Long-term Safety Study for GSK573719 in Japanese

Study Overview
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Brief Summary
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The objective of this study is to evaluate the safety and tolerability of GSK573719 Inhalation Powder 125 mcg once-daily over 52 weeks in Japanese subjects with COPD.

Detailed Description
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Chronic Obstructive Pulmonary Disease (COPD) treatment guidelines recommend an incremental approach to pharmacological treatment as the disease state worsens, involving the use of combinations of drug classes with different or complementary mechanisms of action [Celli, 2004, GOLD 2009]. As disease progresses from mild to moderate, regular treatment with one or more long-acting bronchodilators is recommended. Inhaled bronchodilators, including beta2 agonists and anticholinergics are included with inhaled corticosteroids (ICS) therapy and are mainstays of therapy in patients diagnosed with COPD. Since GSK573719 Inhalation Powder is expected to be used for chronic management of COPD as long-acting muscarinic antagonist (LAMA), this study is intended to evaluate the safety and tolerability of long-term administration of GSK573719 Inhalation Powder 125 mcg in Japanese patients with COPD at doses possibly used to be in Japan. In this study, patient safety will also be monitored by evaluating pulmonary function and clinical symptoms.

Official Title
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A 52-week, Multi-centre, Open-label Study to Evaluate the Safety and Tolerability of GSK573719 125 mcg Once-daily Via Novel Dry Powder Inhaler (nDPI) in Japanese Subjects With Chronic Obstructive Pulmonary Disease.

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: GSK573719


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatient. A signed and dated written informed consent prior to study participation. Japanese subjects 40 years of age or older at Visit 1. Male or female subjects. A female is eligible if she is of: Non-child bearing potential or Child bearing potential agrees to one of the contraceptive methods. Subjects with a clinical history of COPD in accordance with the definition by COPD domestic guideline. Current or former cigarette smokers with a history of cigarette smoking of >=10 pack-years at Visit 1. Subject with a measured post-salbutamol forced expiratory volume/forced vital capacity (FEV1/FVC) ratio of <70% and Subjects with a measured post-salbutamol FEV1 <80% of predicted normal values. Exclusion Criteria (Visit 1): Women who are pregnant or lactating or are planning on becoming pregnant during the study. A current diagnosis of asthma. Known respiratory disorders other than COPD. Subjects with historical or current evidence of clinically significant abnormalities that are uncontrolled. A chest X-ray or computed tomography (CT) scan that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD. Allergy or hypersensitivity to muscarinic, beta2-agonist, lactose/milk protein or magnesium stearate or a condition that contraindicates participation. Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1. Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1). An abnormal and significant ECG finding from the 12-lead ECG conducted at Visit 1. Significantly abnormal finding from clinical chemistry or hematology, tests at Visit 1. Use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed for greater than 12 hours a day. Regular use (prescribed every day, not for as-needed use) of short-acting bronchodilators (e.g., salbutamol) via nebulized therapy. Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1. Affiliation with Investigator Site. Previous use of GSK573719, the GSK573719/GW642444 combination. Use of any other investigational medication within 30 days or 5 drug half-lives (whichever is longer). Exclusion Criteria (Visit 2): - COPD Exacerbation during run-in period: Subject must not have experienced a COPD exacerbation or a lower respiratory tract infection during run-in or at Visit 2.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK573719<br>125mcg | Drug: GSK573719<br>* GSK573719 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 Adverse Event (AE) or Any Serious Adverse Event (SAE) Throughout the Treatment Period | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of the study medication, whether or not considered related to the study medication. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the study medication. 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 or incapacity, or is a congenital anomaly or birth defect, or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, or is an event of possible drug-induced liver injury. Medical or scientific judgment was exercised in deciding whether reporting was appropriate in other situations. | From the first dose of study medication up to 52 weeks | 
| Number of Participants With AEs Classified by the Indicated Maximum Grade Severity Throughout the Treatment Period | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of the study medication, whether or not considered related to the study medication. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the study medication. AEs were classified according to intensity based upon the investigators' clinical judgment. The intensity was categorized as: mild (an event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities); moderate (an event that is sufficiently discomforting to interfere with normal everyday activities); or severe (an event that prevents normal everyday activities). | From the first dose of study medication up to 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Basophil, Eosinophil, Lymphocyte, Monocyte, and Total Neutrophil Values at Baseline (BL) (Week -2), Week 12, Week 24, Week 36, Week 52, the Withdrawal (WD) Visit, Week 24/WD, and Week 52/WD | Blood samples were collected for the measurement of the indicated laboratory parameters at the following time points: BL (Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit (conducted for participants who withdrew at any point during the study), Week 24/WD Visit (conducted for participants who completed the Week 24 Visit or withdrew before Week 24), and Week 52/WD Visit (conducted for participants who completed the Week 52 Visit or withdrew before Week 52). The BL value for clinical laboratory tests was the value recorded on Week -2 (Screening Visit). | BL (Screening Visit: Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD Visit, and Week 52/WD Visit | 
| Eosinophil Values, Total Neutrophil Values, Platelet Count, and White Blood Cell (WBC) Count at BL (Week -2), Week 12, Week 24, Week 36, Week 52, the Withdrawal (WD) Visit, Week 24/WD, and Week 52/WD | Blood samples were collected for the measurement of the indicated laboratory parameters at the following time points: BL (Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit (conducted for participants who withdrew at any point during the study), Week 24/WD (conducted for participants who completed the Week 24 Visit or withdrew before Week 24), and Week 52/WD (conducted for participants who completed the Week 52 Visit or withdrew before Week 52). The BL value for clinical laboratory tests was the value recorded on Week -2 (Screening Visit). | BL (Screening Visit: Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD | 
| Hemoglobin, Albumin, and Total Protein Values at BL (Week -2), Week 12, Week 24, Week 36, Week 52, the Withdrawal (WD) Visit, Week 24/WD, and Week 52/WD | Blood samples were collected for the measurement of the indicated laboratory parameters at the following time points: BL (Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit (conducted for participants who withdrew at any point during the study), Week 24/WD (conducted for participants who completed the Week 24 Visit or withdrew before Week 24), and Week 52/WD (conducted for participants who completed the Week 52 Visit or withdrew before Week 52). The BL value for clinical laboratory tests was the value recorded on Week -2 (Screening Visit). | BL (Screening Visit: Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD | 
| Hematocrit Values at BL (Week -2), Week 12, Week 24, Week 36, Week 52, the Withdrawal (WD) Visit, Week 24/WD, and Week 52/WD | Blood samples were collected for the measurement of hematocrit at the following time points: BL (Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit (conducted for participants who withdrew at any point during the study), Week 24/WD (conducted for participants who completed the Week 24 Visit or withdrew before Week 24), and Week 52/WD (conducted for participants who completed the Week 52 Visit or withdrew before Week 52). The BL value for clinical laboratory tests was the value recorded on Week -2 (Screening Visit). | BL (Screening Visit: Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD | 
| Alkaline Phosphatase (AP), Alanine Amino Transferase (ALT), Aspartate Amino Transferase (AST), Creatine Kinase, and Gamma Glutamyl Transferase (GGT) Values at BL (Week -2), Week 12, Week 24, Week 36, Week 52, the WD Visit, Week 24/WD, and Week 52/WD | Blood samples were collected for the measurement of the indicated laboratory parameters at the following time points: BL (Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit (conducted for participants who withdrew at any point during the study), Week 24/WD (conducted for participants who completed the Week 24 Visit or withdrew before Week 24), and Week 52/WD (conducted for participants who completed the Week 52 Visit or withdrew before Week 52). The BL value for clinical laboratory tests was the value recorded on Week -2 (Screening Visit). | BL (Screening Visit: Week -2), Week 12, Week 24, Week36, Week 52, WD Visit, Week 24/WD, and Week 52/WD | 
| Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Creatinine, and Uric Acid Values at BL (Week -2), Week 12, Week 24, Week 36, Week 52, the WD Visit, Week 24/WD, and Week 52/WD | Blood samples were collected for the measurement of the indicated laboratory parameters at the following time points: BL (Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit (conducted for participants who withdrew at any point during the study), Week 24/WD (conducted for participants who completed the Week 24 Visit or withdrew before Week 24), and Week 52/WD (conducted for participants who completed the Week 52 Visit or withdrew before Week 52). The BL value for clinical laboratory tests was the value recorded on Week -2 (Screening Visit). | BL (Screening Visit: Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD | 
| Calcium, Chloride, Glucose, Carbon Dioxide/Bicarbonate (CO2/HCO3), Potassium, Sodium, Inorganic Phosphorus, and Urea/Blood Urea Nitrogen (Urea/BUN) Values at BL (Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD | Blood samples were collected for the measurement of the indicated laboratory parameters at the following time points: BL (Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit (conducted for participants who withdrew at any point during the study), Week 24/WD (conducted for participants who completed the Week 24 Visit or withdrew before Week 24), and Week 52/WD (conducted for participants who completed the Week 52 Visit or withdrew before Week 52). The Baseline value for clinical laboratory tests was the value recorded on Week -2 (Screening Visit). | BL (Screening Visit: Week -2), Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD, and Week 52/WD | 
| Change From BL in Blood Pressure Throughout the Treatment Period | Blood pressure measurements included systolic blood pressure (SBP) and diastolic blood pressure (DBP). Blood pressure was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Change from BL was calculated as the assessment value at the time of interest minus the BL value. The BL value was recorded at Week 0. The WD Visit was conducted for participants who withdrew at any point during the study. The Week 24/WD Visit was conducted for participants who completed the Week 24 Visit or withdrew before Week 24. The Week 52/WD Visit was conducted for participants who completed the Week 52 Visit or withdrew before Week 52. | BL(Week 0), Week 4, Week 8, Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD Visit, and Week 52/WD Visit | 
| Change From BL in Heart Rate Throughout the Treatment Period | Heart rate was measured in a sitting position after the participant was kept at rest for at least 5 minutes. Change from BL was calculated as the assessment value at the time of interest minus the BL value. The BL value was recorded at Week 0. The WD Visit was conducted for participants who withdrew at any point during the study. The Week 24/WD Visit was conducted for participants who completed the Week 24 Visit or withdrew before Week 24. The Week 52/WD Visit was conducted for participants who completed the Week 52 Visit or withdrew before Week 52. | BL (Week 0), Week 4, Week 8, Week 12, Week 24, Week 36, Week 52, WD Visit, Week 24/WD Visit, and Week 52/WD Visit | 
| Number of Participants With Abnormal Findings in 12-lead Electrocardiograms (ECG) at the Indicated Time Points | 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. Data are presented as clinically significant (CS) or not clinically significant (NCS) abnormal findings. An abnormal and significant ECG finding includes the presence of a QT interval corrected for heart rate (QTc interval) >500 milliseconds (msec) or an uncorrected QT interval >600 msec, for participants with Bundle Branch Block QTc >530 msec based on an average QTc value of triplicate ECGs. The study investigator determined if the abnormal ECG finding was CS or NCS. The WD Visit was conducted for participants who withdrew at any point during the study. The Week 24/WD and Week 52/WD Visits were conducted for participants who completed the Week 24 Visit or withdrew before Week 24 and completed the Week 52 Visit or withdrew before Week 52, respectively. The BL value for clinical laboratory tests was the value recorded on Week -2 (Screening Visit). | BL (Screening Visit: Week -2), Week 12, Week 24,Week 36, Week 52, WD Visit, Week 24/WD Visit, and Week 52/WD Visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Obstructive Pulmonary Disease (COPD), GSK573719, Pharmacogenetics