Bronchial Asthma
Conditions
Keywords
Salmeterol, Fluticasone propionate, Salmeterol/Fluticasone propionate combination, Pediatric bronchial asthma
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.
Interventions
DRUGGW815SF HFA MDI
salmeterol and fluticasone propionate combination
salmeterol + fluticasone propionate
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 14 Years
Healthy volunteers
No
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
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change From Baseline in Morning PEF (Peak Expiratory Flow) During the 4-week Treatment Periods | 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
| Measure | Time frame | Description |
|---|---|---|
| Adjusted Mean Change From Baseline in Percent Personal Best Morning PEF(%) During the 4-week Treatment Periods | 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. |
| Adjusted Mean Change From Baseline in Evening PEF During the 4-week Treatment Periods | 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. |
| Adjusted Mean Change From Baseline of Circadian Variation in Morning PEF(%) During the 4-week Treatment Periods | 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. |
| Percentage of Subjects With Symptom-Free Nights & Days | Crossover Period Week 1-4, 7-10 | Percentage of subjects with Symptom Free Nights & Days after 4 weeks of Treatment |
| Percentage of Subjects With Rescue Medication-Free Nights and Days | Crossover Period Weeks 1-4, 7-10 | Percentage of subjects with Rescue Medication Free Nights & Days after 4 weeks of Treatment |
| Adjusted Mean Change From Baseline in Morning PEF During the 20-week Extension Treatment Period | 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). |
| Adjusted Mean Change From Baseline in Percent Predicted Morning PEF(%) During the 4-week Treatment Periods | 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. |
| Adjusted Mean Change From Baseline in Percent Personal Best Morning PEF(%) During the 20-week Extension Treatment Period | 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). |
| Adjusted Mean Change From Baseline in Evening PEF During the 20-week Extension Treatment Period | 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). |
| Adjusted Mean Change From Baseline of Circadian Variation in PEF(%) During the 20-Week Extension Treatment Period | 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). |
| Percentage of Subjects With Symptom-Free Nights & Days After 20 Weeks of Treatment | Extension Period Weeks 11-30 | Percentage of subjects with Symptom Free Nights & Days after 20 weeks of Treatment (at week 30). |
| Percentage of Subjects With Rescue Medication-Free Nights & Days After 20 Weeks of Treatment | Extension Period Weeks 11-30 | Percentage of subjects with Rescue Medication Free Nights & Days after 20 weeks of Treatment (at week 30). |
| Adjusted Mean Change From Baseline in Percent Predicted Morning PEF(%) During the 20-Week Extension Treatment Period | 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). |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Overall Study Population Randomized Population | 51 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Washout Period - 2 Weeks | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Overall Study Population |
|---|---|
| Age Continuous | 8.3 Years STANDARD_DEVIATION 2.41 |
| Race/Ethnicity, Customized Asian-Japanese Heritage | 51 Participants |
| Region of Enrollment Japan | 51 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 12 / 51 | 10 / 50 | 35 / 51 |
| serious Total, serious adverse events | 0 / 51 | 0 / 50 | 0 / 51 |
Outcome results
Primary
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 \[Weeks 1-4/Weeks 7-10\]).
Time frame: Crossover Period Weeks 1-4, and 7-10
Population: PPS (Per Protocol Set): randomized subjects less those who did not complete treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SFC 50/100 Mcg/Day | Adjusted Mean Change From Baseline in Morning PEF (Peak Expiratory Flow) During the 4-week Treatment Periods | 14.3 Liters/minute | Standard Error 4.53 |
| SLM 50 Mcg + FP 100 Mcg/Day | Adjusted Mean Change From Baseline in Morning PEF (Peak Expiratory Flow) During the 4-week Treatment Periods | 17.1 Liters/minute | Standard Error 4.53 |
Comparison: Difference between treatments \[(SLM + FP)- SFC\](SE) 2.8 (5.91)p-value: 0.638395% CI: [-9.1, 14.69]Mixed Models Analysis
Secondary
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).
Time frame: Extension Period weeks 11-30
Population: FAS (Full Analysis Set) during the Exension period: all subjects switched to Extension period and received GW815SF HFA MDI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SFC 50/100 Mcg/Day | Adjusted Mean Change From Baseline in Evening PEF During the 20-week Extension Treatment Period | 2.7 L/Min | Standard Deviation 23.43 |
Secondary
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.
Time frame: Crossover Period weeks 1-4, 7-10
Population: PPS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SFC 50/100 Mcg/Day | Adjusted Mean Change From Baseline in Evening PEF During the 4-week Treatment Periods | 16.3 L/min | Standard Error 3.74 |
| SLM 50 Mcg + FP 100 Mcg/Day | Adjusted Mean Change From Baseline in Evening PEF During the 4-week Treatment Periods | 15.8 L/min | Standard Error 3.74 |
Secondary
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).
Time frame: Extension Period Weeks 11-30
Population: FAS (Full Analysis Set) during the Extension period: all subjects switched to Extension period and received GW815SF HFA MDI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SFC 50/100 Mcg/Day | Adjusted Mean Change From Baseline in Morning PEF During the 20-week Extension Treatment Period | 3.0 L/min | Standard Deviation 24.56 |
Secondary
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).
Time frame: Extension Period weeks 11-30
Population: FAS (Full Analysis Set) during the Extension period: all subjects switched to Extension period and received GW815SF HFA MDI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SFC 50/100 Mcg/Day | Adjusted Mean Change From Baseline in Percent Personal Best Morning PEF(%) During the 20-week Extension Treatment Period | 1.29 Percentage of personal best value | Standard Deviation 8.541 |
Secondary
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.
Time frame: Crossover Period weeks 1-4, 7-10
Population: PPS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SFC 50/100 Mcg/Day | Adjusted Mean Change From Baseline in Percent Personal Best Morning PEF(%) During the 4-week Treatment Periods | 5.01 Percentage of personal best value | Standard Error 1.48 |
| SLM 50 Mcg + FP 100 Mcg/Day | Adjusted Mean Change From Baseline in Percent Personal Best Morning PEF(%) During the 4-week Treatment Periods | 6.46 Percentage of personal best value | Standard Error 1.48 |
Secondary
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).
Time frame: Extension Period weeks 11-30
Population: FAS (Full Analysis Set) during the Extension period: all subjects switched to Extension period and received GW815SF HFA MDI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SFC 50/100 Mcg/Day | Adjusted Mean Change From Baseline in Percent Predicted Morning PEF(%) During the 20-Week Extension Treatment Period | 1.46 Percentage of predicted value | Standard Deviation 9.568 |
Secondary
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.
Time frame: Crossover Period Weeks 1-4, 7-10
Population: PPS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SFC 50/100 Mcg/Day | Adjusted Mean Change From Baseline in Percent Predicted Morning PEF(%) During the 4-week Treatment Periods | 5.38 Percentage of predicted value | Standard Error 1.543 |
| SLM 50 Mcg + FP 100 Mcg/Day | Adjusted Mean Change From Baseline in Percent Predicted Morning PEF(%) During the 4-week Treatment Periods | 6.73 Percentage of predicted value | Standard Error 1.543 |
Secondary
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.
Time frame: Crossover Period Weeks 1-4, 7-10
Population: PPS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SFC 50/100 Mcg/Day | Adjusted Mean Change From Baseline of Circadian Variation in Morning PEF(%) During the 4-week Treatment Periods | 0.06 Percentage of circadian variation | Standard Error 0.638 |
| SLM 50 Mcg + FP 100 Mcg/Day | Adjusted Mean Change From Baseline of Circadian Variation in Morning PEF(%) During the 4-week Treatment Periods | -0.08 Percentage of circadian variation | Standard Error 0.638 |
Secondary
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).
Time frame: Extension Period weeks 11-30
Population: FAS (Full Analysis Set) during the Extension period: all subjects switched to Extension period and received GW815SF HFA MDI.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| SFC 50/100 Mcg/Day | Adjusted Mean Change From Baseline of Circadian Variation in PEF(%) During the 20-Week Extension Treatment Period | -0.37 Percentage of circadian variation | Standard Deviation 3.568 |
Secondary
Percentage of Subjects With Rescue Medication-Free Nights and Days
Percentage of subjects with Rescue Medication Free Nights & Days after 4 weeks of Treatment
Time frame: Crossover Period Weeks 1-4, 7-10
Population: PPS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SFC 50/100 Mcg/Day | Percentage of Subjects With Rescue Medication-Free Nights and Days | Baseline | 87.5 Percentage of participants |
| SFC 50/100 Mcg/Day | Percentage of Subjects With Rescue Medication-Free Nights and Days | After 4 Weeks of Treatment | 93.8 Percentage of participants |
| SLM 50 Mcg + FP 100 Mcg/Day | Percentage of Subjects With Rescue Medication-Free Nights and Days | Baseline | 87.5 Percentage of participants |
| SLM 50 Mcg + FP 100 Mcg/Day | Percentage of Subjects With Rescue Medication-Free Nights and Days | After 4 Weeks of Treatment | 87.5 Percentage of participants |
Secondary
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).
Time frame: Extension Period Weeks 11-30
Population: FAS (Full Analysis Set) during the Extension period: all subjects switched to Extension period and received GW815SF HFA MDI.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SFC 50/100 Mcg/Day | Percentage of Subjects With Rescue Medication-Free Nights & Days After 20 Weeks of Treatment | Baseline | 90.0 Percentage of participants |
| SFC 50/100 Mcg/Day | Percentage of Subjects With Rescue Medication-Free Nights & Days After 20 Weeks of Treatment | After 20 weeks of treatment (at week 30) | 89.1 Percentage of participants |
Secondary
Percentage of Subjects With Symptom-Free Nights & Days
Percentage of subjects with Symptom Free Nights & Days after 4 weeks of Treatment
Time frame: Crossover Period Week 1-4, 7-10
Population: PPS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SFC 50/100 Mcg/Day | Percentage of Subjects With Symptom-Free Nights & Days | Baseline | 72.9 Percent of participants |
| SFC 50/100 Mcg/Day | Percentage of Subjects With Symptom-Free Nights & Days | After 4 Weeks of Treatment | 91.7 Percent of participants |
| SLM 50 Mcg + FP 100 Mcg/Day | Percentage of Subjects With Symptom-Free Nights & Days | Baseline | 81.3 Percent of participants |
| SLM 50 Mcg + FP 100 Mcg/Day | Percentage of Subjects With Symptom-Free Nights & Days | After 4 Weeks of Treatment | 81.3 Percent of participants |
Secondary
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).
Time frame: Extension Period Weeks 11-30
Population: FAS (Full Analysis Set) during the Extension period: all subjects switched to Extension period and received GW815SF HFA MDI.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SFC 50/100 Mcg/Day | Percentage of Subjects With Symptom-Free Nights & Days After 20 Weeks of Treatment | Baseline | 84.0 Percentage of participants |
| SFC 50/100 Mcg/Day | Percentage of Subjects With Symptom-Free Nights & Days After 20 Weeks of Treatment | After 20 weeks of treatment (at week 30) | 84.8 Percentage of participants |