A Safety and Efficacy Study of Symbicort Turbuhaler Compared With Standard Chronic Obstructive Pulmonary Disease (COPD) Treatment in Japan

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of Symbicort Turbuhaler compared to standard COPD treatment during one year in Japanese patients with COPD.

Official Title
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An Open-label Phase III, Multi-centre 52-week , Parallel-group Study Evaluating the Safety and Efficacy of Symbicort Turbuhaler 320/9 Twice Daily Compared With Standard Treatment in Japanese Patients With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Symbicort Turbuhaler (Budesonide/formoterol)
* Drug: Drug: any available COPD treatment; investigator to decide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A current clinical diagnosis of COPD according to the guidelines (GOLD, JPS) Documented COPD symptoms for more than 2 years Pre-bronchodilator FEV1≦50% of predicted normal value, and post-bronchodilator FEV1/FVC<70% Exclusion Criteria: History and/or current clinical diagnosis of asthma and atopic diseases such as allergic rhinitis Subjects with significant or unstable ischemic heart disease, arrhythmia, cardiomyopathy, heart failure, uncontrolled hypertension as defined by the investigator, or any other relevant cardiovascular disorder as judged by the investigator COPD exacerbation during the run-in period or within 4 weeks prior to registration, requiring hospitalization and/or treatment with systemic steroids.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Symbicort Turbuhaler (Budesonide/formoterol)<br>* 2 x 160/4.5 microgram, inhalation, bid, 52 weeks<br>* Other names: Symbicort Turbuhaler;|
| Active Comparator: 2<br> | Drug: Drug: any available COPD treatment; investigator to decide<br>* According to investigator decision, 52 weeks, Standard COPD treatment according to investigator decision<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Laboratory Test: Haematology -Erythrocytes | Mean change from Baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Haematology -Haemoglobin | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Haematology -Leucocytes | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Haematology -Platelet Count | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Haematology -Eosinophils | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Haematology -Basophils | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Haematology -Lymphocytes | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Haematology -Monocytes | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Haematology -Neutrophils | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Clinical Chemistry- S-Alanine Aminotransferase | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Clinical Chemistry- S-Aspartate Aminotransferase | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Clinical Chemistry- S-Alkaline Phosphatase (ALP) | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Clinical Chemistry- S-Creatinine | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Clinical Chemistry- S-Total Bilirubin | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Clinical Chemistry- S-Sodium | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Clinical Chemistry- S-Potassium | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Clinical Chemistry- S- Calcium | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Clinical Chemistry- S-Albumin | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Clinical Chemistry- S-Protein, Total | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Clinical Chemistry- S-C-Reactive Protein | Change from baseline | Baseline and 52 week after | 
| Clinical Laboratory Test: Clinical Chemistry- S-Urea Nitrogen | Change from baseline | Baseline and 52 week after | 
| Vital Signs- Sitting Systolic Blood Pressure(SBP) | Change from baseline | Baseline and 52 week after | 
| Vital Signs- Sitting Diastolic Blood Pressure(DBP) | Change from baseline | Baseline and 52 week after | 
| Vital Signs- Pulse Rate | Change from baseline | Baseline and 52 week after | 
| ECG Variables - Heart Rate | Change from baseline | Baseline and 52 week after | 
| ECG Variables - QT Interval | Change from baseline | Baseline and 52 week after | 
| ECG Variables - QTcB Interval | Change from baseline | Baseline and 52 week after | 
| ECG Variables - QTcF Interval | Change from baseline | Baseline and 52 week after | 
| ECG Variables - RR Interval | Change from baseline | Baseline and 52 week after | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic Obstructive Pulmonary Disease (COPD) symptoms_Night-time Awakening | There are 5 alternatives (scored 0 to 4, 0= no awakening and 4 =did not sleep at all). The change from Run-in period average to Treatment period average for each treatment group | Daily during run-in period and daily during 52-week randomization treatment | 
| Chronic Obstructive Pulmonary Disease (COPD) symptoms_Breathlessness | There are 5 alternatives (scored 0 to 4, 0= unaware of any difficulty and 4 =almost constant, present even when resting). The change from Run-in period average to Treatment period average for each treatment group | Daily during run-in period and daily during 52-week randomization treatment | 
| Chronic Obstructive Pulmonary Disease (COPD) symptoms_cough | There are 5 alternatives (scored 0 to 4, 0= unaware of coughing, 4= never free of cough or need to cough). The change from Run-in period average to Treatment period average for each treatment group | Daily during run-in period and daily during 52-week randomization treatment | 
| Forced Expiratory Volume in 1 Second (FEV1) Measured With the Spirometer at the Clinic | The ratio of the average value of available data for Weeks 0, 4, 8, 17, 26, 34, 43 and 52 to the baseline for each treatment group. Ratio is being reported as a percentage in this Measure. | Before randomization, 0, 4, 8, 17, 26, 34, 43 and 52 weeks after randomization | 
| Forced Vital Capacity (FVC) Measured With the Spirometer at the Clinic | The ratio of the average value of available data for Weeks 0, 4, 8, 17, 26, 34, 43 and 52 to the baseline for each treatment group. Ratio is being reported as a percentage in this Measure. | Before randomization, 0, 4, 8, 17, 26, 34, 43 and 52 weeks after randomization | 
| Time to First COPD Exacerbation | A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. The percentage of participants who had experienced COPD exacerbation at the end of the study for each treatment group. | Daily during 52-week randomization treatment | 
| Number of COPD Exacerbations Over the Study Treatment Period | A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as worsening in COPD symptoms requiring treatment with either a course of systemic steroid or hospitalisation. Number of COPD exacerbation during 52-week randomization treatment | Daily during 52-week randomization treatment | 
| Rescue Medication Use | The change from run-in period and daily during 52-week randomization treatment | Daily during 52-week randomization treatment | 
| Health Related Quality of Life (HRQL) Based on the St. George's Respiratory Questionnaire (SGRQ) | The change from run-in period and daily during 52-week randomization treatment average for each treatment group. The SGRQ ranges from 0 (no impairment of quality of life) to 100 (highest impairment of quality of life). | Daily during run-in period and daily 52-week randomization treatment | 
| Morning Peak Expiratory Flow (PEF) Measured at Home | The change from Run-in period average to 52-week randomization Treatment period average for each treatment group | Daily during run-in period and daily 52-week randomization treatment | 
| Evening Peak Expiratory Flow (PEF) Measured at Home | The change from Run-in period average to 52-week randomization Treatment period average for each treatment group | Daily during run-in period and daily 52-week randomization treatment | 
| Morning FEV1 Measured by the Subjects at Home | The change from run-in period and daily during 52-week randomization treatment | Daily during run-in period and daily 52-week randomization treatment | 
| Evening FEV1 Measured by the Subjects at Home | The change from run-in period and daily during 52-week randomization treatment | Daily during run-in period and daily 52-week randomization treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Symbicort, Safety, Efficacy, COPD, Japanese