Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Chronic Obstructive Pulmonary Disease, COPD, Japanese, Phase 3, Safety, OT, Oxis
Brief summary
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).
Interventions
DRUGFormoterol (OT)
9 μg/dose, Inhaled, twice daily for 52 weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ECG Variables RR Interval | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Clinical Chemistry-S-Potassium | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Clinical Chemistry-S- Calcium | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Clinical Chemistry-S-Albumin | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Clinical Chemistry-S-Total Protein | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Clinical Chemistry - S-Blood Urea Nitrogen (BUN) | Baseline and week 52 | Change from baseline |
| Vital Signs- Sitting SBP | Baseline and week 52 | Change from baseline |
| Vital Signs- Sitting DBP | Baseline and week 52 | Change from baseline |
| Vital Signs - Pulse Rate | Baseline and week 52 | Change from baseline |
| ECG Variables - Heart Rate | Baseline and week 52 | Change from baseline |
| ECG Variables - QT Interval | Baseline and week 52 | Change from baseline |
| ECG Variables - QTcB Interval | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Haematology -Erythrocytes | Baseline and week 52 | Mean change from Baseline |
| Clinical Laboratory Test: Haematology -Haemoglobin | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Haematology-Leucocytes | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Haematology-Platelet Count | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Haematology Eosinophils | baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Haematology Basophil | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Haematology-Lymphocytes | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Haematology-Monocytes | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Haematology -Neutrophils | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Clinical Chemistry- S-Alanine Aminotransferase | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Clinical Chemistry-S-Aspartate Aminotransferase | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Clinical Chemistry-S-Alkaline Phosphatase (ALP) | Baseline and week 52 | Change from baseline |
| ECG Variables QTcF Interval | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Clinical Chemistry-S-Creatinine | Baseline and week 52 | Change from Baseline |
| Clinical Laboratory Test: Clinical Chemistry-S-Total Bilirubin | Baseline and week 52 | Change from baseline |
| Clinical Laboratory Test: Clinical Chemistry-S-Sodium | Baseline and week 52 | Change from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Forced Vital Capacity (FVC) | Before randomization, 0, 4, 8, 17, 26, 34, 43 and 52 weeks after randomization | 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 |
| Morning Peak Expiratory Flow(PEF) | Daily during run-in period (14 - 18 days before Randomisation visit)and daily during 52-week randomization treatment | The change from Run-in period average to Treatment period average for each treatment group |
| Evening Peak Expiratory Flow (PEF) | Daily during run-in period (14 - 18 days before Randomisation visit) and daily during 52-week randomization treatment | The change from Run-in period average to Treatment period average for each treatment group |
| Night-time Awakening Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment | 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 |
| Daytime Breathlessness Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment | 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 |
| Daytime Cough Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | Daily during run-in period (14 - 18 days before Randomisation visit) and daily during 52-week randomization treatment | 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 |
| Total Chronic Obstructive Pulmonary Disease (COPD) Symptom Score | Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment | 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. |
| Number of COPD Exacerbations Over the Treatment Period | Daily during 52-week randomization treatment | 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. |
| Use of SABA (Salbutamol) as Reliever Medication | Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment | The change from Run-in period average to Treatment period average for each treatment group. |
| St George's Respiratory Questionnaire (SGRQ) Total Score | Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment | 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 |
| Forced Expiratory Volume in One Second (FEV1) | Before randomization, 0, 4, 8, 17, 26, 34, 43 and 52 weeks after randomization | 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 |
Countries
Japan
Participant flow
Recruitment details
The first participant entered the study on 18 December 2009, and the last participant completed the study on 20 July 2011. A total of 320 participants were enrolled at 30 centers in Japan, and 251 participants who fulfilled the randomization criteria were randomized.
Pre-assignment details
The study started with an enrolment visit, Visit 1, 1 week prior to Visit 2, and 1 week run-in period before randomization. At Visit 2 participants had to have pre-bronchodilatory forced expiratory volume in one second (FEV1) less than 80 percent of the predicted normal value.
Participants by arm
| Arm | Count |
|---|---|
| Formoterol Formoterol 9 μg twice daily | 125 |
| Standard Treatment Standard COPD (JRS guideline and GOLD) treatment | 126 |
| Total | 251 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 10 | 5 |
| Overall Study | Development of Study-Specific Withdrawal | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | PI's decision | 0 | 1 |
| Overall Study | Sever Non-Compliance to Protocol | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | Formoterol | Standard Treatment | Total |
|---|---|---|---|
| Age Continuous | 70.8 Years | 70.3 Years | 70.6 Years |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 15 Participants |
| Sex: Female, Male Male | 119 Participants | 117 Participants | 236 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 54 / 125 | 60 / 126 |
| serious Total, serious adverse events | 20 / 125 | 18 / 126 |
Outcome results
Primary
Clinical Laboratory Test: Clinical Chemistry- S-Alanine Aminotransferase
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Clinical Chemistry- S-Alanine Aminotransferase | -0.3 U/l | Standard Deviation 10 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Clinical Chemistry- S-Alanine Aminotransferase | 4.9 U/l | Standard Deviation 65.9 |
Primary
Clinical Laboratory Test: Clinical Chemistry-S-Albumin
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Clinical Chemistry-S-Albumin | 0.00 g/dl | Standard Deviation 0.28 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Clinical Chemistry-S-Albumin | 0.00 g/dl | Standard Deviation 0.23 |
Primary
Clinical Laboratory Test: Clinical Chemistry-S-Alkaline Phosphatase (ALP)
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Clinical Chemistry-S-Alkaline Phosphatase (ALP) | 3.8 U/l | Standard Deviation 44.7 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Clinical Chemistry-S-Alkaline Phosphatase (ALP) | -4.4 U/l | Standard Deviation 52.9 |
Primary
Clinical Laboratory Test: Clinical Chemistry-S-Aspartate Aminotransferase
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Clinical Chemistry-S-Aspartate Aminotransferase | 0.4 U/l | Standard Deviation 12 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Clinical Chemistry-S-Aspartate Aminotransferase | 2.6 U/l | Standard Deviation 39.3 |
Primary
Clinical Laboratory Test: Clinical Chemistry - S-Blood Urea Nitrogen (BUN)
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Clinical Chemistry - S-Blood Urea Nitrogen (BUN) | -0.48 mg/dl | Standard Deviation 4 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Clinical Chemistry - S-Blood Urea Nitrogen (BUN) | 0.07 mg/dl | Standard Deviation 3.99 |
Primary
Clinical Laboratory Test: Clinical Chemistry-S- Calcium
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Clinical Chemistry-S- Calcium | -0.02 mg/dl | Standard Deviation 0.42 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Clinical Chemistry-S- Calcium | -0.03 mg/dl | Standard Deviation 0.35 |
Primary
Clinical Laboratory Test: Clinical Chemistry-S-Creatinine
Change from Baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Clinical Chemistry-S-Creatinine | 0.009 mg/dL | Standard Deviation 0.089 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Clinical Chemistry-S-Creatinine | 0.021 mg/dL | Standard Deviation 0.117 |
Primary
Clinical Laboratory Test: Clinical Chemistry-S-Potassium
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Clinical Chemistry-S-Potassium | -0.15 mEq/L | Standard Deviation 0.34 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Clinical Chemistry-S-Potassium | -0.07 mEq/L | Standard Deviation 0.37 |
Primary
Clinical Laboratory Test: Clinical Chemistry-S-Sodium
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Clinical Chemistry-S-Sodium | -0.3 mEq/l | Standard Deviation 1.9 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Clinical Chemistry-S-Sodium | -0.2 mEq/l | Standard Deviation 2 |
Primary
Clinical Laboratory Test: Clinical Chemistry-S-Total Bilirubin
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Clinical Chemistry-S-Total Bilirubin | 0.05 mg/dL | Standard Deviation 0.22 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Clinical Chemistry-S-Total Bilirubin | 0.02 mg/dL | Standard Deviation 0.19 |
Primary
Clinical Laboratory Test: Clinical Chemistry-S-Total Protein
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Clinical Chemistry-S-Total Protein | -0.05 g/dl | Standard Deviation 0.4 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Clinical Chemistry-S-Total Protein | -0.09 g/dl | Standard Deviation 0.37 |
Primary
Clinical Laboratory Test: Haematology Basophil
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Haematology Basophil | 0.05 percentage of Basophil | Standard Deviation 0.37 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Haematology Basophil | 0.01 percentage of Basophil | Standard Deviation 0.35 |
Primary
Clinical Laboratory Test: Haematology Eosinophils
Change from baseline
Time frame: baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Haematology Eosinophils | 0.49 percentage of Eosinophil | Standard Deviation 2.21 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Haematology Eosinophils | 0.45 percentage of Eosinophil | Standard Deviation 2.45 |
Primary
Clinical Laboratory Test: Haematology -Erythrocytes
Mean change from Baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Haematology -Erythrocytes | -6.25 erythrocytes counts x10000/μl | Standard Deviation 23.8 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Haematology -Erythrocytes | -5.2 erythrocytes counts x10000/μl | Standard Deviation 27.5 |
Primary
Clinical Laboratory Test: Haematology -Haemoglobin
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Haematology -Haemoglobin | -0.29 g/dL | Standard Deviation 0.73 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Haematology -Haemoglobin | -0.20 g/dL | Standard Deviation 1.14 |
Primary
Clinical Laboratory Test: Haematology-Leucocytes
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Haematology-Leucocytes | -132.1 leukocyte count/µL | Standard Deviation 1535.3 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Haematology-Leucocytes | -289.5 leukocyte count/µL | Standard Deviation 1284.6 |
Primary
Clinical Laboratory Test: Haematology-Lymphocytes
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Haematology-Lymphocytes | -1.31 percentage of Lymphocyte | Standard Deviation 7.86 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Haematology-Lymphocytes | -0.43 percentage of Lymphocyte | Standard Deviation 7.06 |
Primary
Clinical Laboratory Test: Haematology-Monocytes
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Haematology-Monocytes | -0.01 percentage of Monocyte | Standard Deviation 1.55 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Haematology-Monocytes | -0.03 percentage of Monocyte | Standard Deviation 1.49 |
Primary
Clinical Laboratory Test: Haematology -Neutrophils
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Haematology -Neutrophils | 1.92 percentage of Neutrophil | Standard Deviation 8.32 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Haematology -Neutrophils | -0.28 percentage of Neutrophil | Standard Deviation 7.64 |
Primary
Clinical Laboratory Test: Haematology-Platelet Count
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Clinical Laboratory Test: Haematology-Platelet Count | 0.17 Platelet Count x10000/μl | Standard Deviation 3.29 |
| Arm 2 - Standard Treatment | Clinical Laboratory Test: Haematology-Platelet Count | -0.40 Platelet Count x10000/μl | Standard Deviation 4.06 |
Primary
ECG Variables - Heart Rate
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | ECG Variables - Heart Rate | 2.0 beats/min | Standard Deviation 11.4 |
| Arm 2 - Standard Treatment | ECG Variables - Heart Rate | 0.6 beats/min | Standard Deviation 12 |
Primary
ECG Variables - QTcB Interval
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | ECG Variables - QTcB Interval | 2.1 milisecond | Standard Deviation 20.6 |
| Arm 2 - Standard Treatment | ECG Variables - QTcB Interval | 1.2 milisecond | Standard Deviation 22.2 |
Primary
ECG Variables QTcF Interval
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | ECG Variables QTcF Interval | 0.5 milisecond | Standard Deviation 15.1 |
| Arm 2 - Standard Treatment | ECG Variables QTcF Interval | 1.7 milisecond | Standard Deviation 19.1 |
Primary
ECG Variables - QT Interval
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | ECG Variables - QT Interval | -2.0 milisecond | Standard Deviation 22.8 |
| Arm 2 - Standard Treatment | ECG Variables - QT Interval | 2.6 milisecond | Standard Deviation 26.7 |
Primary
ECG Variables RR Interval
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | ECG Variables RR Interval | -12.1 milisecond | Standard Deviation 7.2 |
| Arm 2 - Standard Treatment | ECG Variables RR Interval | 131.7 milisecond | Standard Deviation 124.1 |
Primary
Vital Signs - Pulse Rate
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Vital Signs - Pulse Rate | 1.5 beats/minute | Standard Deviation 10.7 |
| Arm 2 - Standard Treatment | Vital Signs - Pulse Rate | -0.1 beats/minute | Standard Deviation 10.2 |
Primary
Vital Signs- Sitting DBP
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Vital Signs- Sitting DBP | -2.7 mmHg | Standard Deviation 8.9 |
| Arm 2 - Standard Treatment | Vital Signs- Sitting DBP | -3.5 mmHg | Standard Deviation 10.1 |
Primary
Vital Signs- Sitting SBP
Change from baseline
Time frame: Baseline and week 52
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any safety data after randomisation were available were included in the safety population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Vital Signs- Sitting SBP | -2.1 mmHg | Standard Deviation 14.8 |
| Arm 2 - Standard Treatment | Vital Signs- Sitting SBP | -2.1 mmHg | Standard Deviation 16.4 |
Secondary
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
Time frame: Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any efficacy data after randomisation were available were included in the efficacy population (Full Analysis Set: FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Daytime Breathlessness Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | -0.2 units on a scale | Standard Deviation 0.7 |
| Arm 2 - Standard Treatment | Daytime Breathlessness Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | -0.2 units on a scale | Standard Deviation 0.8 |
Secondary
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
Time frame: Daily during run-in period (14 - 18 days before Randomisation visit) and daily during 52-week randomization treatment
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any efficacy data after randomisation were available were included in the efficacy population (Full Analysis Set: FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Daytime Cough Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | -0.2 units on a scale | Standard Deviation 0.8 |
| Arm 2 - Standard Treatment | Daytime Cough Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | -0.1 units on a scale | Standard Deviation 0.7 |
Secondary
Evening Peak Expiratory Flow (PEF)
The change from Run-in period average to Treatment period average for each treatment group
Time frame: Daily during run-in period (14 - 18 days before Randomisation visit) and daily during 52-week randomization treatment
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any efficacy data after randomisation were available were included in the efficacy population (Full Analysis Set: FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Evening Peak Expiratory Flow (PEF) | 9.6 Liter/minute (L/min) | Standard Deviation 34 |
| Arm 2 - Standard Treatment | Evening Peak Expiratory Flow (PEF) | 7.9 Liter/minute (L/min) | Standard Deviation 28.2 |
Secondary
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
Time frame: Before randomization, 0, 4, 8, 17, 26, 34, 43 and 52 weeks after randomization
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any efficacy data after randomisation were available were included in the efficacy population (Full Analysis Set: FAS).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm 1 - Formoterol | Forced Expiratory Volume in One Second (FEV1) | 101.46 percentage of baseline |
| Arm 2 - Standard Treatment | Forced Expiratory Volume in One Second (FEV1) | 99.42 percentage of baseline |
Secondary
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
Time frame: Before randomization, 0, 4, 8, 17, 26, 34, 43 and 52 weeks after randomization
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any efficacy data after randomisation were available were included in the efficacy population (Full Analysis Set: FAS).
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm 1 - Formoterol | Forced Vital Capacity (FVC) | 101.62 Percentage of baseline |
| Arm 2 - Standard Treatment | Forced Vital Capacity (FVC) | 99.13 Percentage of baseline |
Secondary
Morning Peak Expiratory Flow(PEF)
The change from Run-in period average to Treatment period average for each treatment group
Time frame: Daily during run-in period (14 - 18 days before Randomisation visit)and daily during 52-week randomization treatment
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any efficacy data after randomisation were available were included in the efficacy population (Full Analysis Set: FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Morning Peak Expiratory Flow(PEF) | 12.2 Liter/minute (L/min) | Standard Deviation 34.9 |
| Arm 2 - Standard Treatment | Morning Peak Expiratory Flow(PEF) | 7.3 Liter/minute (L/min) | Standard Deviation 26.2 |
Secondary
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
Time frame: Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any efficacy data after randomisation were available were included in the efficacy population (Full Analysis Set: FAS).
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Night-time Awakening Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | 0.0 units on a scale | Standard Deviation 0.4 |
| Arm 2 - Standard Treatment | Night-time Awakening Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms | -0.1 units on a scale | Standard Deviation 0.6 |
Secondary
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.
Time frame: Daily during 52-week randomization treatment
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any efficacy data after randomisation were available were included in the efficacy population (Full Analysis Set: FAS).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 - Formoterol | Number of COPD Exacerbations Over the Treatment Period | 27 number of exacerbations |
| Arm 2 - Standard Treatment | Number of COPD Exacerbations Over the Treatment Period | 19 number of exacerbations |
Secondary
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
Time frame: Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any efficacy data after randomisation were available were included in the efficacy population (Full Analysis Set: FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | St George's Respiratory Questionnaire (SGRQ) Total Score | -1.34 units on a scale | Standard Deviation 8.48 |
| Arm 2 - Standard Treatment | St George's Respiratory Questionnaire (SGRQ) Total Score | -0.57 units on a scale | Standard Deviation 7.78 |
Secondary
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.
Time frame: Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any efficacy data after randomisation were available were included in the efficacy population (Full Analysis Set: FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Total Chronic Obstructive Pulmonary Disease (COPD) Symptom Score | -0.5 units on a scale | Standard Deviation 1.2 |
| Arm 2 - Standard Treatment | Total Chronic Obstructive Pulmonary Disease (COPD) Symptom Score | -0.4 units on a scale | Standard Deviation 1.4 |
Secondary
Use of SABA (Salbutamol) as Reliever Medication
The change from Run-in period average to Treatment period average for each treatment group.
Time frame: Daily during run-in period (14 - 18 days before Randomisation visit ) and daily during 52-week randomization treatment
Population: All randomised subjects who received at least one dose of formoterol or standard COPD treatment for each treatment group respectively and for whom any efficacy data after randomisation were available were included in the efficacy population (Full Analysis Set: FAS).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 - Formoterol | Use of SABA (Salbutamol) as Reliever Medication | -0.2 Times/Day | Standard Deviation 0.7 |
| Arm 2 - Standard Treatment | Use of SABA (Salbutamol) as Reliever Medication | 0.0 Times/Day | Standard Deviation 1.1 |