Study to Evaluate the Safety and Efficacy of Formoterol in a Daily Dose of 18 µg (9 µg Twice Daily) in Japanese Chronic Obstructive Pulmonary Disease (COPD) Patients

Study Overview
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Brief Summary
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This study is a multicentre, open, randomised, parallel-group study with formoterol 9 μg one inhalation b.i.d, or standard COPD therapy. Standard (reference) COPD treatment arm should be the group to refer to when safety results of formoterol arm will be evaluated. 240 patients with moderate-to-severe COPD will be randomised (120 patients in the formoterol-arm and 120 patients on standard COPD therapy).

Official Title
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An Open Phase III, Multi-centre 52-week, Parallel-group Study Evaluating the Safety and Efficacy of Formoterol 18 μg Daily Dose Compared With Standard COPD 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: Formoterol (OT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients, men or women ≥ 40 years A clinical diagnosis of COPD according to guidelines, and current COPD symptoms. Post-bronchodilator FEV1 < 80% of predicted normal value and FEV1/FVC < 70%, post-bronchodilator Exclusion Criteria: A history and/or current clinical diagnosis of asthma and atopic diseases such as Allergic rhinitis Patients who have experienced COPD exacerbation requiring at least one of the following treatment, hospitalisation and/or a course of systemic steroid within 4 weeks prior to the study start. Significant or unstable ischaemic heart disease, arrhythmia, cardiomyopathy, heart failure, uncontrolled hypertension as defined by the investigator, or any other relevant cardiovascular disorder as judged by the investigator

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>Formoterol 9 μg/dose | Drug: Formoterol (OT)<br>* 9 μg/dose, Inhaled, twice daily for 52 weeks<br>* Other names: Oxis Turbuhaler®;|

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 week 52 | 
| Clinical Laboratory Test: Haematology -Haemoglobin | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Haematology-Leucocytes | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Haematology-Platelet Count | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Haematology Eosinophils | Change from baseline | baseline and week 52 | 
| Clinical Laboratory Test: Haematology Basophil | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Haematology-Lymphocytes | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Haematology-Monocytes | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Haematology -Neutrophils | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Clinical Chemistry- S-Alanine Aminotransferase | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Clinical Chemistry-S-Aspartate Aminotransferase | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Clinical Chemistry-S-Alkaline Phosphatase (ALP) | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Clinical Chemistry-S-Creatinine | Change from Baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Clinical Chemistry-S-Total Bilirubin | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Clinical Chemistry-S-Sodium | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Clinical Chemistry-S-Potassium | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Clinical Chemistry-S- Calcium | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Clinical Chemistry-S-Albumin | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Clinical Chemistry-S-Total Protein | Change from baseline | Baseline and week 52 | 
| Clinical Laboratory Test: Clinical Chemistry - S-Blood Urea Nitrogen (BUN) | Change from baseline | Baseline and week 52 | 
| Vital Signs- Sitting SBP | Change from baseline | Baseline and week 52 | 
| Vital Signs- Sitting DBP | Change from baseline | Baseline and week 52 | 
| Vital Signs - Pulse Rate | Change from baseline | Baseline and week 52 | 
| ECG Variables - Heart Rate | Change from baseline | Baseline and week 52 | 
| ECG Variables - QT Interval | Change from baseline | Baseline and week 52 | 
| ECG Variables - QTcB Interval | Change from baseline | Baseline and week 52 | 
| ECG Variables QTcF Interval | Change from baseline | Baseline and week 52 | 
| ECG Variables RR Interval | Change from baseline | Baseline and week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced Expiratory Volume in One Second (FEV1) | The ratio of the average value of available data for mean from Weeks 0, 4, 8, 17, 26, 34, 43 and 52 to the baseline for each treatment group | Before randomization, 0, 4, 8, 17, 26, 34, 43 and 52 weeks after randomization | 
| Forced Vital Capacity (FVC) | 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 | Before randomization, 0, 4, 8, 17, 26, 34, 43 and 52 weeks after randomization | 
| Morning Peak Expiratory Flow(PEF) | The change from Run-in period average to Treatment period average for each treatment group | Daily during run-in period (14 - 18 days before Randomisation visit)and daily during 52-week randomization treatment | 
| Evening Peak Expiratory Flow (PEF) | The change from Run-in period average to Treatment period average for each treatment group | Daily during run-in period (14 - 18 days before Randomisation visit) and daily during 52-week randomization treatment | 
| Night-time Awakening Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | There are 5 alternatives (scored 0 to 4, with 4 being the most severe condition). The change from Run-in period average to Treatment period average for each treatment group | Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment | 
| Daytime Breathlessness Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | There are 5 alternatives (scored 0 to 4, with 4 being the most severe condition). The change from Run-in period average to Treatment period average for each treatment group | Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment | 
| Daytime Cough Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | There are 5 alternatives (scored 0 to 4, with 4 being the most severe condition). The change from Run-in period average to Treatment period average for each treatment group | Daily during run-in period (14 - 18 days before Randomisation visit) and daily during 52-week randomization treatment | 
| Total Chronic Obstructive Pulmonary Disease (COPD) Symptom Score | The Total COPD Symptom score is the sum of the measures night-time awakening, breathlessness and cough, ranges from 0 to 12 with 12 being the most severe. The change from Run-in period average to Treatment period average for each treatment group. | Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment | 
| Number of COPD Exacerbations Over the 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 was presented here. | Daily during 52-week randomization treatment | 
| Use of SABA (Salbutamol) as Reliever Medication | The change from Run-in period average to Treatment period average for each treatment group. | Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment | 
| St George's Respiratory Questionnaire (SGRQ) Total Score | SGRQ total score shows the impact of COPD on patient's health status, and expressed as a percentage of impairment with scale from 0 (best health status) to 100 (worst possible status). A negative rate of decline shows decreasing SGRQ total score (or improved health) over time, while a positive value shows increasing score (or worsen health). The change from Run-in period average to Treatment period average for each treatment group | Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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OT, Chronic Obstructive Pulmonary Disease, COPD, Japanese, Phase 3, Safety, Oxis