The primary aim of this study is to clarify the position of FF and FF/Vilanterol (VI) 100/25 micrograms (mcg) compared with existing therapies by assessing FF dosage equivalent to low to middle-dose inhaled corticosteroids (ICS). The study is divided into Run-in period, Period 1 (open-label treatment), Period 2 (double blind treatment) and Follow-up. Subjects with well controlled asthma after completing a run-in period of 4 weeks will be switched from middle-dose ICS/long acting beta 2 agonist (LABA) equivalent dose to once-daily FF/VI 100/25 mcg for an 8 weeks treatment period (Period 1). After this, subjects will be randomized in a 1:1:1 ratio to receive either FP 250 mcg twice daily, FP 100 mcg twice daily or FF 100 mcg once daily in a 12 week double blind treatment period (Period 2). There will be a 1 week Follow-up Period following completion of the double-blind treatment period, or early withdrawal from the study. Overall , the total duration of subject's participation in the study will be for 25 weeks. RELVAR is a registered trademark of the GSK group of companies.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
430
FF/VI 100mg/25 mcg is available as a dry white powder to be given once daily in the evening via dry powder inhaler
FF 100 mcg is available as a dry white powder to be given once daily in the evening via dry powder inhaler
FP 250 mcg is available as a dry white powder to be given twice daily (morning and evening) via dry powder inhaler
FP 100 mcg is available as a dry white powder to be given twice daily (morning and evening) via dry powder inhaler
Matching placebo of Fluticasone Furoate will be given once daily in the evening via dry powder inhaler
Matching placebo of Fluticasone Propionate will be given twice daily (morning and evening) via dry powder inhaler
GSK Investigational Site
Aomori, Japan
GSK Investigational Site
Fukuoka, Japan
GSK Investigational Site
Fukuoka, Japan
GSK Investigational Site
Fukuoka, Japan
GSK Investigational Site
Fukuoka, Japan
GSK Investigational Site
Gifu, Japan
GSK Investigational Site
Hiroshima, Japan
GSK Investigational Site
Hyōgo, Japan
GSK Investigational Site
Ibaraki, Japan
GSK Investigational Site
Ibaraki, Japan
...and 23 more locations
Percentage of Participants (Par) Withdrawn From the Study Due to "Poorly-controlled Asthma" During Period 2
Asthma symptom scores (SS) were recorded by par using ratings 0 (no symptoms) to 5-symptoms so severe that par could not perform normal activity \[morning\] or to 4-symptoms so severe that par could not sleep at all \[nightly\]. Withdrawal due to poorly-controlled(WPC) (required step-up therapy) asthma was defined as asthma worsening/exacerbation or ≧3 per week of : day symptoms on ≧ 2 days, rescue use on ≧2 days, morning PEF \<80 % of best effort on ≧ 1 day, night symptoms on ≧1 or more day, a best pre-bronchodilator forced expiratory volume in 1s (FEV1) \< 80% at clinic . Percentage of par WPC asthma at visit 6, 7, 9 and 11 (Week 10, 12, 16 and 20 respectively) were reported. Cox Proportional Hazards Model was used with covariates of Baseline FEV1, gender, age and treatment group. Analysis was descriptive only, no p -values calculated, treatment differences and associated 95% CI were produced.
Time frame: From Week 9 to Week 20
Percentage of Participants With 'Well-controlled Asthma' at the End of Period 2
Asthma symptom scores(SS) were recorded by par using ratings 0 (no symptoms) to 5-symptoms so severe that par could not perform normal activity\[morning\] or to 4-symptoms so severe that par could not sleep at all\[nightly\]. "Well-controlled asthma" was defined as having no exacerbation/asthma worsening, no night-time symptoms, a best pre-bronchodilator forced expiratory volume in 1 second ≥80% at clinic, and ≥2 per week of: daytime symptoms on ≤1 day, rescue use on ≤1 day, or morning peak expiratory flow ≥80% of the best effort value. "Well-controlled asthma" at the end of period 2 was assessed in the week prior to Visit 11 (Week 20). Percentage of participants were calculated as the number of participants with "well-controlled asthma" divided by total number participants excluding withdrawals prior to visit 11 (end of period 2) other than asthma worsening/exacerbation. A Logistic Regression Model was used with covariates of Baseline FEV1, gender, age and treatment group.
Time frame: Week 20
Least Squares Mean Change From Baseline in Clinic Visit Trough FEV1 at the End of Period 2
FEV measures amount of air a person can exhale during a forced breath. The amount of air exhaled in one second of the forced breath is FEV1. Trough FEV1 was measured between 3pm and 11pm excluding Visit 1. Highest value from the three acceptable measurements were recorded. Change from Baseline was calculated as adjusted mean FEV1 value during Period 2 minus Baseline. The Baseline value was the predose value at the randomization (Visit 5: Week 8). Analysis of covariance (ANCOVA) Model was used with covariates of baseline FEV1, gender, age and treatment group. The adjusted mean from this model is presented \[least square mean (LSM)\].
Time frame: Week 20
Least Squares Mean Change From Baseline in Daily Morning (AM) and Evening (PM) PEF Averaged During Period 2
Peak expiratory flow is a person's maximum speed of expiration, as measured with a peak flow meter which determines person's ability to breathe out air. PEF was measured each morning and evening prior to study medication or any rescue salbutamol inhalation aerosol use, using an electronic peak flow meter. Mean change from Baseline was calculated as PEF value averaged during Period 2 (Week 9 to Week 20) minus Baseline. Data is presented separately for morning(AM) and evening(PM) assessments. The Baseline value was the mean of the daily values in one week prior to randomization (Visit 5: Week 8) separately for morning and evening. Adjusted mean change from baseline is presented \[least square mean (LSM)\].
Time frame: From Week 9 to Week 20
Least Squares Mean Change From Baseline in the Percentage of Symptom Free 24 Hour Periods During Period 2
Participants who were symptom free for 24-hours were assessed with the help of a daily Dairy. It included the details on daily asthma symptom scores ranging from 0 (no symptoms) to 5-symptoms so severe that participant could not perform normal activity \[morning\] or to 4-symptoms so severe that participants could not sleep at all \[nightly\]. Mean change from Baseline was calculated as percentage of symptom free 24 hours during Period 2 (Week 9 to Week 20) minus Baseline. The Baseline value was the mean of the daily values in one week prior to randomization (Visit 5: Week 8). Adjusted mean change from baseline is presented \[least square mean (LSM)\].
Time frame: From Week 9 to Week 20
Least Squares Mean Change From Baseline in the Percentage of Rescue Free 24 Hour (hr) Periods During Period 2
The time during which the participants did not have to take any rescue medication (medication intended to relieve symptoms immediately) was considered as a rescue free period. Participants who did not require inhalation of salbutamol (rescue medication) for 24-hours were captured with the help of a daily dairy, all participants were required to record use of rescue medication daily for day and night time separately on e-diary. Mean change from Baseline was calculated as percentage of rescue free 24 hour period during Period 2 (Week 9 to Week 20) minus Baseline value. The Baseline value was the mean of the daily values in one week prior to randomization (Visit 5: Week 8). Adjusted mean change from baseline is presented \[least square mean (LSM)\].
Time frame: From Week 9 to Week 20
Least Squares Mean Change From Baseline in Asthma Control Test (ACT) Score at the End of Period 2
The total ACT score is the sum of the scores attributed to the five questions, ranging from 5 (poor control of asthma) to 25 (complete control of asthma), with higher scores reflecting greater asthma control. An ACT score \>=20 indicates well-controlled asthma. The questions were designed to be self-completed by the participant. Mean change from Baseline was calculated as ACT score at the end of Period 2 (Week 20) minus Baseline value. The Baseline value was the predose value at randomization (Visit 5: Week 8). Adjusted mean change from baseline is presented \[least square mean(LSM)\].
Time frame: Week 20
Proportion of Subjects With ACT Score >= 20 at Visit 11 (Week 20)
Asthma control test is a five item questionnaire with each response rating from 1 to 5 (1 is severe and 5 is no event) of asthma events over previous 4-weeks. The questions were designed to be self-completed by the participant. The percentage of participants with ACT score \>=20 at the end of the Period 2 were analyzed using a logistic regression model including covariates for baseline ACT score, gender, age and treatment group.
Time frame: Week 20
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