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

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. Relatedness was assessed by the investigator.

Time frame: From the start of investigational product to the last dose of treatment (up to Week 52/Withdrawal [WD])

Population: ITT Population

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 SAEs.

Time frame: From the start of investigational product to the last dose of treatment (up to Week 52/Withdrawal [WD])

Population: Intent-to-Treat (ITT) Population: all participants who had been randomized to and received at least one dose of randomized medication in the treatment period

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 post-Baseline value minus the Baseline value.

Time frame: Baseline (Week 0), Week 24, and Week 52/Withdrawal (WD)

Population: The Urine Cortisol Population: all participants in the ITT Population for whom a urine sample was obtained and whose urine sample was not considered to have confounding factors that could affect the interpretation of the results. Only those participants with post-Baseline data available at the indicated time points were analyzed.

Blood pressure measurement included systolic blood pressure (SBP) and diastolic blood pressure (DBP) at Weeks 4, 8, 12, 16, 24, 32, 40, and 52; Week 24/WD; 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.

Time frame: Baseline (Week 0), Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 52, Week 24/WD, and Week 52/WD

Population: ITT Population. Only those participants with post-Baseline data available at the indicated time points were analyzed.

Heart rate was measured in a sitting position after a participant was kept at rest for at least 5 minutes at assessment time points (Weeks 4, 8, 12, 16, 24, 32, 40, and 52; Week 24/WD; and Week 52/WD). Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline (Week 0), Week 4, Week 8, Week 12, Week 16, Week 24, Week 32, Week 40, Week 52, Week 24/WD, Week 52/WD

Population: ITT Population. Only those participants with post-Baseline data available at the indicated time points were analyzed.

Clinical chemistry and urinalysis parameters included: Albumin, Alkaline Phosphatase (AP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Bilirubin (Direct \[BD\], Indirect \[BI\], and Total \[BT\]), Creatine Kinase (CK), Chloride, Carbon Dioxide content/Bicarbonate (CO2/BC), Creatinine, Gamma Glutamyl Transferase (GGT), Glucose, Potassium, Lactate Dehydrogenase (LDH), Sodium, Urine pH, Urine Specific Gravity (USG),Total Protein (TP), Urea/Blood urea nitrogen (BUN), and Uric Acid (UA). Data are reported as the number of participants who had low, normal, and high levels at BL (Week-2) and Week 52/WD.

Time frame: Baseline (Week -2), and Week 52/Withdrawal (WD

Population: ITT Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed.; thus the number of participants analyzed reflects everyone in the ITT Population. The number of participants assessed for each parameter is indicated by n=X, X.

Hematological parameters included: Basophils (Baso), Eosinophils (Eosin), Lymphocytes (Lymph), Monocytes (Mono), Total Neutrophils (TN), Hemoglobin (Hemo), Hematocrit (Hmcrt), Platelet Count (PT), Red Blood Cell Count (RBC Count), White Blood Cell Count (WBC Count). Data are reported as the number of participants who had low, normal, and high levels at BL (Week-2) and Week 52/WD.

Time frame: Baseline (Week -2), and Week 52/Withdrawal (WD)

Population: ITT Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed.; thus the number of participants analyzed reflects everyone in the ITT Population. The number of participants assessed for each parameter is indicated by n=X, X.

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, 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.

Time frame: Baseline (Week -2), Week 52/Withdrawal (WD)

Population: ITT Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed.; thus the number of participants analyzed reflects everyone in the ITT Population. The number of participants assessed for each parameter is indicated by n=X, X.

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 (Week 12, Week 24, and Week52). Data are presented for clinically significant (CS) as well as not clinically significant (NCS) abnormal findings. Any abnormal ECG, including those that worsen from baseline, and clinically significant as assessed by the investigator were recorded as CS.

Time frame: Baseline (Week -2), Week 12, Week 24, and Week 52

Population: ITT Population. Only participants remaining in the study and contributing evaluable data at the indicated time points were analyzed.; thus the number of participants analyzed reflects everyone in the ITT Population. The number of participants assessed for each parameter is indicated by n=X, X.

Pneumonia is an inflammatory condition of the lung, affecting primarily the microscopic air sacs known as alveoli. All diagnoses of pneumonia (radiographically confirmed or unconfirmed) were reported as an AE or SAE. 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 ot

Time frame: From the start of investigational product to the last dose of treatment (up to Week 52/Withdrawal [WD])

Population: ITT Population