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

Study Overview
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Brief Summary
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The primary purpose of the study is to assess the safety and tolerability of 52-week teatment with fluticasone furoate/GW642444 inhalation powder once-daily and FF inhalation powder once-daily in Japanese adult subjects with asthma.

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

Conditions
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Asthma

Intervention / Treatment
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* Drug: Fluticasone Furoate/GW642444 Inhalation Powder
* Drug: Fluticasone Furoate Inhalation Powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Out patient at least 18 years of age Both genderds; females of childbearing potential must be willing to use birth control method A diagnosis of asthma at least 6 months prior to Screening A best FEV1 of at least 50% of the predicted nomal value at Screening Subjects have been receiving maintanance therapy for asthma, for at least 4 weeks prior to Screening Exclusion Criteria: History of life-threating asthma Respiratory infection or oral candidiasis Asthma exacerbation within 12 weeks Concurrent respiratory disease or other disease that would confound study participation or affect subject safety Allergies to study drugs, study drugs7 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: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluticasone Furoate/GW642444<br>Combination inhaled corticosteroid and long-acting beta2-agonist | Drug: Fluticasone Furoate/GW642444 Inhalation Powder<br>* Fluticasone Furoate/GW642444 inhalation powder inhaled orally once daily for 52 weeks<br>|
| Experimental: Fluticasone Furoate<br>Inhaled corticosteroid | Drug: Fluticasone Furoate Inhalation Powder<br>* Fluticasone Furoate 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) | 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. | 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 |
| --- | --- | --- |
| Laboratory Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, and Total Neutrophils at 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. | Baseline (Week -2), Week 12, Week 24, and Week 52/WD | 
| Laboratory Parameters of Eosinophils, Platelet Count, White Blood Cell (WBC), and Total Neutrophils at 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. | Baseline (Week -2), Week 12, Week 24, and Week 52/WD | 
| Laboratory Parameter of Hemoglobin at 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. | Baseline (Week -2), Week 12, Week 24, and Week 52/WD | 
| Laboratory Parameter of Hematocrit at 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. | Baseline (Week -2), Week 12, Week 24, and Week 52/WD | 
| Laboratory Parameter of Red Blood Cell Count at 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. | Baseline (Week -2), Week 12, Week 24, and Week 52/WD | 
| Laboratory Parameter of Albumin and Total Protein (TP) at 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. | Baseline (Week -2), Week 12, Week 24, and Week 52/WD | 
| Laboratory Parameter of Alkaline Phosphatase (AP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Creatine Kinase, Gamma Glutamyl Transferase (GGT), and Lactate Dehydrogenase (LDH) at BL (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. | Baseline (Week -2), Week 12, Week 24, and Week 52/WD | 
| Laboratory Parameter of Bilirubin (Direct [BD], Indirect [BI], Total [BT], Creatinine, and Uric Acid at 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. | Baseline (Week -2), Week 12, Week 24, and Week 52/WD | 
| Laboratory Parameter of Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at 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. | Baseline (Week -2), Week 12, Week 24, and Week 52/WD | 
| Laboratory Parameter of Urine Potential of Hydrogen (pH) at 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. | Baseline (Week -2), Week 12, Week 24, and Week 52/WD | 
| Laboratory Parameter of Urine Specific Gravity (USG) at 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. | Baseline (Week -2), Week 12, Week 24, and Week 52/WD | 
| Number of Participants for the Indicated Uninalysis Parameters Tested by Dipstick at Baseline (BL), 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. | Baseline (Week -2), Week 12, Week 24, and Week 52/WD | 
| Change From Baseline in the 24-hour Urinary Cortisol Excretion | 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. | Baseline (Week 0), Week 24, and Week 52/WD | 
| Change From Baseline in Blood Pressure | 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. | Baseline (Week 0), Week 12, Week 24, and Week 52/WD | 
| Change From Baseline in Heart Rate (HR) | 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. | Baseline (Week 0), Week 12, Week 24, and 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 (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. | Week 12, Week 24, and Week 52/WD | 
| Number of Participants With Severe Asthma Exacerbation During the Study Treatment | 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. | Baseline up to Week 52 | 
| Change From Baseline in Diary Data - Morning (AM) Peak Expiratory Flow (PEF) and Evening (PM) PEF During the Study Treatment | 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. | Baseline up to Week 52 | 
| Change From Baseline in Asthma Symptom Score During the Study Treatment | 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. | Baseline up to Week 52 | 
| Change From Baseline in the Percentage of Symptom-free 24-hour Periods During the Study Treatment | 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. | Baseline up to Week 52 | 
| Change From Baseline in the Percentage of Rescue-free 24-hour Periods | 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. | Baseline up to Week 52 | 
| Number of Rescue Medication Inhalations | 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). | Baseline up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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asthma, Fluticasone furoate, GW642444