Trial Outcomes & Findings for 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 (NCT NCT01047553)

NCT ID: NCT01047553

Last Updated: 2013-01-04

Results Overview

Mean change from Baseline

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 251 participants
• Primary outcome timeframe: Baseline and week 52
• Results posted on: 2013-01-04

Participant Flow

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.

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.

Participant milestones

Measure	Formoterol Formoterol 9 μg twice daily	Standard Treatment Standard COPD (JRS guideline and GOLD) treatment
Overall Study STARTED	125	126
Overall Study COMPLETED	108	117
Overall Study NOT COMPLETED	17	9

Reasons for withdrawal

Measure	Formoterol Formoterol 9 μg twice daily	Standard Treatment Standard COPD (JRS guideline and GOLD) treatment
Overall Study Adverse Event	10	5
Overall Study Withdrawal by Subject	4	2
Overall Study Development of Study-Specific Withdrawal	1	1
Overall Study Lost to Follow-up	1	0
Overall Study Sever Non-Compliance to Protocol	1	0
Overall Study PI's decision	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Formoterol n=125 Participants Formoterol 9 μg twice daily	Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment	Total n=251 Participants Total of all reporting groups
Age Continuous	70.8 Years n=5 Participants	70.3 Years n=7 Participants	70.6 Years n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Sex: Female, Male Male	119 Participants n=5 Participants	117 Participants n=7 Participants	236 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Mean change from Baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Haematology -Erythrocytes	-6.25 erythrocytes counts x10000/μl Standard Deviation 23.8	-5.2 erythrocytes counts x10000/μl Standard Deviation 27.5

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Haematology -Haemoglobin	-0.29 g/dL Standard Deviation 0.73	-0.20 g/dL Standard Deviation 1.14

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Haematology-Leucocytes	-132.1 leukocyte count/µL Standard Deviation 1535.3	-289.5 leukocyte count/µL Standard Deviation 1284.6

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Haematology-Platelet Count	0.17 Platelet Count x10000/μl Standard Deviation 3.29	-0.40 Platelet Count x10000/μl Standard Deviation 4.06

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Haematology Eosinophils	0.49 percentage of Eosinophil Standard Deviation 2.21	0.45 percentage of Eosinophil Standard Deviation 2.45

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Haematology Basophil	0.05 percentage of Basophil Standard Deviation 0.37	0.01 percentage of Basophil Standard Deviation 0.35

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Haematology-Lymphocytes	-1.31 percentage of Lymphocyte Standard Deviation 7.86	-0.43 percentage of Lymphocyte Standard Deviation 7.06

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Haematology-Monocytes	-0.01 percentage of Monocyte Standard Deviation 1.55	-0.03 percentage of Monocyte Standard Deviation 1.49

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Haematology -Neutrophils	1.92 percentage of Neutrophil Standard Deviation 8.32	-0.28 percentage of Neutrophil Standard Deviation 7.64

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Clinical Chemistry- S-Alanine Aminotransferase	-0.3 U/l Standard Deviation 10.0	4.9 U/l Standard Deviation 65.9

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Clinical Chemistry-S-Aspartate Aminotransferase	0.4 U/l Standard Deviation 12.0	2.6 U/l Standard Deviation 39.3

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Clinical Chemistry-S-Alkaline Phosphatase (ALP)	3.8 U/l Standard Deviation 44.7	-4.4 U/l Standard Deviation 52.9

PRIMARY outcome

Timeframe: 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.

Change from Baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Clinical Chemistry-S-Creatinine	0.009 mg/dL Standard Deviation 0.089	0.021 mg/dL Standard Deviation 0.117

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Clinical Chemistry-S-Total Bilirubin	0.05 mg/dL Standard Deviation 0.22	0.02 mg/dL Standard Deviation 0.19

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Clinical Chemistry-S-Sodium	-0.3 mEq/l Standard Deviation 1.9	-0.2 mEq/l Standard Deviation 2.0

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Clinical Chemistry-S-Potassium	-0.15 mEq/L Standard Deviation 0.34	-0.07 mEq/L Standard Deviation 0.37

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Clinical Chemistry-S- Calcium	-0.02 mg/dl Standard Deviation 0.42	-0.03 mg/dl Standard Deviation 0.35

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Clinical Chemistry-S-Albumin	0.00 g/dl Standard Deviation 0.28	0.00 g/dl Standard Deviation 0.23

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Clinical Chemistry-S-Total Protein	-0.05 g/dl Standard Deviation 0.40	-0.09 g/dl Standard Deviation 0.37

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Clinical Laboratory Test: Clinical Chemistry - S-Blood Urea Nitrogen (BUN)	-0.48 mg/dl Standard Deviation 4.00	0.07 mg/dl Standard Deviation 3.99

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Vital Signs- Sitting SBP	-2.1 mmHg Standard Deviation 14.8	-2.1 mmHg Standard Deviation 16.4

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Vital Signs- Sitting DBP	-2.7 mmHg Standard Deviation 8.9	-3.5 mmHg Standard Deviation 10.1

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Vital Signs - Pulse Rate	1.5 beats/minute Standard Deviation 10.7	-0.1 beats/minute Standard Deviation 10.2

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=121 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=119 Participants Standard COPD (JRS guideline and GOLD) treatment
ECG Variables - Heart Rate	2.0 beats/min Standard Deviation 11.4	0.6 beats/min Standard Deviation 12.0

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=121 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=119 Participants Standard COPD (JRS guideline and GOLD) treatment
ECG Variables - QT Interval	-2.0 milisecond Standard Deviation 22.8	2.6 milisecond Standard Deviation 26.7

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=121 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=119 Participants Standard COPD (JRS guideline and GOLD) treatment
ECG Variables - QTcB Interval	2.1 milisecond Standard Deviation 20.6	1.2 milisecond Standard Deviation 22.2

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=121 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=119 Participants Standard COPD (JRS guideline and GOLD) treatment
ECG Variables QTcF Interval	0.5 milisecond Standard Deviation 15.1	1.7 milisecond Standard Deviation 19.1

PRIMARY outcome

Timeframe: 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.

Change from baseline

Outcome measures

Measure	Arm 1 - Formoterol n=121 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=119 Participants Standard COPD (JRS guideline and GOLD) treatment
ECG Variables RR Interval	-12.1 milisecond Standard Deviation 7.2	131.7 milisecond Standard Deviation 124.1

SECONDARY outcome

Timeframe: 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).

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

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Forced Expiratory Volume in One Second (FEV1)	101.46 percentage of baseline Interval 68.9 to 139.2	99.42 percentage of baseline Interval 80.3 to 165.1

SECONDARY outcome

Timeframe: 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).

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

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Forced Vital Capacity (FVC)	101.62 Percentage of baseline Interval 76.9 to 157.3	99.13 Percentage of baseline Interval 75.3 to 163.0

SECONDARY outcome

Timeframe: 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).

The change from Run-in period average to Treatment period average for each treatment group

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Morning Peak Expiratory Flow(PEF)	12.2 Liter/minute (L/min) Standard Deviation 34.9	7.3 Liter/minute (L/min) Standard Deviation 26.2

SECONDARY outcome

Timeframe: 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).

The change from Run-in period average to Treatment period average for each treatment group

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Evening Peak Expiratory Flow (PEF)	9.6 Liter/minute (L/min) Standard Deviation 34.0	7.9 Liter/minute (L/min) Standard Deviation 28.2

SECONDARY outcome

Timeframe: 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).

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

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Night-time Awakening Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms	0.0 units on a scale Standard Deviation 0.4	-0.1 units on a scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: 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).

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

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Daytime Breathlessness Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms	-0.2 units on a scale Standard Deviation 0.7	-0.2 units on a scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: 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).

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

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Daytime Cough Due to Chronic Obstructive Pulmonary Disease (COPD) Symptoms	-0.2 units on a scale Standard Deviation 0.8	-0.1 units on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Total Chronic Obstructive Pulmonary Disease (COPD) Symptom Score	-0.5 units on a scale Standard Deviation 1.2	-0.4 units on a scale Standard Deviation 1.4

SECONDARY outcome

Timeframe: 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).

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.

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Number of COPD Exacerbations Over the Treatment Period	27 number of exacerbations	19 number of exacerbations

SECONDARY outcome

Timeframe: 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).

The change from Run-in period average to Treatment period average for each treatment group.

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
Use of SABA (Salbutamol) as Reliever Medication	-0.2 Times/Day Standard Deviation 0.7	0.0 Times/Day Standard Deviation 1.1

SECONDARY outcome

Timeframe: 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).

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

Outcome measures

Measure	Arm 1 - Formoterol n=125 Participants Formoterol 9 μg twice daily	Arm 2 - Standard Treatment n=126 Participants Standard COPD (JRS guideline and GOLD) treatment
St George's Respiratory Questionnaire (SGRQ) Total Score	-1.34 units on a scale Standard Deviation 8.48	-0.57 units on a scale Standard Deviation 7.78

Adverse Events

Formoterol

Serious events: 20 serious events

Other events: 54 other events

Deaths: 0 deaths

Standard Treatment

Serious events: 18 serious events

Other events: 60 other events

Deaths: 0 deaths

Serious adverse events

Measure	Formoterol n=125 participants at risk Formoterol 9 μg twice daily	Standard Treatment n=126 participants at risk Standard COPD (JRS guideline and GOLD) treatment
Vascular disorders Aortic Dissection	0.80% 1/125	0.00% 0/126
Reproductive system and breast disorders Spermatic Cord Disorder	0.80% 1/125	0.00% 0/126
Psychiatric disorders Depression	0.80% 1/125	0.00% 0/126
Investigations Chest X-Ray Abnormal	0.80% 1/125	0.00% 0/126
General disorders Device Failure	0.80% 1/125	0.00% 0/126
Cardiac disorders Palpitations	0.80% 1/125	0.00% 0/126
Cardiac disorders Myocardial Ischaemia	0.80% 1/125	0.00% 0/126
Cardiac disorders Cardiac Failure Congestive	0.80% 1/125	0.00% 0/126
Cardiac disorders Angina Pectoris	0.80% 1/125	0.00% 0/126
Gastrointestinal disorders Stomach Mass	0.00% 0/125	0.79% 1/126
Gastrointestinal disorders Inguinal Hernia	0.80% 1/125	0.79% 1/126
Eye disorders Visual Acuity Reduced	0.00% 0/125	0.79% 1/126
Eye disorders Cataract	0.80% 1/125	0.79% 1/126
Nervous system disorders Lacunar Infarction	0.00% 0/125	0.79% 1/126
Nervous system disorders Loss Of Consciousness	0.00% 0/125	0.79% 1/126
Nervous system disorders Epilepsy	0.00% 0/125	0.79% 1/126
Nervous system disorders Cerebral Infarction	0.00% 0/125	0.79% 1/126
Nervous system disorders Brain Stem Infarction	0.00% 0/125	0.79% 1/126
Injury, poisoning and procedural complications Venom Poisoning	0.80% 1/125	0.00% 0/126
Injury, poisoning and procedural complications Thoracic Vertebral Fracture	0.00% 0/125	0.79% 1/126
Injury, poisoning and procedural complications Tibia Fracture	0.80% 1/125	0.00% 0/126
Injury, poisoning and procedural complications Spinal Cord Injury Cervical	0.00% 0/125	0.79% 1/126
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Neoplasm Malignant	0.80% 1/125	0.00% 0/126
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal Squamous Cell Carcinoma Stage 0	0.00% 0/125	0.79% 1/126
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone Neoplasm	0.00% 0/125	0.79% 1/126
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Cancer	0.00% 0/125	1.6% 2/126
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric Cancer	0.80% 1/125	0.79% 1/126
Infections and infestations Pharyngitis	0.80% 1/125	0.00% 0/126
Infections and infestations Pneumonia	3.2% 4/125	0.79% 1/126
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.80% 1/125	0.00% 0/126
Respiratory, thoracic and mediastinal disorders Dyspnoea Exertional	0.00% 0/125	0.79% 1/126
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.80% 1/125	0.00% 0/126
Respiratory, thoracic and mediastinal disorders CHRONIC OBSTRUCTIVE PULMONARY DISEASE	4.0% 5/125	3.2% 4/126
Psychiatric disorders Bipolar Disorder	0.00% 0/125	0.79% 1/126
Reproductive system and breast disorders SPERMATIC CORD DISORDER	0.80% 1/125	0.00% 0/126

Other adverse events

Measure	Formoterol n=125 participants at risk Formoterol 9 μg twice daily	Standard Treatment n=126 participants at risk Standard COPD (JRS guideline and GOLD) treatment
Skin and subcutaneous tissue disorders Urticaria	2.4% 3/125	0.00% 0/126
Gastrointestinal disorders Stomatitis	2.4% 3/125	0.00% 0/126
Musculoskeletal and connective tissue disorders Periarthritis	2.4% 3/125	0.00% 0/126
Skin and subcutaneous tissue disorders Dermatitis Contact	2.4% 3/125	0.00% 0/126
Infections and infestations Influenza	0.80% 1/125	2.4% 3/126
Hepatobiliary disorders Hepatic Function Abnormal	0.80% 1/125	2.4% 3/126
Cardiac disorders Palpitations	2.4% 3/125	1.6% 2/126
Gastrointestinal disorders Nausea	2.4% 3/125	1.6% 2/126
Skin and subcutaneous tissue disorders Eczema	3.2% 4/125	0.79% 1/126
Infections and infestations Upper Respiratory Tract Infection	3.2% 4/125	1.6% 2/126
Nervous system disorders Headache	1.6% 2/125	3.2% 4/126
Injury, poisoning and procedural complications Contusion	3.2% 4/125	2.4% 3/126
Infections and infestations Rhinitis	4.0% 5/125	1.6% 2/126
Psychiatric disorders Insomnia	2.4% 3/125	3.2% 4/126
Vascular disorders Hypertension	2.4% 3/125	4.0% 5/126
Gastrointestinal disorders Gastritis	2.4% 3/125	4.0% 5/126
Nervous system disorders Dizziness	4.8% 6/125	1.6% 2/126
Gastrointestinal disorders Constipation	4.0% 5/125	3.2% 4/126
Eye disorders Conjunctivitis	4.0% 5/125	4.0% 5/126
Infections and infestations Pneumonia	6.4% 8/125	2.4% 3/126
Infections and infestations Pharyngitis	5.6% 7/125	3.2% 4/126
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	7.2% 9/125	4.0% 5/126
Infections and infestations Bronchitis	4.0% 5/125	7.1% 9/126
Musculoskeletal and connective tissue disorders Back Pain	10.4% 13/125	1.6% 2/126
Infections and infestations NASOPHARYNGITIS	33.6% 42/125	42.1% 53/126

Additional Information

Gerard Lynch

AstraZeneca

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER