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

• ClinicalTrials.gov Identifier: NCT00448435
• Recruitment Status: Completed
• First Posted: March 16, 2007
• Results First Posted: August 11, 2009
• Last Update Posted: June 8, 2010
• Sponsor: GlaxoSmithKline
• Information provided by: GlaxoSmithKline

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Bronchial Asthma	Drug: GW815SF HFA MDI; Drug: salmeterol and fluticasone propionate	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 51 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: April 2007
• Actual Primary Completion Date: January 2008
• Actual Study Completion Date: January 2008

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: SLM+FP First; 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; salmeterol and fluticasone propionate combination; Other Name: salmeterol/fluticasone propionate combination; Drug: salmeterol and fluticasone propionate; salmeterol + fluticasone propionate
Active Comparator: SFC First; 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; salmeterol and fluticasone propionate combination; Other Name: salmeterol/fluticasone propionate combination; Drug: salmeterol and fluticasone propionate; salmeterol + fluticasone propionate
Experimental: SFC; SFC (salmeterol/fluticasone propionate combination) 25/50mcg twice daily in Extension period (after cross-over period).	Drug: GW815SF HFA MDI; salmeterol and fluticasone propionate combination; Other Name: salmeterol/fluticasone propionate combination

Outcome Measures

Primary Outcome Measures :

1. Adjusted Mean Change From Baseline in Morning PEF (Peak Expiratory Flow) During the 4-week Treatment Periods [ Time Frame: Crossover Period Weeks 1-4, and 7-10 ]
   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]).

Secondary Outcome Measures :

1. Adjusted Mean Change From Baseline in Percent Predicted Morning PEF(%) During the 4-week Treatment Periods [ Time Frame: Crossover Period Weeks 1-4, 7-10 ]
   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.
2. Adjusted Mean Change From Baseline in Percent Personal Best Morning PEF(%) During the 4-week Treatment Periods [ Time Frame: Crossover Period weeks 1-4, 7-10 ]
   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.
3. Adjusted Mean Change From Baseline in Evening PEF During the 4-week Treatment Periods [ Time Frame: Crossover Period weeks 1-4, 7-10 ]
   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.
4. Adjusted Mean Change From Baseline of Circadian Variation in Morning PEF(%) During the 4-week Treatment Periods [ Time Frame: Crossover Period Weeks 1-4, 7-10 ]
   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.
5. Percentage of Subjects With Symptom-Free Nights & Days [ Time Frame: Crossover Period Week 1-4, 7-10 ]
   Percentage of subjects with Symptom Free Nights & Days after 4 weeks of Treatment
6. Percentage of Subjects With Rescue Medication-Free Nights and Days [ Time Frame: Crossover Period Weeks 1-4, 7-10 ]
   Percentage of subjects with Rescue Medication Free Nights & Days after 4 weeks of Treatment
7. Adjusted Mean Change From Baseline in Morning PEF During the 20-week Extension Treatment Period [ Time Frame: Extension Period Weeks 11-30 ]
   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).
8. Adjusted Mean Change From Baseline in Percent Predicted Morning PEF(%) During the 20-Week Extension Treatment Period [ Time Frame: Extension Period weeks 11-30 ]
   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).
9. Adjusted Mean Change From Baseline in Percent Personal Best Morning PEF(%) During the 20-week Extension Treatment Period [ Time Frame: Extension Period weeks 11-30 ]
   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).
10. Adjusted Mean Change From Baseline in Evening PEF During the 20-week Extension Treatment Period [ Time Frame: Extension Period weeks 11-30 ]
    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).
11. Adjusted Mean Change From Baseline of Circadian Variation in PEF(%) During the 20-Week Extension Treatment Period [ Time Frame: Extension Period weeks 11-30 ]
    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).
12. Percentage of Subjects With Symptom-Free Nights & Days After 20 Weeks of Treatment [ Time Frame: Extension Period Weeks 11-30 ]
    Percentage of subjects with Symptom Free Nights & Days after 20 weeks of Treatment (at week 30).
13. Percentage of Subjects With Rescue Medication-Free Nights & Days After 20 Weeks of Treatment [ Time Frame: Extension Period Weeks 11-30 ]
    Percentage of subjects with Rescue Medication Free Nights & Days after 20 weeks of Treatment (at week 30).

Eligibility Criteria

• Ages Eligible for Study: 5 Years to 14 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

1. 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 .
2. Was able to perform entry in the asthma diary and PEF measurements in a correct manner in the investigator's/subinvestigator's judgment.
3. 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:

1. Admitted to the hospital due to asthma exacerbation during the run-in period.
2. Had upper or lower respiratory tract infection during the 2 weeks just before Visit 2.
3. Used prohibited drugs during the 2 weeks just before Visit 2.
4. 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:

1. Admitted to the hospital due to asthma exacerbation during the washout period.
2. Had upper or lower respiratory tract infection during the 2 weeks just before Visit 4.
3. Used prohibited drugs during the 2 weeks just before Visit 4.
4. Is not eligible for entry in Treatment Period 2 in the investigator's/subinvestigator's judgment.

Contacts and Locations

Locations

Japan

GSK Investigational Site

Chiba, Japan, 260-0001

GSK Investigational Site

Kanagawa, Japan, 245-0018

GSK Investigational Site

Saitama, Japan, 360-0018

GSK Investigational Site

Saitama, Japan, 360-0812

GSK Investigational Site

Tokyo, Japan, 154-0002

GSK Investigational Site

Tokyo, Japan, 154-0017

GSK Investigational Site

Tokyo, Japan, 158-0083

GSK Investigational Site

Tokyo, Japan, 158-0097

Sponsors and Collaborators

GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials; GlaxoSmithKline

More Information

• Responsible Party: Study Director, GSK
• ClinicalTrials.gov Identifier: NCT00448435
• Other Study ID Numbers: 110099
• First Posted: March 16, 2007
• Results First Posted: August 11, 2009
• Last Update Posted: June 8, 2010
• Last Verified: June 2010

Keywords provided by GlaxoSmithKline:

Salmeterol; Fluticasone propionate; Salmeterol/Fluticasone propionate combination; Pediatric bronchial asthma

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Fluticasone; Xhance; Salmeterol Xinafoate; Fluticasone-Salmeterol Drug Combination; Anti-Inflammatory Agents; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Dermatologic Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Glucocorticoids; Hormones