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

Study Overview
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Brief Summary
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The primary purpose of the study is to evaluate the safety and tolerability of fluticasone furoate/GW642444 inhalation powder when administered once-daily for 52 weeks in Japanese patients with COPD.

Official Title
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A Long-term Study to Evaluate the Safety and Tolerability of Fluticasone Furoate (FF)/GW642444 Inhalation Powder in Japanese Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Fluticasone Furoate/GW642444 Inhalation Powder 100/25mcg
* Drug: Fluticasone Furoate/GW642444 Inhalation Powder 200/25mcg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Out patient at least 40 years of age Both genders; females childbearing potencial must be willing to use birth control method A diagnosis of COPD at Screening Subjects with a current or prior history of at least 10 pack-years of cigarett smoking at Screening Post-bronchodilator FEV1/FVC ratio of less than 70% Post-bronchodilator FEV1 of less than 80% Exclusion Criteria: Current diagnosis of sthma Respiratory disorders other than COPD Upper or lower respiratory infection, or exacerbation of COPD within 4 weeka prior to Screening Concurrent other disease that would confound study participation or affect subject safety Allergies to study drugs, study drugs' excipients, medications related to study drugs Taking another investigational medication or medication prohibited for use during this study

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluticasone Furoate/GW642444 100/25mcg<br>Combination inhaled corticosteroid and long-acting beta2-agonist | Drug: Fluticasone Furoate/GW642444 Inhalation Powder 100/25mcg<br>* Fluticasone furoate/GW642444 inhalation powder inhaled orally once daily for 52 weeks<br>|
| Experimental: Fluticasone Furoate/GW642444 200/25mcg<br>Combination inhaled corticosteroid and long-acting beta2-agonist | Drug: Fluticasone Furoate/GW642444 Inhalation Powder 200/25mcg<br>* Fluticasone furoate/GW642444 inhalation powder inhaled orally once daily for 52 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious Adverse Event (SAE) Throughout the Treatment Period | 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. | From the start of investigational product to the last dose of treatment (up to Week 52/Withdrawal [WD]) | 
| Number of Participants With Any Drug-related AE and Any Drug-related SAE Throughout the Treatment Period | 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. | From the start of investigational product to the last dose of treatment (up to Week 52/Withdrawal [WD]) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Pneumonia During the Treatment Period | 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 | From the start of investigational product to the last dose of treatment (up to Week 52/Withdrawal [WD]) | 
| Number of Participants for the Indicated Hematological Parameters Who Experienced Low, Normal, and High Levels at Baseline (BL) and Week 52/Withdrawal (WD) | 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. | Baseline (Week -2), and Week 52/Withdrawal (WD) | 
| Number of Participants for the Indicated Clinical Chemistry and Urinalysis Parameters Who Experienced a Low, Normal, and High Levels at Baseline (BL) and Week 52/Withdrawal (WD) | 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. | Baseline (Week -2), and Week 52/Withdrawal (WD | 
| Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick at Baseline (BL) and Week 52/Withdrawal (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, 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. | Baseline (Week -2), Week 52/Withdrawal (WD) | 
| Change From Baseline in 24-hour Urinary Cortisol Excretion at Weeks 24 and 52/Withdrawal (WD) | 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. | Baseline (Week 0), Week 24, and Week 52/Withdrawal (WD) | 
| Change From Baseline in Blood Pressure at Weeks 4, 8, 12, 16, 24, 32, 40, and 52; Week 24/WD; and Week 52/WD | 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. | 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 | 
| Change From Baseline in Heart Rate (HR) at Weeks 4, 8, 12, 16, 24, 32, 40, and 52; Week 24/WD; and Week 52/WD | 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. | 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 | 
| Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings | 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. | Baseline (Week -2), Week 12, Week 24, and Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GW642444, COPD, Fluticasone Furoate