fumarate DPI<br>* Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose<br>* Other names: Foradil® Aerolizer®;Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer<br>* Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>* Other names: MK-0877A;Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer<br>* Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>* Other names: MK-0877A;Drug: Placebo MDI with spacer<br>* Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>Drug: Mometasone Furoate DPI<br>* Two inhalations of MF DPI 100 mcg administered as a single dose once daily at night. Used as maintenance therapy during screening and in between single doses of study drug.<br>* Other names: Asmanex® Twisthaler®;|
| Experimental: Sequence 2<br>Treatment Period 1: F DPI; Treatment Period 2: MF/F MDI without spacer; Treatment Period 3: MF/F MDI with spacer; Treatment Period 4: Placebo MDI with spacer | Drug: Formoterol Fumarate DPI<br>* Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose<br>* Other names: Foradil® Aerolizer®;Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer<br>* Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>* Other names: MK-0877A;Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer<br>* Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>* Other names: MK-0877A;Drug: Placebo MDI with spacer<br>* Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>Drug: Mometasone Furoate DPI<br>* Two inhalations of MF DPI 100 mcg administered as a single dose once daily at night. Used as maintenance therapy during screening and in between single doses of study drug.<br>* Other names: Asmanex® Twisthaler®;|
| Experimental: Sequence 3<br>Treatment Period 1: MF/F MDI without spacer; Treatment Period 2: F DPI; Treatment Period 3: Placebo MDI with spacer; Treatment Period 4: MF/F MDI with spacer | Drug: Formoterol Fumarate DPI<br>* Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose<br>* Other names: Foradil® Aerolizer®;Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer<br>* Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>* Other names: MK-0877A;Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer<br>* Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>* Other names: MK-0877A;Drug: Placebo MDI with spacer<br>* Two inhalations of placebo MDI administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>Drug: Mometasone Furoate DPI<br>* Two inhalations of MF DPI 100 mcg administered as a single dose once daily at night. Used as maintenance therapy during screening and in between single doses of study drug.<br>* Other names: Asmanex® Twisthaler®;|
| Experimental: Sequence 4<br>Treatment Period 1: Placebo MDI without spacer; Treatment Period 2: MF/F MDI with spacer; Treatment Period 3: F DPI; Treatment Period 4: MF/F MDI without spacer | Drug: Formoterol Fumarate DPI<br>* Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose<br>* Other names: Foradil® Aerolizer®;Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer<br>* Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>* Other names: MK-0877A;Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer<br>* Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>* Other names: MK-0877A;Drug: Placebo MDI without spacer<br>* Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>Drug: Mometasone Furoate DPI<br>* Two inhalations of MF DPI 100 mcg administered as a single dose once daily at night. Used as maintenance therapy during screening and in between single doses of study drug.<br>* Other names: Asmanex® Twisthaler®;|
| Experimental: Sequence 5<br>Treatment Period 1: MF/F MDI without spacer; Treatment Period 2: F DPI; Treatment Period 3: MF/F MDI with spacer; Treatment Period 4: Placebo MDI without spacer | Drug: Formoterol Fumarate DPI<br>* Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose<br>* Other names: Foradil® Aerolizer®;Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer<br>* Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>* Other names: MK-0877A;Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer<br>* Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>* Other names: MK-0877A;Drug: Placebo MDI without spacer<br>* Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>Drug: Mometasone Furoate DPI<br>* Two inhalations of MF DPI 100 mcg administered as a single dose once daily at night. Used as maintenance therapy during screening and in between single doses of study drug.<br>* Other names: Asmanex® Twisthaler®;|
| Experimental: Sequence 6<br>Treatment Period 1: MF/F MDI with spacer; Treatment Period 2: Placebo MDI without spacer; Treatment Period 3: MF/F MDI without spacer; Treatment Period 4: F DPI | Drug: Formoterol Fumarate DPI<br>* Two inhalations of Formoterol Fumarate DPI 10 mcg administered as a single dose<br>* Other names: Foradil® Aerolizer®;Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) without spacer<br>* Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>* Other names: MK-0877A;Drug: Mometasone Furoate/Formoterol Fumarate MDI (ex-actuator) with spacer<br>* Two inhalations of Mometasone Furoate/Formoterol Fumarate MDI 50/5 mcg administered as a single dose with an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>* Other names: MK-0877A;Drug: Placebo MDI without spacer<br>* Two inhalations of placebo MDI administered as a single dose without an AeroChamber Plus® Flow-Vu® Anti-Static Valved Holding Chamber (spacer)<br>Drug: Mometasone Furoate DPI<br>* Two inhalations of MF DPI 100 mcg administered as a single dose once daily at night. Used as maintenance therapy during screening and in between single doses of study drug.<br>* Other names: Asmanex® Twisthaler®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve From 0-12 Hours (AUC[0-12h]) of the Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) After a Single Dose of MF/F MDI With Spacer Compared to Placebo MDI Combined With or Without Spacer | The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. | Up to 12 hours postdose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC(0-12h) of the Change From Baseline in FEV1 After a Single Dose MF/F MDI Without Spacer Compared to Placebo MDI Combined With or Without Spacer | The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. | Up to 12 hours postdose | 
| AUC(0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer Compared to MF/F MDI Without Spacer | The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. | Up to 12 hours postdose | 
| Change From Baseline in FEV1 After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | Baseline was defined as the average of 2 predose measurements (taken 30 minutes and immediately before dosing). | Baseline and 5 and 30 minutes, 1, 2, 4, 8 and 12 hours postdose | 
| AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F With Spacer Compared to F DPI | The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. | Up to 12 hours postdose | 
| AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of MF/F Without Spacer Compared to F DPI | The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. | Up to 12 hours postdose | 
| AUC (0-12h) of the Change From Baseline in FEV1 After a Single Dose of F DPI Compared to Placebo MDI Combined With or Without Spacer | The AUC was standardized to liters by dividing the length of time for which measurements of FEV1 were included in the calculation of the AUC. Baseline was defined as the average of 2 pre-dose FEV1 measurements (taken 30 minutes before and immediately before dosing), which was subtracted from each of the serial FEV1 measurements over the 12-hour period. The AUC was calculated based on these changes from the baseline evaluations using the trapezoidal rule. | Up to 12 hours postdose | 
| Change From Baseline in Forced Vital Capacity (FVC) After a Single Dose of MF/F MDI With Spacer, MF/F MDI Without Spacer, F DPI or Placebo MDI Combined With or Without Spacer at 5 and 30 Minutes, 1, 2, 4, 8 and 12 Hours Postdose | Baseline was defined as the average of 2 predose FVC measurements (taken 30 minutes and immediately before dosing). | Baseline and 5 and 30 minutes, 1, 2, 4, 8 and 12 hours postdose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, children, persistent