Clinical Assessment Of GW815SF HFA MDI In Pediatric Patients With Bronchial Asthma

Study Overview
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Brief Summary
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To evaluate the efficacy and safety of GW815SF HFA MDI 25/50µg 1 inhalation bid in comparison with concomitant treatment with salmeterol xinafoate DPI 25µg 1 inhalation bid plus fluticasone propionate DPI 50µg 1 inhalation bid in paediatric patients with asthma. To evaluate the safety of long-term treatment of GW815SF HFA MDI 25/50µg 1 inhalation bid in paediatric patients with asthma.

Official Title
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A Study to Compare GW815SF HFA MDI With Concomitant Treatment With Salmeterol Xinafoate DPI Plus Fluticasone Propionate DPI and to Assess Long-term Safety of GW815SF HFA MDI

Conditions
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Bronchial Asthma

Intervention / Treatment
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* Drug: GW815SF HFA MDI
* Drug: salmeterol and fluticasone propionate


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Inclusion Criteria for Entry in Run-in Period A pediatric patient already diagnosed as having bronchial asthma who meets all of the following criteria is eligible for the study: Male or female patients aged ≥5 and ≤14 years. Enrolment of a female patient of childbearing potential is allowed only if she is tested negative in the pregnancy testing at the start of Treatment Period 1 and if she agrees to undergo pregnancy testing at the protocol-specified timings and to take contraceptive measures without fail. Written informed consent must be obtained from a legally acceptable representative of the subject. Consent of the subject him/herself should also be obtained, wherever possible, after giving an explanation in an as easy to understand as possible manner. An outpatient who has been treated with ICS (FP 100μg/day or equivalent) for at least 4 weeks prior to Visit 1. Able to use a peak flow meter in a correct manner in the investigator's/subinvestigator's judgment. Able to use MDI and DPI in a correct manner (with the assistance of his/her caregiver as necessary) in the investigator's/subinvestigator's judgment. Inclusion Criteria for Entry in Treatment Period 1 A subject will be randomized to one of the two treatment groups only if he/she has completed the run-in period and meets all the following criteria. Has a mean of morning PEF measurements in the last 7 days of the run-in period (excluding the first day of Treatment Period 1) ≤90% of his/her best PEF measurement . Was able to perform entry in the asthma diary and PEF measurements in a correct manner in the investigator's/subinvestigator's judgment. Able to use MDI and DPI in a correct manner (with the assistance of his/her caregiver as necessary) in the investigator's/subinvestigator's judgment. Exclusion criteria: Exclusion Criteria for Entry in Run-in Period A patient who applies any of the following criteria is not eligible for the study: Admitted to the hospital due to asthma exacerbation within 8 weeks prior to Visit 1. Used systemic steroid within 4 weeks prior to Visit 1. Received antibacterials or antivirals for treatment of upper or lower respiratory tract infection within 2 weeks prior to Visit 1. Has a safety problem in participation in the study because of a serious, uncontrolled systemic disease including nervous system disorder. Has or is suspected to have deep-seated mycosis or infection to which no effective antibacterial agent is available. Has or is suspected to have hypersensitivity to the investigational product, rescue medication or any ingredients of them. Is pregnant or lactating, may be pregnant, or plans for pregnancy during the study period. Has received the last dose in another clinical study within 2 months prior to this study. Is not eligible for the study in the investigator's/subinvestigator's judgment. Exclusion Criteria for Entry in Treatment Period 1 Enrolment of a subject completing the run-in period into Treatment Period 1 will not be allowed if any of the following applies: Admitted to the hospital due to asthma exacerbation during the run-in period. Had upper or lower respiratory tract infection during the 2 weeks just before Visit 2. Used prohibited drugs during the 2 weeks just before Visit 2. Is not eligible for the study in the investigator's/subinvestigator's judgment. Exclusion Criteria for Entry in Treatment Period 2 Enrolment of a subject completing the washout period into Treatment Period 2 will not be allowed if any of the following applies: Admitted to the hospital due to asthma exacerbation during the washout period. Had upper or lower respiratory tract infection during the 2 weeks just before Visit 4. Used prohibited drugs during the 2 weeks just before Visit 4. Is not eligible for entry in Treatment Period 2 in the investigator's/subinvestigator's judgment.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 14 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: SLM+FP First<br>SLM(salmeterol) 25mcg + FP(fluticasone propionate) 50mcg twice daily in first intervention period and SFC(salmeterol/fluticasone propionate) 25/50mcg twice daily in second intervention period and (after washout period). | Drug: GW815SF HFA MDI<br>* salmeterol and fluticasone propionate combination<br>* Other names: salmeterol/fluticasone propionate combination;Drug: salmeterol and fluticasone propionate<br>* salmeterol + fluticasone propionate<br>|
| Active Comparator: SFC First<br>SFC (Salmeterol/Fluticasone propionate combination) 25/50mcg twice daily in first intervention period and SLM (Salmeterol) 25mcg + FP (Fluticasone Propionate) 50mcg twice daily in second intervention period (after washout period). | Drug: GW815SF HFA MDI<br>* salmeterol and fluticasone propionate combination<br>* Other names: salmeterol/fluticasone propionate combination;Drug: salmeterol and fluticasone propionate<br>* salmeterol + fluticasone propionate<br>|
| Experimental: SFC<br>SFC (salmeterol/fluticasone propionate combination) 25/50mcg twice daily in Extension period (after cross-over period). | Drug: GW815SF HFA MDI<br>* salmeterol and fluticasone propionate combination<br>* Other names: salmeterol/fluticasone propionate combination;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change From Baseline in Morning PEF (Peak Expiratory Flow) During the 4-week Treatment Periods | Mean change from baseline = value at each assessment period (mean of the values obtained at each assessment period [Weeks 1-4/Weeks 7-10]) minus baseline value. Baseline: Mean of the daily values over the last 7 days of the 2-week run-in/wash-out (i.e., the last 7 days prior to the day of starting treatment period [Weeks 1-4/Weeks 7-10]). | Crossover Period Weeks 1-4, and 7-10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjusted Mean Change From Baseline in Percent Predicted Morning PEF(%) During the 4-week Treatment Periods | Mean change from baseline = value at each assessment period (mean of the values obtained at each assessment period [Weeks 1-4/Weeks 7-10]) minus baseline value. Baseline: Mean of the daily values over the last 7 days of the 2-week run-in/wash-out. | Crossover Period Weeks 1-4, 7-10 | 
| Adjusted Mean Change From Baseline in Percent Personal Best Morning PEF(%) During the 4-week Treatment Periods | Mean change from baseline = value at each assessment period (mean of the values obtained at each assessment period [Weeks 1-4/Weeks 7-10]) minus baseline value. Baseline: Mean of the daily values over the last 7 days of the 2-week run-in/wash-out. | Crossover Period weeks 1-4, 7-10 | 
| Adjusted Mean Change From Baseline in Evening PEF During the 4-week Treatment Periods | Mean change from baseline = value at each assessment period (mean of the values obtained at each assessment period [Weeks 1-4/Weeks 7-10]) minus baseline value. Baseline: Mean of the daily values over the last 7 days of the 2-week run-in/wash-out. | Crossover Period weeks 1-4, 7-10 | 
| Adjusted Mean Change From Baseline of Circadian Variation in Morning PEF(%) During the 4-week Treatment Periods | Mean change from baseline = value at each assessment period (mean of the values obtained at each assessment period [Weeks 1-4/Weeks 7-10]) minus baseline value. Baseline: Mean of the daily values over the last 7 days of the 2-week run-in/wash-out. | Crossover Period Weeks 1-4, 7-10 | 
| Percentage of Subjects With Symptom-Free Nights & Days | Percentage of subjects with Symptom Free Nights & Days after 4 weeks of Treatment | Crossover Period Week 1-4, 7-10 | 
| Percentage of Subjects With Rescue Medication-Free Nights and Days | Percentage of subjects with Rescue Medication Free Nights & Days after 4 weeks of Treatment | Crossover Period Weeks 1-4, 7-10 | 
| Adjusted Mean Change From Baseline in Morning PEF During the 20-week Extension Treatment Period | Mean change from baseline = value at assessment period (mean of the values obtained at assessment period (Weeks 11-30).) minus baseline value. Baseline: Mean of the daily values over the last 7 days prior to the day of starting of the Extension period (Weeks 11-30). | Extension Period Weeks 11-30 | 
| Adjusted Mean Change From Baseline in Percent Predicted Morning PEF(%) During the 20-Week Extension Treatment Period | Mean change from baseline = value at assessment period (mean of the values obtained at assessment period [Weeks 11-30]) minus baseline value. Baseline: Mean of the daily values over the last 7 days prior to the day of starting the Extension period (Weeks 11-30). | Extension Period weeks 11-30 | 
| Adjusted Mean Change From Baseline in Percent Personal Best Morning PEF(%) During the 20-week Extension Treatment Period | Mean change from baseline = value at assessment period (mean of the values obtained at assessment period [Weeks 11-30]) minus baseline value. Baseline: Mean of the daily values over the last 7 days prior to the day of starting the Extension period (Weeks 11-30). | Extension Period weeks 11-30 | 
| Adjusted Mean Change From Baseline in Evening PEF During the 20-week Extension Treatment Period | Mean change from baseline = value at assessment period (mean of the values obtained at assessment period [Weeks 11-30]) minus baseline value. Baseline: Mean of the daily values over the last 7 days prior to the day of starting the Extension period (Weeks 11-30). | Extension Period weeks 11-30 | 
| Adjusted Mean Change From Baseline of Circadian Variation in PEF(%) During the 20-Week Extension Treatment Period | Mean change from baseline = value at assessment period (mean of the values obtained at assessment period [Weeks 11-30]) minus baseline value. Baseline: Mean of the daily values over the last 7 days prior to the day of starting the Extension period (Weeks 11-30). | Extension Period weeks 11-30 | 
| Percentage of Subjects With Symptom-Free Nights & Days After 20 Weeks of Treatment | Percentage of subjects with Symptom Free Nights & Days after 20 weeks of Treatment (at week 30). | Extension Period Weeks 11-30 | 
| Percentage of Subjects With Rescue Medication-Free Nights & Days After 20 Weeks of Treatment | Percentage of subjects with Rescue Medication Free Nights & Days after 20 weeks of Treatment (at week 30). | Extension Period Weeks 11-30 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Salmeterol, Fluticasone propionate, Salmeterol/Fluticasone propionate combination, Pediatric bronchial asthma