A Study of Mometasone Furoate Metered Dose Inhaler in Children With Persistent Asthma (P04223)

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to demonstrate the dose-related efficacy, by evaluating morning (AM) lung function at the end of the dosing interval (AM pre-dose percent predicted forced expiratory volume in one second [FEV1]) across 12 weeks of treatment, of three doses (50 mcg, 100 mcg, and 200 mcg) of Mometasone Furoate (MF) Metered Dose Inhaler (MDI) twice a day (BID) compared with Placebo in children 5 to 11 years of age, inclusive, with persistent asthma. The primary hypothesis of this study is that at least one dose of MF MDI BID increases lung function, defined as a significant increase in percent predicted FEV1, when compared to Placebo.

Official Title
-----------------
A 12-Week, Randomized, Placebo-Controlled, Dose-Ranging, Efficacy and Safety Study of Mometasone Furoate Metered Dose Inhaler in the Treatment of Children Ages 5 to 11 Years With Persistent Asthma (Phase 2; Protocol No. P04223AM3)

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Drug: Mometasone Furoate (MF) Metered Dose Inhaler (MDI), 25 mcg
* Drug: Mometasone Furoate (MF) Metered Dose Inhaler (MDI), 50 mcg
* Drug: Mometasone Furoate (MF) Metered Dose Inhaler (MDI), 100 mcg
* Drug: Mometasone Furoate (MF) Dry Powder Inhaler (DPI), 100 mcg
* Drug: Placebo Metered Dose Inhaler (MDI)
* Drug: Placebo Dry Powder Inhaler (DPI)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of asthma of at least 6 months duration. Using an Inhaled corticosteroid (ICS), either alone or in combination with a long-acting beta-2 agonist (LABA), for at least 12 weeks prior to the Screening Visit and must have been on a stable asthma regimen for at least 2 weeks prior to the Screening Visit, must not have used oral glucocorticosteroids within 30 days of the Screening Visit. Exclusion Criteria: Treated in the emergency room for a severe asthma exacerbation requiring systemic glucocorticosteroid treatment, or hospitalization for management of airway obstruction within 3 months prior to the Screening Visit. History of ventilator support for respiratory failure secondary to asthma. Upper or lower respiratory tract infection (viral or bacterial) within the 2 weeks prior to Screening and Baseline Visits. History of clinically significant renal, hepatic, cardiovascular, metabolic, neurologic, hematologic, ophthalmologic, respiratory, gastrointestinal, cerebrovascular, or other significant medical illness or disorder which, in the judgment of the investigator, could interfere with the study or require treatment that might interfere with the study. Specific examples include but are not limited to insulin-dependent diabetes, hypertension, active hepatitis, cardiovascular disease including hypertension, or conditions that may interfere with respiratory function such as, bronchiectasis, and cystic fibrosis. Other conditions that are well controlled and stable will not prohibit participation if deemed appropriate per the investigator's judgment. Inability to correctly use an oral MDI or a DPI. Participation in this study at another investigational site. Participation in a different investigational study at any site during the same time frame of this study. Randomization into this study more than once. Direct association with either the administration of the this study or the study staff.

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

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MF MDI 50 mcg BID<br>Participants receive MF MDI 25 mcg x 2 inhalations (50 mcg total dose) BID PLUS Placebo dry powder inhaler (DPI) x 1 inhalation once daily (QD) in the evening for 12 weeks. | Drug: Mometasone Furoate (MF) Metered Dose Inhaler (MDI), 25 mcg<br>* MF MDI 25 mcg (per inhalation), 2 puffs BID for 12 weeks<br>Drug: Placebo Dry Powder Inhaler (DPI)<br>* Placebo DPI, 1 puff QD for 12 weeks<br>|
| Experimental: MF MDI 100 mcg BID<br>Participants receive MF MDI 50 mcg x 2 inhalations (100 mcg total dose) BID PLUS Placebo DPI x 1 inhalation QD in the evening for 12 weeks. | Drug: Mometasone Furoate (MF) Metered Dose Inhaler (MDI), 50 mcg<br>* MF MDI 50 mcg (per inhalation), 2 puffs BID for 12 weeks<br>Drug: Placebo Dry Powder Inhaler (DPI)<br>* Placebo DPI, 1 puff QD for 12 weeks<br>|
| Experimental: MF MDI 200 mcg BID<br>Participants receive MF MDI 100 mcg x 2 inhalations (200 mcg total dose) BID PLUS Placebo DPI x 1 inhalation QD in the evening for 12 weeks. | Drug: Mometasone Furoate (MF) Metered Dose Inhaler (MDI), 100 mcg<br>* MF MDI 100 mcg (per inhalation), 2 puffs BID for 12 weeks<br>Drug: Placebo Dry Powder Inhaler (DPI)<br>* Placebo DPI, 1 puff QD for 12 weeks<br>|
| Active Comparator: MF DPI 100 mcg QD<br>Participants receive Placebo MDI x 2 inhalations BID PLUS MF DPI x 1 inhalation QD in the evening for 12 weeks. | Drug: Mometasone Furoate (MF) Dry Powder Inhaler (DPI), 100 mcg<br>* MF DPI 100 mcg (per inhalation), 1 puff QD for 12 weeks<br>* Other names: Asmanex® Twisthaler®;Drug: Placebo Metered Dose Inhaler (MDI)<br>* Placebo MDI, 2 puffs BID for 12 weeks<br>|
| Placebo Comparator: Placebo<br>Participants receive Placebo MDI x 2 inhalations BID PLUS Placebo DPI x 1 inhalation QD in the evening for 12 weeks. | Drug: Placebo Metered Dose Inhaler (MDI)<br>* Placebo MDI, 2 puffs BID for 12 weeks<br>Drug: Placebo Dry Powder Inhaler (DPI)<br>* Placebo DPI, 1 puff QD for 12 weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Percent Predicted Morning (AM) Forced Expiratory Volume in 1 Second (FEV1) - MF MDI vs. Placebo | FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second. Pulmonary function tests were to be performed by participants in the morning before dosing. The percent predicted FEV1 equals the participant's observed FEV1 divided by the participant's predicted FEV1 (determined by height and race) and converted to a percentage by multiplying by 100%. The goal of the primary outcome measure was to compare the change from Baseline in AM FEV1 between the MF MDI and Placebo treatment groups. The comparison between the MF MDI 50 mcg BID vs. MF DPI 100 mcg QD treatment groups is presented in a subsequent outcome measure. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in AM Peak Expiratory Flow (PEF) - MF MDI vs. Placebo | PEF, measured in liters per minute, is the highest flow during exhalation. Participants recorded diary entries for PEF twice daily (in the morning upon rising and in the evening at bedtime). The goal of the secondary outcome measure was to compare the change from Baseline in AM PEF between the MF MDI and Placebo treatment groups. | Baseline and Week 12 | 
| Change From Baseline in Paediatric Asthma Quality of Life Questionnaire With Standardised Activities (PAQLQ(S)) Total Score - MF MDI vs. Placebo | The PAQLQ(S) consists of 23 questions in 3 categories: Symptoms (10 items), Activity Limitations (5 items), and Emotional Function (8 items). Responses are based on a 7-point scale (7=not bothered at all to 1=extremely bothered). PAQLQ(S) Total Scores could range from 23 to 161, with a lower score indicating a lower quality of life. The PAQLQ(S) included only participants in participating countries in which a validated translated questionnaire was available. The goal of the secondary outcome measure was to compare the change from Baseline in PAQLQ(S) between the MF MDI and Placebo treatment groups. | Baseline and Week 12 | 
| Change From Baseline in Percent Predicted AM FEV1 - MF MDI 50 mcg BID vs. MF DPI 100 mcg QD | FEV1 is the amount of air, measured in liters, forcibly exhaled in 1 second. Pulmonary function tests were to be performed by participants in the morning before dosing. The percent predicted FEV1 equals the participant's observed FEV1 divided by the participant's predicted FEV1 (determined by height and race) and converted to a percentage by multiplying by 100%. The goal of the secondary outcome measure was to compare the change from Baseline in AM FEV1 between the MF MDI 50 mcg BID and MF DPI 100 mcg QD treatment groups. The comparisons between the other MF MDI BID and Placebo treatment groups are presented in a previous outcome measure. | Baseline and Week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Asthma, Children, Persistent