Trial Outcomes & Findings for Evaluation of Efficacy and Safety of Formoterol in Patients With COPD Compared With Placebo in Patients in Japan, EU (NCT NCT00628862)

NCT ID: NCT00628862

Last Updated: 2012-10-25

Results Overview

FEV1 (expressed as litres \[L\]) is a spirometric measure of lung function. FEV1 was measured 60 minutes after administration of study drug. The results are expressed as a percentage in relation to the baseline value.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 613 participants
• Primary outcome timeframe: from baseline up to 12 weeks
• Results posted on: 2012-10-25

Participant Flow

Outpatients, male or female aged ≥ 40 years with moderate to severe chronic obstructive pulmonary disease (COPD). 766 subjects enrolled; 153 excluded: 96 for incorrect enrollment, 17 for adverse events, 32 for voluntary discontinuation, 1 for non-compliance with protocol, 7 for other reasons. 613 were randomised.

Participant milestones

Measure	Formoterol 4.5 Bid Formoterol 4.5 ug bid	Formoterol 9.0 Bid Formoterol 9.0 ug bid	Placebo Placebo
Overall Study STARTED	206	199	208
Overall Study COMPLETED	195	182	186
Overall Study NOT COMPLETED	11	17	22

Reasons for withdrawal

Measure	Formoterol 4.5 Bid Formoterol 4.5 ug bid	Formoterol 9.0 Bid Formoterol 9.0 ug bid	Placebo Placebo
Overall Study Adverse Event	6	8	10
Overall Study Withdrawal by Subject	4	6	11
Overall Study Lost to Follow-up	0	2	1
Overall Study Protocol Violation	1	0	0
Overall Study COPD Exacerbation	0	1	0

Baseline Characteristics

Evaluation of Efficacy and Safety of Formoterol in Patients With COPD Compared With Placebo in Patients in Japan, EU

Baseline characteristics by cohort

Measure	Formoterol 4.5 Bid n=206 Participants Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=199 Participants Formoterol 9.0 ug bid	Placebo n=208 Participants Placebo	Total n=613 Participants Total of all reporting groups
Age Continuous	66.7 Years STANDARD_DEVIATION 9.4 • n=5 Participants	67.2 Years STANDARD_DEVIATION 9.2 • n=7 Participants	66.3 Years STANDARD_DEVIATION 9.7 • n=5 Participants	66.75 Years STANDARD_DEVIATION 9.4 • n=4 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	29 Participants n=7 Participants	22 Participants n=5 Participants	74 Participants n=4 Participants
Sex: Female, Male Male	183 Participants n=5 Participants	170 Participants n=7 Participants	186 Participants n=5 Participants	539 Participants n=4 Participants

PRIMARY outcome

Timeframe: from baseline up to 12 weeks

FEV1 (expressed as litres [L]) is a spirometric measure of lung function. FEV1 was measured 60 minutes after administration of study drug. The results are expressed as a percentage in relation to the baseline value.

Outcome measures

Measure	Formoterol 4.5 Bid n=206 Participants Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=199 Participants Formoterol 9.0 ug bid	Placebo n=208 Participants Placebo
Forced Expiratory Volume in 1 Second (FEV1; L) 60 Minutes Post-dose	112.9 percent of baseline Interval 75.1 to 177.0	113.36 percent of baseline Interval 66.2 to 184.0	101.28 percent of baseline Interval 58.3 to 189.1

SECONDARY outcome

Timeframe: from baseline up to 12 weeks

Forced Vital Capacity (FVC) is a spirometric measure of lung function. FVC was measured 60 minutes after administration of study drug. The results are expressed as a percentage in relation to the baseline value

Outcome measures

Measure	Formoterol 4.5 Bid n=206 Participants Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=199 Participants Formoterol 9.0 ug bid	Placebo n=208 Participants Placebo
Forced Vital Capacity (FVC) 60 Minutes Post-dose	109.73 percent of baseline Interval 81.2 to 162.0	109.92 percent of baseline Interval 83.2 to 200.9	102.11 percent of baseline Interval 71.2 to 212.7

SECONDARY outcome

Timeframe: baseline at week 0 and pre-dose at weeks 4, 8 and 12

Lung function (FEV1) was measured before administrations of the study drug (pre-dose). The results are expressed as a percentage of mean FEV1 over visists 4-6 in relation to the baseline (visit 3) value

Outcome measures

Measure	Formoterol 4.5 Bid n=206 Participants Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=196 Participants Formoterol 9.0 ug bid	Placebo n=204 Participants Placebo
FEV1 Pre-dose	104.54 percent of baseline Interval 73.3 to 175.0	104.65 percent of baseline Interval 71.0 to 172.6	99.77 percent of baseline Interval 56.5 to 183.6

SECONDARY outcome

Timeframe: baseline at week 0 and pre-dose at weeks 4, 8 and 12

Lung function (FVC) was measured before administrations of the study drug (pre-dose). The results are expressed as a percentage of mean FEV1 over visists 4-6 in relation to the baseline (visit 3) value

Outcome measures

Measure	Formoterol 4.5 Bid n=206 Participants Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=196 Participants Formoterol 9.0 ug bid	Placebo n=204 Participants Placebo
FVC Pre-dose	103.62 percent of baseline Interval 77.7 to 149.8	103.36 percent of baseline Interval 68.9 to 162.7	100.73 percent of baseline Interval 70.8 to 211.9

SECONDARY outcome

Timeframe: baseline and 5 minutes anter first dose

Lung function (FEV1) was measured 5 minutes after the first dose of study drug. The results are expressed as a percentage in relation to the baseline value

Outcome measures

Measure	Formoterol 4.5 Bid n=206 Participants Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=197 Participants Formoterol 9.0 ug bid	Placebo n=207 Participants Placebo
FEV1 5 Minutes Post-dose	110.16 percent of baseline Interval 65.6 to 156.5	110.24 percent of baseline Interval 80.6 to 155.1	101.25 percent of baseline Interval 79.4 to 121.6

SECONDARY outcome

Timeframe: baseline and 5 minutes anter first dose

Lung function (FVC) was measured 5 minutes after the first dose of study drug, The results are expressed as a percentage in relation to the baseline value

Outcome measures

Measure	Formoterol 4.5 Bid n=206 Participants Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=197 Participants Formoterol 9.0 ug bid	Placebo n=207 Participants Placebo
FVC 5 Minutes Post-dose	108.50 percent of baseline Interval 89.9 to 143.2	108.88 percent of baseline Interval 81.5 to 153.4	101.59 percent of baseline Interval 84.3 to 124.7

SECONDARY outcome

Timeframe: run-in period and 12 week

Patients were asked to measure and record lung function (peak expiratory flow [PEF] measured in the morning). Average values over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value

Outcome measures

Measure	Formoterol 4.5 Bid n=206 Participants Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=198 Participants Formoterol 9.0 ug bid	Placebo n=205 Participants Placebo
Change in Peak Expiratory Flow (PEF), Morning	16.27 L/min Standard Deviation 27.90	18.34 L/min Standard Deviation 26.19	3.60 L/min Standard Deviation 27.08

SECONDARY outcome

Timeframe: run-in period and 12 week

Patients were asked to measure and record lung function (peak expiratory flow [PEF] measured in the evening). Average values over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value

Outcome measures

Measure	Formoterol 4.5 Bid n=206 Participants Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=198 Participants Formoterol 9.0 ug bid	Placebo n=205 Participants Placebo
Change in Peak Expiratory Flow (PEF), Evening	13.15 L/min Standard Deviation 27.52	15.76 L/min Standard Deviation 25.22	2.36 L/min Standard Deviation 26.43

SECONDARY outcome

Timeframe: run-in period up to 12 weeks

Patients were asked to record the night-time awakenings due to symptoms (scored from 0-4 with 4 being the most severe). Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value

Outcome measures

Measure	Formoterol 4.5 Bid n=206 Participants Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=198 Participants Formoterol 9.0 ug bid	Placebo n=207 Participants Placebo
Change in Night-time Awakenings Due to Symptoms	-0.1318 scores on a scale per day Standard Deviation 0.4791	-0.1748 scores on a scale per day Standard Deviation 0.5517	-0.0466 scores on a scale per day Standard Deviation 0.4900

SECONDARY outcome

Timeframe: run-in period up to 12 weeks

Patients were asked to record breathlessness (scored from 0-4 with 4 being the most severe). Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value

Outcome measures

Measure	Formoterol 4.5 Bid n=206 Participants Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=198 Participants Formoterol 9.0 ug bid	Placebo n=207 Participants Placebo
Breathlessness	-0.4068 scores on a scale per day Standard Deviation 0.6193	-0.4531 scores on a scale per day Standard Deviation 0.5511	-0.2626 scores on a scale per day Standard Deviation 0.5899

SECONDARY outcome

Timeframe: run-in period up to 12 weeks

Patients were asked to record cough (scored from 0-4 with 4 being the most severe). Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value

Outcome measures

Measure	Formoterol 4.5 Bid n=206 Participants Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=198 Participants Formoterol 9.0 ug bid	Placebo n=207 Participants Placebo
Cough	-0.3250 scores on a scale per day Standard Deviation 0.6424	-0.4088 scores on a scale per day Standard Deviation 0.6374	-0.2016 scores on a scale per day Standard Deviation 0.6233

SECONDARY outcome

Timeframe: 12 weeks (end of run-in to last visit)

Patients were asked to record reliever medication use. Period averages over the last 10 days of the run-in period and the whole treatment period were calculated. The results are expressed as the change from the run-in period average value

Outcome measures

Measure	Formoterol 4.5 Bid n=204 Participants Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=196 Participants Formoterol 9.0 ug bid	Placebo n=207 Participants Placebo
Use of Reliever Medication	-0.60 medication doses per day Standard Deviation 1.47	-0.97 medication doses per day Standard Deviation 1.88	-0.23 medication doses per day Standard Deviation 1.25

SECONDARY outcome

Timeframe: 12 weeks (end of run-in to last visit)

Patients were asked to complete the St George's Respiratory Questionnaire (SGRQ). Subscale symptom score ranges from 0 to 100% and measures the effect of respiratory symptoms, frequency, and severity on quality of life. A score of 0 indicates the best possible status. Results are expressed as the change from baseline score with a decrease in score indicating improvement.

Outcome measures

Measure	Formoterol 4.5 Bid n=203 Participants Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=191 Participants Formoterol 9.0 ug bid	Placebo n=206 Participants Placebo
St George's Respiratory Questionnaire (SGRQ)	-5.46 Scores on a scale Standard Deviation 12.12	-6.38 Scores on a scale Standard Deviation 10.77	-2.02 Scores on a scale Standard Deviation 12.98

Adverse Events

Formoterol 4.5 Bid

Serious events: 6 serious events

Other events: 33 other events

Deaths: 0 deaths

Formoterol 9.0 Bid

Serious events: 7 serious events

Other events: 31 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Measure	Formoterol 4.5 Bid n=206 participants at risk Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=199 participants at risk Formoterol 9.0 ug bid	Placebo n=208 participants at risk Placebo
General disorders Death	0.49% 1/206	0.00% 0/199	0.00% 0/208
Infections and infestations Pneumonia	0.97% 2/206	1.0% 2/199	0.00% 0/208
Infections and infestations Lobar Pneumonia	0.00% 0/206	0.50% 1/199	0.00% 0/208
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder Cancer	0.00% 0/206	0.00% 0/199	0.48% 1/208
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric Cancer	0.00% 0/206	0.50% 1/199	0.00% 0/208
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate Caner	0.49% 1/206	0.00% 0/199	0.00% 0/208
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	0.00% 0/206	0.50% 1/199	0.96% 2/208
Metabolism and nutrition disorders Diabetes Mellitus	0.49% 1/206	0.00% 0/199	0.00% 0/208
Metabolism and nutrition disorders Hypoglycaemic Unconsciousness	0.00% 0/206	0.50% 1/199	0.00% 0/208
Cardiac disorders Angina Pectoris	0.00% 0/206	0.50% 1/199	0.00% 0/208
Gastrointestinal disorders Ileus	0.00% 0/206	0.00% 0/199	0.48% 1/208
Cardiac disorders Cardiopulmonary Failure	0.49% 1/206	0.00% 0/199	0.00% 0/208

Other adverse events

Measure	Formoterol 4.5 Bid n=206 participants at risk Formoterol 4.5 ug bid	Formoterol 9.0 Bid n=199 participants at risk Formoterol 9.0 ug bid	Placebo n=208 participants at risk Placebo
Respiratory, thoracic and mediastinal disorders Chronic Obstructive Pulmonary Disease	4.9% 10/206	3.5% 7/199	7.2% 15/208
Infections and infestations Nasopharyngitis	11.7% 24/206	12.6% 25/199	9.6% 20/208

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: LTE60