Trial Outcomes & Findings for A Long-term Safety Study of Fluticasone Furoate (FF)/GW642444 and FF in Japanese Subjects With Asthma (NCT NCT01244984)

Following screening (Visit1) and a 2-week Run-in Period during which participants continued to use their respective asthma therapy at a fixed dose. Participants who met continuation criteria at the end of Run-in Period (Visit 2) were allocated to a 52-Week Treatment Period.

A Long-term Safety Study of Fluticasone Furoate (FF)/GW642444 and FF in Japanese Subjects With Asthma

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury. Refer to the general AE/SAE module for a list of AEs (occurring at a frequency threshold \>=5%) and SAE.

Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

Blood samples were collected for measurement at the following scheduled time points: Baseline (BL) (Week -2), Week 12, Week 24 and Week 52/WD.

Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

Blood samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

Urine samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

Urine samples were collected for measurement at the following scheduled time points: Baseline (Week -2), Week 12, Week 24 and Week 52/WD.

Urinalysis parameters included: Urine Occult Blood (UOB), Urine Glucose (UG), Urine Ketones (UK), Urine Protein (UP), and Urine Leukocyte Esterase test for detecting White Blood Cell (UWBC). The dipstick was a strip used to detect the presence or absence of these parameters in the urine sample. The dipstick test gives results in a semi-quantitative manner, and results can be read as negative (Neg), Trace (TRA), 1+, 2+, and 3+, indicating proportional concentrations in the urine sample. Data are reported as the number of participants who had neg, trace, 1+, 2+, and 3+ levels at Baseline (Week -2) and Week 52/WD.

Urine samples were collected for measurement of urinary cortisol excretion at the following scheduled time points: Baseline (Week 0), Week 24, and Week 52/WD. The 24-hour urinary cortisol excretion was calculated by multiplying the total volume of urine by the concentration of urinary cortisol. Cortisol is a hormone released from the adrenal gland that helps in fat, protein, and carbohydrate metabolism. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline.

Blood pressure measurement included systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Baseline (Week 0), Weeks 12, 24 and Week 52/WD. Blood pressure was measured in a sitting position after a participant was kept at rest for at least 5 minutes. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Heart rate was measured in a sitting position after a participant was kept at rest for at least 5 minutes at Baseline (Week 0), Weeks 12, 24 and Week 52/WD. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

A 12-lead ECG was recorded in a supine position after the participant was kept at rest in this position for at least 5 minutes at assessment time points (Baseline\[Week -2\], Week 12, 24 and Week 52/WD) in the treatment period. Data are presented for clinically significant (CS) as well as not clinically significant (NCS) abnormal (Abn) findings. Any abnormal ECG, including those that worsen from Baseline, and determined clinically significant by the assessment of the investigator were recorded as CS.

A severe asthma exacerbation is defined as the deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. Courses of corticosteroids separated by 1 week or more were treated as separate severe exacerbations.

Change from Baseline in AM and PM PEF at 52 weeks of evaluation period during study treatment was recorded in the dairy record card. The Baseline value was calculated as the mean of all available data recorded during the7 days immediately prior to the treatment start date (including Day 1: Day 1 is treatment start date). The PEF is defined as the greatest rate of airflow that can be achieved during forced exhalation beginning with the lungs fully inflated.

The Baseline value was calculated as the mean of all available data recorded during the 7 days immediately prior to Visit 2 (treatment assignment visit). Participants entered their asthma symptom score in the patient diary twice daily (morning and evening). Daytime asthma symptom scores: 0-no asthma symptoms, 1-one episode of short-time asthma symptoms, 2-two or more episodes of short-time asthma symptoms, 3-asthma symptoms occurring during most part of daytime without interference with daily life activities, 4-asthma symptoms occurring during most part of daytime with interference with daily life activities, 5-severe asthma symptoms that disable working or daily life activities. Nighttime asthma symptom scores: 0-no asthma symptoms, 1-one awakening due to asthma symptoms, 2-two or more awakenings due to asthma symptoms, 3-asthma symptoms almost prevented the participant from sleeping, 4-severe asthma symptoms completely prevented from sleeping.

Participants who were symptom free for 24-hours were assessed. Change from Baseline is calculated as the value at Week 52 minus the value at Baseline.

The time span 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. Change from Baseline is calculated as the value at Week 52 minus the value at Baseline.

Salbutamol inhaler was used as the rescue medication. Participants entered the number of rescue medication inhalations in the patient diary twice daily (morning and evening).