Trial Outcomes & Findings for A 6-week Dose Ranging Study of CHF 5259 pMDI in Subjects With Chronic Obstructive Pulmonary Disease (NCT NCT03084796)
NCT ID: NCT03084796
Last Updated: 2021-06-15
Results Overview
Change from baseline in FEV1 AUC(0-12h), normalized by time, at the end of treatment (Week 6). Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 at Week 6 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (12 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-12h)=Mean FEV1 after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time;
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
733 participants
Primary outcome timeframe
Baseline, Week 6
Results posted on
2021-06-15
Participant Flow
Participant milestones
| Measure |
Treatment A
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
Placebo Control
Placebo: Placebo Control
|
Treatment F
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
121
|
123
|
122
|
123
|
121
|
123
|
|
Overall Study
COMPLETED
|
114
|
113
|
110
|
119
|
110
|
116
|
|
Overall Study
NOT COMPLETED
|
7
|
10
|
12
|
4
|
11
|
7
|
Reasons for withdrawal
| Measure |
Treatment A
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
Placebo Control
Placebo: Placebo Control
|
Treatment F
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
4
|
5
|
6
|
2
|
3
|
5
|
|
Overall Study
Withdrawal by Subject
|
3
|
5
|
2
|
1
|
3
|
0
|
|
Overall Study
Protocol Violation
|
0
|
0
|
1
|
0
|
1
|
1
|
|
Overall Study
Lack of Efficacy
|
0
|
0
|
1
|
0
|
1
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
1
|
1
|
3
|
1
|
|
Overall Study
Randomization error
|
0
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
A 6-week Dose Ranging Study of CHF 5259 pMDI in Subjects With Chronic Obstructive Pulmonary Disease
Baseline characteristics by cohort
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI, 6.25 μg, 1 inhalation bid; 12.5 μg TDD
CHF 5259 Dose Response: Test one of 4 different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI 12.5 μg, 1 inhalation bid; 25 μg TDD
CHF 5259 Dose Response: Test one of 4 different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI 12.5 μg, 2 inhalations bid; 50 μg TDD
CHF 5259 Dose Response: Test one of 4 different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI 25 μg, 2 inhalations bid; 100 μg TDD
CHF 5259 Dose Response: Test one of 4 different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo 2 inhalations of CHF 5259 pMDI-matched Placebo bid
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 μg, SPIRIVA® HandiHaler®, 2 inhalations od of the content of 1 capsule; 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
Total
n=732 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
64.1 years
STANDARD_DEVIATION 9.13 • n=5 Participants
|
65.3 years
STANDARD_DEVIATION 9.10 • n=7 Participants
|
65.3 years
STANDARD_DEVIATION 8.16 • n=5 Participants
|
64.9 years
STANDARD_DEVIATION 9.11 • n=4 Participants
|
64.9 years
STANDARD_DEVIATION 9.25 • n=21 Participants
|
63.8 years
STANDARD_DEVIATION 9.55 • n=8 Participants
|
64.7 years
STANDARD_DEVIATION 9.05 • n=8 Participants
|
|
Age, Customized
< 65 years
|
59 Participants
n=5 Participants
|
53 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
62 Participants
n=4 Participants
|
60 Participants
n=21 Participants
|
62 Participants
n=8 Participants
|
352 Participants
n=8 Participants
|
|
Age, Customized
65-84 years
|
60 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
65 Participants
n=5 Participants
|
60 Participants
n=4 Participants
|
58 Participants
n=21 Participants
|
59 Participants
n=8 Participants
|
370 Participants
n=8 Participants
|
|
Age, Customized
> 85 years
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
10 Participants
n=8 Participants
|
|
Sex: Female, Male
Female
|
58 Participants
n=5 Participants
|
68 Participants
n=7 Participants
|
67 Participants
n=5 Participants
|
65 Participants
n=4 Participants
|
52 Participants
n=21 Participants
|
57 Participants
n=8 Participants
|
367 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
63 Participants
n=5 Participants
|
55 Participants
n=7 Participants
|
54 Participants
n=5 Participants
|
58 Participants
n=4 Participants
|
69 Participants
n=21 Participants
|
66 Participants
n=8 Participants
|
365 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
7 Participants
n=8 Participants
|
51 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
114 Participants
n=5 Participants
|
114 Participants
n=7 Participants
|
109 Participants
n=5 Participants
|
112 Participants
n=4 Participants
|
115 Participants
n=21 Participants
|
116 Participants
n=8 Participants
|
680 Participants
n=8 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
2 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
1 Participants
n=8 Participants
|
4 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Black or African American
|
13 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
14 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
10 Participants
n=8 Participants
|
69 Participants
n=8 Participants
|
|
Race (NIH/OMB)
White
|
107 Participants
n=5 Participants
|
110 Participants
n=7 Participants
|
107 Participants
n=5 Participants
|
108 Participants
n=4 Participants
|
104 Participants
n=21 Participants
|
110 Participants
n=8 Participants
|
646 Participants
n=8 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
11 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
121 Participants
n=5 Participants
|
123 Participants
n=7 Participants
|
121 Participants
n=5 Participants
|
123 Participants
n=4 Participants
|
121 Participants
n=21 Participants
|
123 Participants
n=8 Participants
|
732 Participants
n=8 Participants
|
|
Weight
|
81.81 kg
STANDARD_DEVIATION 20.64 • n=5 Participants
|
83.82 kg
STANDARD_DEVIATION 19.33 • n=7 Participants
|
82.12 kg
STANDARD_DEVIATION 22.70 • n=5 Participants
|
84.23 kg
STANDARD_DEVIATION 22.41 • n=4 Participants
|
84.43 kg
STANDARD_DEVIATION 21.82 • n=21 Participants
|
80.67 kg
STANDARD_DEVIATION 17.40 • n=8 Participants
|
82.85 kg
STANDARD_DEVIATION 20.77 • n=8 Participants
|
|
Height
|
168.95 cm
STANDARD_DEVIATION 8.76 • n=5 Participants
|
169.38 cm
STANDARD_DEVIATION 9.74 • n=7 Participants
|
169.21 cm
STANDARD_DEVIATION 9.67 • n=5 Participants
|
168.17 cm
STANDARD_DEVIATION 9.57 • n=4 Participants
|
169.34 cm
STANDARD_DEVIATION 9.56 • n=21 Participants
|
169.53 cm
STANDARD_DEVIATION 9.67 • n=8 Participants
|
169.10 cm
STANDARD_DEVIATION 9.48 • n=8 Participants
|
|
Body Mass Index (BMI)
|
28.67 kg/m^2
STANDARD_DEVIATION 7.05 • n=5 Participants
|
29.13 kg/m^2
STANDARD_DEVIATION 5.98 • n=7 Participants
|
28.52 kg/m^2
STANDARD_DEVIATION 6.77 • n=5 Participants
|
29.62 kg/m^2
STANDARD_DEVIATION 6.73 • n=4 Participants
|
29.26 kg/m^2
STANDARD_DEVIATION 6.49 • n=21 Participants
|
28.05 kg/m^2
STANDARD_DEVIATION 5.54 • n=8 Participants
|
28.88 kg/m^2
STANDARD_DEVIATION 6.45 • n=8 Participants
|
|
Time since first diagnosis of COPD
|
92.80 months
n=5 Participants
|
99.60 months
n=7 Participants
|
97.40 months
n=5 Participants
|
94.00 months
n=4 Participants
|
103.40 months
n=21 Participants
|
74.40 months
n=8 Participants
|
94.55 months
n=8 Participants
|
|
Age at first diagnosis of COPD
|
54.98 years
STANDARD_DEVIATION 9.31 • n=5 Participants
|
55.45 years
STANDARD_DEVIATION 9.29 • n=7 Participants
|
55.38 years
STANDARD_DEVIATION 8.46 • n=5 Participants
|
56.40 years
STANDARD_DEVIATION 9.41 • n=4 Participants
|
55.12 years
STANDARD_DEVIATION 8.85 • n=21 Participants
|
55.65 years
STANDARD_DEVIATION 10.19 • n=8 Participants
|
55.50 years
STANDARD_DEVIATION 9.25 • n=8 Participants
|
|
COPD medication category at study entry
Inhaled LAMA
|
24 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
31 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
25 Participants
n=21 Participants
|
27 Participants
n=8 Participants
|
151 Participants
n=8 Participants
|
|
COPD medication category at study entry
Inhaled ICS and LABA (free combination)
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
6 Participants
n=8 Participants
|
|
COPD medication category at study entry
Inhaled ICS/LABA (fixed combination)
|
77 Participants
n=5 Participants
|
89 Participants
n=7 Participants
|
74 Participants
n=5 Participants
|
92 Participants
n=4 Participants
|
78 Participants
n=21 Participants
|
81 Participants
n=8 Participants
|
491 Participants
n=8 Participants
|
|
COPD medication category at study entry
Inhaled ICS and LAMA
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
8 Participants
n=8 Participants
|
|
COPD medication category at study entry
Inhaled ICS+LABA+LAMA (free or fixed combination)
|
11 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
13 Participants
n=21 Participants
|
8 Participants
n=8 Participants
|
52 Participants
n=8 Participants
|
|
COPD medication category at study entry
Inhaled LABA/LAMA (fixed combination)
|
6 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
3 Participants
n=8 Participants
|
24 Participants
n=8 Participants
|
|
Smoking habits
Current smoker
|
61 Participants
n=5 Participants
|
59 Participants
n=7 Participants
|
59 Participants
n=5 Participants
|
68 Participants
n=4 Participants
|
55 Participants
n=21 Participants
|
67 Participants
n=8 Participants
|
369 Participants
n=8 Participants
|
|
Smoking habits
Ex-smoker
|
60 Participants
n=5 Participants
|
64 Participants
n=7 Participants
|
62 Participants
n=5 Participants
|
55 Participants
n=4 Participants
|
66 Participants
n=21 Participants
|
56 Participants
n=8 Participants
|
363 Participants
n=8 Participants
|
|
Duration of smoking
|
42.19 years
STANDARD_DEVIATION 9.74 • n=5 Participants
|
42.98 years
STANDARD_DEVIATION 9.86 • n=7 Participants
|
40.71 years
STANDARD_DEVIATION 10.46 • n=5 Participants
|
42.78 years
STANDARD_DEVIATION 10.44 • n=4 Participants
|
41.34 years
STANDARD_DEVIATION 10.39 • n=21 Participants
|
40.79 years
STANDARD_DEVIATION 10.83 • n=8 Participants
|
41.80 years
STANDARD_DEVIATION 10.30 • n=8 Participants
|
|
Number of pack-years
|
45.0 pack-years
n=5 Participants
|
49.0 pack-years
n=7 Participants
|
45.0 pack-years
n=5 Participants
|
45.0 pack-years
n=4 Participants
|
45.0 pack-years
n=21 Participants
|
43.0 pack-years
n=8 Participants
|
45.0 pack-years
n=8 Participants
|
|
FEV1 (L) at baseline
|
1.440 litres
STANDARD_DEVIATION 0.432 • n=5 Participants
|
1.428 litres
STANDARD_DEVIATION 0.439 • n=7 Participants
|
1.434 litres
STANDARD_DEVIATION 0.472 • n=5 Participants
|
1.420 litres
STANDARD_DEVIATION 0.419 • n=4 Participants
|
1.415 litres
STANDARD_DEVIATION 0.433 • n=21 Participants
|
1.443 litres
STANDARD_DEVIATION 0.487 • n=8 Participants
|
1.430 litres
STANDARD_DEVIATION 0.446 • n=8 Participants
|
|
FVC at baseline
|
2.717 litres
STANDARD_DEVIATION 0.754 • n=5 Participants
|
2.719 litres
STANDARD_DEVIATION 0.775 • n=7 Participants
|
2.669 litres
STANDARD_DEVIATION 0.725 • n=5 Participants
|
2.630 litres
STANDARD_DEVIATION 0.719 • n=4 Participants
|
2.683 litres
STANDARD_DEVIATION 0.736 • n=21 Participants
|
2.746 litres
STANDARD_DEVIATION 0.809 • n=8 Participants
|
2.694 litres
STANDARD_DEVIATION 0.752 • n=8 Participants
|
|
IC at baseline
|
2.020 litres
STANDARD_DEVIATION 0.622 • n=5 Participants
|
2.065 litres
STANDARD_DEVIATION 0.533 • n=7 Participants
|
2.089 litres
STANDARD_DEVIATION 0.683 • n=5 Participants
|
2.066 litres
STANDARD_DEVIATION 0.572 • n=4 Participants
|
2.053 litres
STANDARD_DEVIATION 0.628 • n=21 Participants
|
2.175 litres
STANDARD_DEVIATION 0.624 • n=8 Participants
|
2.078 litres
STANDARD_DEVIATION 0.612 • n=8 Participants
|
|
BDI focal scores at randomization
|
5.6 scores on a scale
STANDARD_DEVIATION 1.88 • n=5 Participants
|
5.9 scores on a scale
STANDARD_DEVIATION 1.87 • n=7 Participants
|
5.8 scores on a scale
STANDARD_DEVIATION 1.77 • n=5 Participants
|
5.8 scores on a scale
STANDARD_DEVIATION 1.63 • n=4 Participants
|
6.1 scores on a scale
STANDARD_DEVIATION 1.43 • n=21 Participants
|
5.7 scores on a scale
STANDARD_DEVIATION 1.59 • n=8 Participants
|
5.8 scores on a scale
STANDARD_DEVIATION 1.71 • n=8 Participants
|
|
CAT total score at randomization
|
19.6 scores on a scale
STANDARD_DEVIATION 5.60 • n=5 Participants
|
19.2 scores on a scale
STANDARD_DEVIATION 5.65 • n=7 Participants
|
19.2 scores on a scale
STANDARD_DEVIATION 5.83 • n=5 Participants
|
20.0 scores on a scale
STANDARD_DEVIATION 5.49 • n=4 Participants
|
19.3 scores on a scale
STANDARD_DEVIATION 5.73 • n=21 Participants
|
20.3 scores on a scale
STANDARD_DEVIATION 6.48 • n=8 Participants
|
19.6 scores on a scale
STANDARD_DEVIATION 5.80 • n=8 Participants
|
PRIMARY outcome
Timeframe: Baseline, Week 6Population: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Change from baseline in FEV1 AUC(0-12h), normalized by time, at the end of treatment (Week 6). Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 at Week 6 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (12 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-12h)=Mean FEV1 after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time;
Outcome measures
| Measure |
Treatment A
n=113 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=111 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=108 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=118 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=109 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=114 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in FEV1 AUC(0-12h) Normalized by Time at Week 6
|
0.070 Litres
Interval 0.034 to 0.106
|
0.118 Litres
Interval 0.082 to 0.155
|
0.153 Litres
Interval 0.116 to 0.19
|
0.147 Litres
Interval 0.111 to 0.183
|
0.002 Litres
Interval -0.035 to 0.039
|
0.213 Litres
Interval 0.177 to 0.25
|
SECONDARY outcome
Timeframe: Baseline, Day 1Population: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Change from baseline in FEV1 AUC(0-12h), normalized by time, on Day 1. Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 on Day 1 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (12 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-12h)=Mean FEV1 after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time;
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=120 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=121 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=122 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in FEV1 AUC(0-12h) Normalized by Time on Day 1
|
0.067 Litres
Interval 0.041 to 0.093
|
0.086 Litres
Interval 0.06 to 0.111
|
0.135 Litres
Interval 0.109 to 0.161
|
0.149 Litres
Interval 0.123 to 0.175
|
0.009 Litres
Interval -0.017 to 0.035
|
0.192 Litres
Interval 0.166 to 0.218
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Week 6Population: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Change from baseline in FEV1 AUC(0-4h), normalized by time on Day 1 of treatment (Week 0). Spirometry, used to measure FEV1, was performed according to internationally accepted standards. The AUC for FEV1 on Day 1 and at Week 6 of treatment was calculated by using the linear trapezoidal rule, based on the changes in FEV1 from the baseline values, and divided by the observation time (4 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; FEV1 AUC(0-4h)=Mean FEV1 after inhalation, measured at prespecified times for up to 4-h observation period (0-4h), normalized by time;
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in FEV1 AUC(0-4h) Normalized by Time on Day 1 and at Week 6
Day 1
|
0.101 Litres
Interval 0.077 to 0.125
|
0.115 Litres
Interval 0.091 to 0.139
|
0.173 Litres
Interval 0.149 to 0.196
|
0.190 Litres
Interval 0.166 to 0.214
|
0.030 Litres
Interval 0.006 to 0.053
|
0.194 Litres
Interval 0.17 to 0.218
|
|
Change From Baseline in FEV1 AUC(0-4h) Normalized by Time on Day 1 and at Week 6
Week 6
|
0.116 Litres
Interval 0.078 to 0.154
|
0.157 Litres
Interval 0.118 to 0.195
|
0.198 Litres
Interval 0.159 to 0.237
|
0.204 Litres
Interval 0.167 to 0.242
|
0.024 Litres
Interval -0.015 to 0.062
|
0.253 Litres
Interval 0.215 to 0.291
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Week 6Population: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Change from baseline in FEV1 peak(0-4h) (L) on Day 1 and at Week 6. Peak FEV1 is defined as the maximum FEV1 observed in the first 4 hours after dose of study medication. Definitions: Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second; Peak(0-4h)=Maximum FEV1 between 0 and 4 h.
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in FEV1 Peak(0-4h) at Day 1 and Week 6
Week 6
|
0.212 Litres
Interval 0.171 to 0.253
|
0.255 Litres
Interval 0.214 to 0.296
|
0.305 Litres
Interval 0.263 to 0.346
|
0.301 Litres
Interval 0.26 to 0.341
|
0.143 Litres
Interval 0.102 to 0.185
|
0.356 Litres
Interval 0.315 to 0.397
|
|
Change From Baseline in FEV1 Peak(0-4h) at Day 1 and Week 6
Day 1
|
0.197 Litres
Interval 0.17 to 0.224
|
0.211 Litres
Interval 0.183 to 0.238
|
0.260 Litres
Interval 0.233 to 0.287
|
0.288 Litres
Interval 0.261 to 0.315
|
0.136 Litres
Interval 0.109 to 0.163
|
0.299 Litres
Interval 0.272 to 0.326
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Week 6Population: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Change from baseline in FVC AUC(0-12h), normalized by time, on Day 1 and at the end of treatment (Week 6). Spirometry, used to measure FVC, was performed according to internationally accepted standards. The AUC for FVC was calculated by using the linear trapezoidal rule, based on the changes in FVC from the baseline values, and divided by the observation time (4 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; FVC AUC(0-12h)=Mean FVC after inhalation, measured at prespecified times for up to 12-h observation period (0-12 h), normalized by time;
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in FVC AUC(0-12h), Normalized by Time on Day 1 and at Week 6
Day 1
|
0.086 Litres
Interval 0.039 to 0.133
|
0.133 Litres
Interval 0.086 to 0.18
|
0.195 Litres
Interval 0.148 to 0.242
|
0.220 Litres
Interval 0.173 to 0.267
|
0.011 Litres
Interval -0.036 to 0.058
|
0.305 Litres
Interval 0.258 to 0.351
|
|
Change From Baseline in FVC AUC(0-12h), Normalized by Time on Day 1 and at Week 6
Week 6
|
0.084 Litres
Interval 0.026 to 0.142
|
0.145 Litres
Interval 0.087 to 0.203
|
0.190 Litres
Interval 0.131 to 0.249
|
0.184 Litres
Interval 0.127 to 0.241
|
-0.029 Litres
Interval -0.087 to 0.03
|
0.298 Litres
Interval 0.24 to 0.355
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Week 6Population: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Change from baseline in FVC AUC(0-4h), normalized by time, on Day 1 and at the end of treatment (Week 6). Spirometry, used to measure FVC, was performed according to internationally accepted standards. The AUC for FVC was calculated by using the linear trapezoidal rule, based on the changes in FVC from the baseline values, and divided by the observation time (4 hours). Definitions: AUC=Area under the curve; Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; FVC AUC(0-4)=Mean FVC after inhalation, measured at prespecified times for up to 4-h observation period (0-4 h), normalized by time;
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in FVC AUC(0-4h) Normalized by Time on Day 1 and at Week 6
Day 1
|
0.133 Litres
Interval 0.087 to 0.179
|
0.192 Litres
Interval 0.146 to 0.238
|
0.244 Litres
Interval 0.198 to 0.29
|
0.273 Litres
Interval 0.227 to 0.319
|
0.036 Litres
Interval -0.01 to 0.082
|
0.311 Litres
Interval 0.266 to 0.357
|
|
Change From Baseline in FVC AUC(0-4h) Normalized by Time on Day 1 and at Week 6
Week 6
|
0.149 Litres
Interval 0.089 to 0.21
|
0.203 Litres
Interval 0.143 to 0.264
|
0.248 Litres
Interval 0.187 to 0.309
|
0.253 Litres
Interval 0.194 to 0.313
|
0.000 Litres
Interval -0.062 to 0.061
|
0.353 Litres
Interval 0.293 to 0.413
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Week 6Population: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Change from baseline in FVC peak(0-4h) (L) on Day 1 and at the end of treatment at Week 6. Peak FEV1 is defined as the maximum FEV1 observed in the first 4 hours after dose of study medication. Definitions: Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); Day 1=Day of the first dose of randomized study drug at Visit 2 (Week 0); FVC=Forced Vital Capacity; Peak(0-4h)=Maximum FEV1 between 0 and 4 h.
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in FVC Peak(0-4h) on Day 1 and at Week 6
Day 1
|
0.293 Litres
Interval 0.241 to 0.345
|
0.372 Litres
Interval 0.32 to 0.423
|
0.414 Litres
Interval 0.362 to 0.466
|
0.455 Litres
Interval 0.403 to 0.506
|
0.213 Litres
Interval 0.161 to 0.266
|
0.491 Litres
Interval 0.439 to 0.542
|
|
Change From Baseline in FVC Peak(0-4h) on Day 1 and at Week 6
Week 6
|
0.322 Litres
Interval 0.258 to 0.386
|
0.379 Litres
Interval 0.315 to 0.443
|
0.431 Litres
Interval 0.366 to 0.495
|
0.427 Litres
Interval 0.364 to 0.49
|
0.182 Litres
Interval 0.117 to 0.247
|
0.530 Litres
Interval 0.467 to 0.594
|
SECONDARY outcome
Timeframe: Day 1Population: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Time to onset of action is defined as the time (in minutes) from receiving the study drug on Day 1, until the FEV1 change from baseline is ≥100 mL.
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Time to Onset of Action (Change From Baseline in Post-dose FEV1 ≥ 100 mL) on Day 1
|
45.1 minutes
Interval 34.5 to 66.2
|
32.6 minutes
Interval 30.7 to 45.6
|
29.5 minutes
Interval 16.3 to 30.8
|
27.3 minutes
Interval 16.5 to 30.5
|
240.1 minutes
Interval 179.6 to 361.8
|
28.1 minutes
Interval 18.0 to 32.1
|
SECONDARY outcome
Timeframe: Day 1Population: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Number of patients achieving onset of action was defined as a change from baseline in post-dose FEV1 ≥100 mL on Day 1. These are the patients who contributed to the results, reported as median and 95% CI for 'time to onset of action' presented in Outcome Measure 8, above.
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Number of Patients Achieving Onset of Action - Change From Baseline in Post-dose FEV1 ≥100 mL on Day 1
|
90 Participants
|
103 Participants
|
103 Participants
|
110 Participants
|
74 Participants
|
113 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 3, Week 6Population: Intention to treat All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Change from baseline in FEV1 at treatment visit 3 (Week 3) and treatment visit 4 (Week 6) of treatment. Spirometry, used to measure FEV1, was performed according to internationally accepted standards. Definitions: Baseline=Baseline value was the average of the pre-dose measurements (at 45 mins and 15 mins pre-dose), at Visit 2 (Week 0); FEV1=Forced expiratory volume in the 1st second;
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Pre-dose Morning FEV1 at Week 3 and Week 6
Week 3
|
0.059 Litres
Interval 0.025 to 0.092
|
0.080 Litres
Interval 0.047 to 0.114
|
0.122 Litres
Interval 0.088 to 0.156
|
0.111 Litres
Interval 0.078 to 0.145
|
0.000 Litres
Interval -0.034 to 0.034
|
0.122 Litres
Interval 0.089 to 0.156
|
|
Change From Baseline in Pre-dose Morning FEV1 at Week 3 and Week 6
Week 6
|
0.020 Litres
Interval -0.018 to 0.058
|
0.088 Litres
Interval 0.05 to 0.126
|
0.107 Litres
Interval 0.068 to 0.145
|
0.130 Litres
Interval 0.093 to 0.168
|
-0.012 Litres
Interval -0.05 to 0.027
|
0.112 Litres
Interval 0.074 to 0.15
|
SECONDARY outcome
Timeframe: Baseline, Week 3, Week 6Population: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Change from baseline in IC at treatment Visit 3 (Week 3) and treatment Visit 4 (Week 6). Spirometry was used to measure IC and was performed according to internationally accepted standards. Definitions: Baseline: value of the measurement recorded at 45 mins pre-dose at Visit 2 (Week 0); IC=Inspiratory capacity;
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Pre-Dose Morning Inspiratory Capacity (IC) at Week 3 and Week 6
Week 3
|
0.156 Litres
Interval 0.09 to 0.222
|
0.137 Litres
Interval 0.071 to 0.203
|
0.106 Litres
Interval 0.04 to 0.172
|
0.140 Litres
Interval 0.074 to 0.205
|
0.047 Litres
Interval -0.02 to 0.113
|
0.090 Litres
Interval 0.024 to 0.156
|
|
Change From Baseline in Pre-Dose Morning Inspiratory Capacity (IC) at Week 3 and Week 6
Week 6
|
0.045 Litres
Interval -0.025 to 0.115
|
0.090 Litres
Interval 0.021 to 0.16
|
0.136 Litres
Interval 0.065 to 0.207
|
0.105 Litres
Interval 0.036 to 0.174
|
0.025 Litres
Interval -0.046 to 0.096
|
0.099 Litres
Interval 0.029 to 0.169
|
SECONDARY outcome
Timeframe: Baseline, Week 3, Week 6Population: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Number of subjects achieving TDI focal score ≥1, at treatment visit 3 (Week 3) and at treatment visit 4 (Week 6). TDI is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline established by the BDI questionnaire. TDI consists of the same 24 items and 3 domains as the BDI, with the same 2-week recall period. Each category is rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement); total score ranging from -9 to +9, with higher scores indicating better outcomes. The minimal clinically important differences (MCID) is considered a change of ≥1 unit. The same investigator or designee interviewed the subject for the BDI and TDI during the study period. A TDI focal score of ≥1 is considered as clinically important. Definitions: Baseline=The BDI focal score value at Visit 2 (Week 0); BDI=Baseline Dyspnea Index; MCID=Minimal Clinically Important Differences; TDI=Transition Dyspnea Index;
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Transition Dyspnea Index (TDI) Response (Focal Score ≥1) at Week 3 and Week 6
Week 3 Focal Score ≥ 1
|
70 Participants
|
78 Participants
|
75 Participants
|
84 Participants
|
67 Participants
|
74 Participants
|
|
Transition Dyspnea Index (TDI) Response (Focal Score ≥1) at Week 3 and Week 6
Week 6 Focal Score ≥ 1
|
74 Participants
|
83 Participants
|
82 Participants
|
91 Participants
|
55 Participants
|
80 Participants
|
SECONDARY outcome
Timeframe: Baseline, Week 3, Week 6Population: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Transitional Dyspnea Index (TDI) focal score at treatment visit 3 (Week 3) and treatment visit 4 (Week 6). TDI is a validated, interviewer-administered questionnaire that measures changes in dyspnea severity from the baseline established by the BDI questionnaire. TDI consists of the same 24 items and 3 domains as the BDI, with the same 2-week recall period. Each category is rated by 7 grades ranging from -3 (major deterioration) to +3 (major improvement), with a total score ranging from -9 to +9, with higher scores indicating better outcomes. The minimal clinically important differences (MCID) is considered a change of ≥1 unit. The same investigator or designee interviewed the subject for the BDI and TDI during the study period. A TDI focal score of ≥1 is considered as clinically important. Definitions: Baseline=The BDI focal score value at Visit 2 (Week 0); BDI=Baseline Dyspnea Index; MCID=Minimal Clinically Important Differences; TDI=Transition Dyspnea Index;
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Transition Dyspnea Index (TDI) Focal Score at Week 3 and Week 6
Week 3
|
1.29 score on a scale
Interval 0.82 to 1.75
|
1.55 score on a scale
Interval 1.09 to 2.01
|
1.54 score on a scale
Interval 1.07 to 2.01
|
1.94 score on a scale
Interval 1.47 to 2.4
|
1.14 score on a scale
Interval 0.67 to 1.61
|
1.66 score on a scale
Interval 1.2 to 2.13
|
|
Transition Dyspnea Index (TDI) Focal Score at Week 3 and Week 6
Week 6
|
1.65 score on a scale
Interval 1.18 to 2.11
|
2.02 score on a scale
Interval 1.55 to 2.48
|
2.05 score on a scale
Interval 1.58 to 2.52
|
2.55 score on a scale
Interval 2.09 to 3.01
|
1.03 score on a scale
Interval 0.56 to 1.51
|
2.11 score on a scale
Interval 1.65 to 2.58
|
SECONDARY outcome
Timeframe: Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment periodPopulation: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Evaluate the number of rescue medication-free days compared with baseline. Results are shown as percentage (%) of rescue medication-free days; an increased value indicates improvement from baseline. Definitions: Baseline=Data recorded during the run-in period (a 2-week period prior to randomization to study treatment and study drug intake); Inter-visit period 1=Starts at randomization to treatment (Visit 2, Week 0) and runs to the day before the subject returns to the clinic (Visit 3, Week 3); Inter-visit period 2=Starts when the subject returns to the clinic (Visit 3, Week 3) and runs to the end of the randomized treatment period (Visit 4, Week 6); Entire Treatment period=From day of randomization to drug intake to the end of the randomized treatment period (Visit 4, Week 6); Randomization=Randomization to study drug treatment (Visit 2, Week 0).
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Percentage of Rescue Medication-Free Days During Inter-Visit Periods and the Entire Treatment Period
Entire treatment period
|
15.30 % of of rescue medication-free days
Interval 10.61 to 20.0
|
15.59 % of of rescue medication-free days
Interval 10.93 to 20.25
|
14.79 % of of rescue medication-free days
Interval 10.07 to 19.5
|
18.17 % of of rescue medication-free days
Interval 13.49 to 22.86
|
7.98 % of of rescue medication-free days
Interval 3.25 to 12.72
|
12.39 % of of rescue medication-free days
Interval 7.45 to 17.32
|
|
Change From Baseline in Percentage of Rescue Medication-Free Days During Inter-Visit Periods and the Entire Treatment Period
Inter-visit period 1
|
16.78 % of of rescue medication-free days
Interval 12.02 to 21.54
|
15.67 % of of rescue medication-free days
Interval 10.96 to 20.39
|
15.55 % of of rescue medication-free days
Interval 10.79 to 20.31
|
18.19 % of of rescue medication-free days
Interval 13.44 to 22.94
|
8.90 % of of rescue medication-free days
Interval 4.12 to 13.68
|
13.51 % of of rescue medication-free days
Interval 8.52 to 18.5
|
|
Change From Baseline in Percentage of Rescue Medication-Free Days During Inter-Visit Periods and the Entire Treatment Period
Inter-visit period 2
|
13.83 % of of rescue medication-free days
Interval 8.69 to 18.97
|
15.51 % of of rescue medication-free days
Interval 10.4 to 20.62
|
14.03 % of of rescue medication-free days
Interval 8.83 to 19.23
|
18.15 % of of rescue medication-free days
Interval 13.04 to 23.27
|
7.07 % of of rescue medication-free days
Interval 1.87 to 12.27
|
11.27 % of of rescue medication-free days
Interval 5.85 to 16.69
|
SECONDARY outcome
Timeframe: Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment periodPopulation: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Evaluate the change from baseline in average use of rescue medication (number of puffs/day) during the inter-visit periods and the entire treatment period. Results are shown as number of puffs/day; a decrease (implies improvement) from baseline in average use of rescue medication. Definitions: Baseline=Data recorded during the run-in period (a 2-week period prior to randomization to study treatment and study drug intake); Inter-visit period 1=Starts at randomization to treatment (Visit 2, Week 0) and runs to the day before the subject returns to the clinic (Visit 3 (Week 3); Inter-visit period 2=Starts when the subject returns to the clinic (Visit 3, Week 3) and runs to the end of the randomized treatment period (Visit 4, Week 6); Entire Treatment period=From day of randomization to drug intake to the end of the randomized treatment period (Visit 4, Week 6); Randomization=Randomization to study drug treatment (Visit 2, Week 0);
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Average Use of Rescue Medication During Inter-Visit Periods and the Entire Treatment Period
Inter-visit period 1
|
-0.72 Number of puffs/day
Interval -0.9 to -0.55
|
-0.58 Number of puffs/day
Interval -0.75 to -0.41
|
-0.53 Number of puffs/day
Interval -0.7 to -0.35
|
-0.71 Number of puffs/day
Interval -0.89 to -0.54
|
-0.30 Number of puffs/day
Interval -0.47 to -0.12
|
-0.52 Number of puffs/day
Interval -0.7 to -0.34
|
|
Change From Baseline in Average Use of Rescue Medication During Inter-Visit Periods and the Entire Treatment Period
Inter-visit period 2
|
-0.59 Number of puffs/day
Interval -0.78 to -0.39
|
-0.50 Number of puffs/day
Interval -0.69 to -0.3
|
-0.51 Number of puffs/day
Interval -0.71 to -0.31
|
-0.69 Number of puffs/day
Interval -0.89 to -0.5
|
-0.17 Number of puffs/day
Interval -0.37 to 0.03
|
-0.40 Number of puffs/day
Interval -0.61 to -0.19
|
|
Change From Baseline in Average Use of Rescue Medication During Inter-Visit Periods and the Entire Treatment Period
Entire treatment period
|
-0.66 Number of puffs/day
Interval -0.83 to -0.48
|
-0.54 Number of puffs/day
Interval -0.71 to -0.37
|
-0.52 Number of puffs/day
Interval -0.7 to -0.34
|
-0.70 Number of puffs/day
Interval -0.88 to -0.53
|
-0.23 Number of puffs/day
Interval -0.41 to -0.06
|
-0.46 Number of puffs/day
Interval -0.64 to -0.28
|
SECONDARY outcome
Timeframe: Baseline, Inter-visit period 1, Inter-visit period 2, Entire treatment periodPopulation: Intention to treat: All randomized patients who received at least one dose of the study treatment and with at least one available evaluation of efficacy after baseline (primary or secondary efficacy variables).
Change from baseline in average EXACT-Respiratory Symptom (E-RS) total score during inter-visit periods and the entire treatment period E-RS in COPD uses 11 respiratory symptom items from the 14-item EXAcerbations of COPD tool (EXACT). E-RS total score quantifies respiratory symptom severity on a scale ranging from 0 to 40. Higher E-RS total scores indicate more severe symptoms and a declining total score indicates health improvement. E-RS questionnaire was completed by the patient each evening (e-diary). Definitions: For details on baseline, inter-visit periods, and the entire treatment period, please refer to outcome measure #15.
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in Average EXACT-Respiratory Symptom (E-RS) Total Score During Inter-Visit Periods and the Entire Treatment Period
Entire treatment period
|
-1.855 score on a scale
Interval -2.433 to -1.278
|
-1.689 score on a scale
Interval -2.262 to -1.116
|
-2.044 score on a scale
Interval -2.624 to -1.464
|
-1.870 score on a scale
Interval -2.445 to -1.295
|
-0.698 score on a scale
Interval -1.28 to -0.115
|
-1.393 score on a scale
Interval -2.001 to -0.784
|
|
Change From Baseline in Average EXACT-Respiratory Symptom (E-RS) Total Score During Inter-Visit Periods and the Entire Treatment Period
Inter-visit period 1
|
-1.681 score on a scale
Interval -2.236 to -1.127
|
-1.539 score on a scale
Interval -2.087 to -0.99
|
-1.941 score on a scale
Interval -2.495 to -1.388
|
-1.663 score on a scale
Interval -2.215 to -1.111
|
-0.714 score on a scale
Interval -1.272 to -0.157
|
-1.280 score on a scale
Interval -1.862 to -0.698
|
|
Change From Baseline in Average EXACT-Respiratory Symptom (E-RS) Total Score During Inter-Visit Periods and the Entire Treatment Period
Inter-visit period 2
|
-2.030 score on a scale
Interval -2.694 to -1.365
|
-1.840 score on a scale
Interval -2.499 to -1.18
|
-2.147 score on a scale
Interval -2.818 to -1.475
|
-2.077 score on a scale
Interval -2.737 to -1.417
|
-0.681 score on a scale
Interval -1.353 to -0.009
|
-1.505 score on a scale
Interval -2.206 to -0.803
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Week 6Population: Safety population: All randomized patients who received at least one dose of study treatment.
Vital signs -- Systolic blood pressure (SBP), Diastolic blood pressure (DBP) were measured at prespecified times, using a 12-Lead single ECGs were recorded at all study visits (pre-dose at V1 (Week -2) and V3 (Week 3), as well as at pre-dose and 1.5 hours post-dose at Visit 2 (Week 0) and Visit 4 (Week 6). Results are shown by treatment group, as change from baseline (in mmHg) for representative timepoints. Definitions: Baseline=Values recorded pre-dose (Visit 2, Week 0); Day 1=Day of the first dose of randomized study drug (Visit 2, Week 0);
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
DBP, Day 1, 30 min post dose
|
-0.7 mmHg
Interval -21.0 to 14.0
|
-0.6 mmHg
Interval -15.0 to 15.0
|
-2.1 mmHg
Interval -20.0 to 11.0
|
-1.4 mmHg
Interval -28.0 to 17.0
|
-0.8 mmHg
Interval -15.0 to 12.0
|
0.1 mmHg
Interval -27.0 to 22.0
|
|
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
SBP, Day 1, 11 h post dose
|
1.1 mmHg
Interval -27.0 to 34.0
|
2.0 mmHg
Interval -25.0 to 39.0
|
-0.0 mmHg
Interval -34.0 to 34.0
|
1.7 mmHg
Interval -26.0 to 39.0
|
1.9 mmHg
Interval -35.0 to 56.0
|
0.9 mmHg
Interval -25.0 to 48.0
|
|
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
SBP, Day 1, 30 min post dose
|
-1.4 mmHg
Interval -31.0 to 25.0
|
-0.4 mmHg
Interval -24.0 to 24.0
|
-2.0 mmHg
Interval -31.0 to 24.0
|
-1.9 mmHg
Interval -32.0 to 34.0
|
-0.9 mmHg
Interval -25.0 to 26.0
|
-1.2 mmHg
Interval -32.0 to 30.0
|
|
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
SBP, Day 1, 1,5 h post dose
|
0.3 mmHg
Interval -33.0 to 24.0
|
-1.1 mmHg
Interval -29.0 to 36.0
|
-0.6 mmHg
Interval -33.0 to 24.0
|
-1.8 mmHg
Interval -34.0 to 22.0
|
0.2 mmHg
Interval -25.0 to 33.0
|
-1.5 mmHg
Interval -30.0 to 34.0
|
|
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
DBP, Day 1, 1,5 h post dose
|
-0.7 mmHg
Interval -20.0 to 17.0
|
-1.8 mmHg
Interval -22.0 to 20.0
|
-1.7 mmHg
Interval -23.0 to 13.0
|
-1.6 mmHg
Interval -31.0 to 17.0
|
-1.7 mmHg
Interval -18.0 to 14.0
|
-1.5 mmHg
Interval -23.0 to 23.0
|
|
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
DBP, Day 1, 11 h post dose
|
-0.9 mmHg
Interval -20.0 to 17.0
|
0.3 mmHg
Interval -18.0 to 21.0
|
-1.6 mmHg
Interval -27.0 to 17.0
|
-1.4 mmHg
Interval -18.0 to 20.0
|
-1.0 mmHg
Interval -25.0 to 22.0
|
-1.2 mmHg
Interval -19.0 to 27.0
|
|
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
SBP, Week 6, pre-dose
|
0.4 mmHg
Interval -34.0 to 31.0
|
0.8 mmHg
Interval -50.0 to 34.0
|
0.4 mmHg
Interval -27.0 to 47.0
|
-1.0 mmHg
Interval -36.0 to 47.0
|
1.6 mmHg
Interval -32.0 to 46.0
|
1.3 mmHg
Interval -33.0 to 63.0
|
|
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
DBP, Week 6, pre-dose
|
0.4 mmHg
Interval -32.0 to 25.0
|
0.5 mmHg
Interval -23.0 to 21.0
|
-0.3 mmHg
Interval -16.0 to 18.0
|
-1.0 mmHg
Interval -28.0 to 25.0
|
0.0 mmHg
Interval -26.0 to 18.0
|
-0.2 mmHg
Interval -30.0 to 20.0
|
|
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
SBP, Week 6, 30 min post dose
|
-1.6 mmHg
Interval -35.0 to 27.0
|
-0.9 mmHg
Interval -62.0 to 39.0
|
-0.5 mmHg
Interval -34.0 to 42.0
|
-2.5 mmHg
Interval -41.0 to 35.0
|
0.5 mmHg
Interval -30.0 to 42.0
|
0.1 mmHg
Interval -35.0 to 54.0
|
|
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
DBP, Week 6, 30 min post dose
|
-0.7 mmHg
Interval -24.0 to 21.0
|
-0.9 mmHg
Interval -28.0 to 19.0
|
-1.5 mmHg
Interval -24.0 to 19.0
|
-2.0 mmHg
Interval -25.0 to 22.0
|
-0.8 mmHg
Interval -24.0 to 24.0
|
-1.2 mmHg
Interval -26.0 to 24.0
|
|
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
SBP, Week 6, 1,5 h post dose
|
-1.3 mmHg
Interval -32.0 to 31.0
|
-0.6 mmHg
Interval -31.0 to 36.0
|
-0.5 mmHg
Interval -34.0 to 47.0
|
-2.3 mmHg
Interval -42.0 to 40.0
|
0.1 mmHg
Interval -34.0 to 49.0
|
0.5 mmHg
Interval -34.0 to 67.0
|
|
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
DBP, Week 6, 1,5 h post dose
|
-1.0 mmHg
Interval -28.0 to 21.0
|
-2.7 mmHg
Interval -28.0 to 16.0
|
-2.0 mmHg
Interval -21.0 to 17.0
|
-2.3 mmHg
Interval -30.0 to 22.0
|
-1.1 mmHg
Interval -31.0 to 19.0
|
-0.6 mmHg
Interval -28.0 to 33.0
|
|
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
SBP, Week 6, 11 h post dose
|
0.2 mmHg
Interval -38.0 to 36.0
|
1.5 mmHg
Interval -26.0 to 36.0
|
0.5 mmHg
Interval -31.0 to 53.0
|
2.2 mmHg
Interval -37.0 to 53.0
|
3.2 mmHg
Interval -25.0 to 66.0
|
2.0 mmHg
Interval -26.0 to 45.0
|
|
Vital Signs -- Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP)
DBP, Week 6, 11 h post dose
|
-0.9 mmHg
Interval -24.0 to 21.0
|
-2.0 mmHg
Interval -27.0 to 19.0
|
-2.3 mmHg
Interval -25.0 to 25.0
|
-1.4 mmHg
Interval -27.0 to 21.0
|
-1.0 mmHg
Interval -27.0 to 20.0
|
-0.7 mmHg
Interval -17.0 to 21.0
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Week 6Population: Safety population: All randomized patients who received at least one dose of study treatment.
Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - Heart rate (HR) Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5m, +55m, and at +2.5 h.
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Heart Rate (HR)
HR, Day 1, 5 min post dose
|
-8.85 bpm
Interval -57.3 to 16.3
|
-6.62 bpm
Interval -53.7 to 22.3
|
-7.78 bpm
Interval -44.0 to 14.3
|
-7.64 bpm
Interval -41.3 to 19.0
|
-4.84 bpm
Interval -39.7 to 31.7
|
-5.54 bpm
Interval -34.3 to 24.3
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Heart Rate (HR)
HR, Day before Week 6, 2.5 h post dose
|
-2.30 bpm
Interval -48.0 to 22.3
|
-0.01 bpm
Interval -58.3 to 44.3
|
-1.13 bpm
Interval -39.3 to 26.3
|
-0.73 bpm
Interval -42.0 to 39.7
|
2.49 bpm
Interval -35.7 to 43.7
|
-1.47 bpm
Interval -34.7 to 44.0
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Heart Rate (HR)
HR, Day 1, 55 min post dose
|
-7.19 bpm
Interval -45.7 to 12.0
|
-8.29 bpm
Interval -33.3 to 10.3
|
-8.28 bpm
Interval -40.0 to 27.7
|
-9.59 bpm
Interval -74.0 to 17.3
|
-7.44 bpm
Interval -49.3 to 36.3
|
-7.19 bpm
Interval -41.3 to 37.7
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Heart Rate (HR)
HR, Day 1, 2.5 h post dose
|
-7.57 bpm
Interval -51.7 to 19.3
|
-6.75 bpm
Interval -51.0 to 16.7
|
-9.20 bpm
Interval -46.7 to 26.7
|
-7.46 bpm
Interval -94.7 to 21.0
|
-6.12 bpm
Interval -45.7 to 30.3
|
-8.96 bpm
Interval -40.0 to 18.0
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Heart Rate (HR)
HR, Day before Week 6, 5 min post dose
|
-1.72 bpm
Interval -56.3 to 34.3
|
-1.06 bpm
Interval -47.0 to 44.3
|
-1.61 bpm
Interval -37.0 to 30.3
|
-1.85 bpm
Interval -31.3 to 36.0
|
3.92 bpm
Interval -31.3 to 47.0
|
1.70 bpm
Interval -28.7 to 25.7
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Heart Rate (HR)
HR, Day before Week 6, 55 min post dose
|
-1.52 bpm
Interval -40.7 to 33.0
|
0.41 bpm
Interval -30.0 to 33.0
|
-1.10 bpm
Interval -37.3 to 49.3
|
-1.40 bpm
Interval -77.7 to 25.0
|
1.12 bpm
Interval -41.3 to 44.2
|
1.22 bpm
Interval -25.3 to 36.7
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Week 6Population: Safety population: All randomized patients who received at least one dose of study treatment.
Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - PR Interval Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values were recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h.
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - PR Interval
PR Interval, Day 1, 55 min post dose
|
7.20 msec
Interval -23.0 to 59.7
|
6.89 msec
Interval -24.3 to 120.7
|
8.21 msec
Interval -26.7 to 42.3
|
6.77 msec
Interval -20.0 to 49.3
|
4.38 msec
Interval -35.7 to 36.0
|
4.77 msec
Interval -32.7 to 40.0
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - PR Interval
PR Interval, Day 1, 2.5 h post dose
|
8.48 msec
Interval -20.3 to 77.7
|
9.38 msec
Interval -37.0 to 131.3
|
7.58 msec
Interval -18.7 to 91.3
|
6.16 msec
Interval -22.0 to 47.3
|
5.84 msec
Interval -27.0 to 38.7
|
4.25 msec
Interval -36.7 to 40.7
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - PR Interval
PR Interval, Day before Week 6, 55 min post dose
|
0.88 msec
Interval -47.3 to 32.3
|
2.37 msec
Interval -53.7 to 38.7
|
1.91 msec
Interval -76.3 to 37.7
|
0.82 msec
Interval -33.3 to 50.0
|
-1.13 msec
Interval -46.0 to 48.3
|
-1.66 msec
Interval -48.0 to 25.0
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - PR Interval
PR Interval, Day before Week 6, 2.5 h post dose
|
2.50 msec
Interval -38.7 to 40.0
|
3.01 msec
Interval -54.7 to 76.0
|
0.16 msec
Interval -59.0 to 81.0
|
0.84 msec
Interval -30.0 to 61.7
|
-1.22 msec
Interval -59.0 to 47.7
|
-1.94 msec
Interval -47.0 to 55.3
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - PR Interval
PR Interval, Day 1, 5 min post dose
|
7.24 msec
Interval -23.0 to 54.7
|
6.53 msec
Interval -17.3 to 48.3
|
6.08 msec
Interval -36.0 to 37.3
|
6.71 msec
Interval -14.3 to 41.7
|
3.06 msec
Interval -20.7 to 33.7
|
4.90 msec
Interval -18.3 to 30.7
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - PR Interval
PR Interval, Day before Week 6, 5 min post dose
|
0.44 msec
Interval -27.7 to 39.3
|
1.36 msec
Interval -30.0 to 59.0
|
-0.11 msec
Interval -54.3 to 26.7
|
3.88 msec
Interval -33.3 to 204.0
|
-1.36 msec
Interval -48.3 to 31.7
|
0.82 msec
Interval -23.3 to 37.2
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Week 6Population: Safety population: All randomized patients who received at least one dose of study treatment.
Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - QRS Interval Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values were recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h.
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - QRS Interval
QRS Interval, Day before Week 6, 5 min post dose
|
0.61 msec
Interval -23.3 to 34.0
|
-1.76 msec
Interval -76.0 to 17.3
|
0.43 msec
Interval -15.0 to 13.3
|
2.00 msec
Interval -8.7 to 67.3
|
0.45 msec
Interval -22.3 to 44.3
|
0.69 msec
Interval -17.0 to 17.5
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - QRS Interval
QRS Interval, Day before Week 6, 55 min post dose
|
1.12 msec
Interval -10.7 to 29.3
|
-0.09 msec
Interval -76.7 to 30.0
|
0.85 msec
Interval -18.3 to 13.7
|
2.38 msec
Interval -10.7 to 62.3
|
0.77 msec
Interval -16.0 to 53.7
|
0.42 msec
Interval -20.3 to 17.7
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - QRS Interval
QRS Interval, Day before Week 6, 2.5 h post dose
|
1.49 msec
Interval -14.0 to 40.0
|
0.74 msec
Interval -73.0 to 25.0
|
0.30 msec
Interval -18.3 to 24.0
|
2.18 msec
Interval -18.2 to 59.3
|
1.14 msec
Interval -14.7 to 43.7
|
1.35 msec
Interval -15.7 to 27.0
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - QRS Interval
QRS Interval, Day 1, 5 min post dose
|
1.18 msec
Interval -15.0 to 14.7
|
0.05 msec
Interval -17.7 to 16.7
|
1.50 msec
Interval -12.0 to 17.7
|
1.99 msec
Interval -6.0 to 16.7
|
0.45 msec
Interval -13.0 to 20.3
|
1.50 msec
Interval -14.0 to 13.0
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - QRS Interval
QRS Interval, Day 1, 55 min post dose
|
0.97 msec
Interval -16.3 to 15.0
|
1.19 msec
Interval -18.0 to 31.0
|
1.21 msec
Interval -14.7 to 20.0
|
1.56 msec
Interval -11.0 to 14.7
|
0.14 msec
Interval -13.7 to 13.7
|
1.70 msec
Interval -13.3 to 16.3
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - QRS Interval
QRS Interval, Day 1, 2.5 h post dose
|
1.38 msec
Interval -14.0 to 15.0
|
2.40 msec
Interval -15.3 to 23.7
|
1.80 msec
Interval -23.0 to 17.3
|
1.50 msec
Interval -17.8 to 27.3
|
0.64 msec
Interval -10.3 to 20.8
|
0.86 msec
Interval -20.7 to 18.7
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Week 6Population: Safety population: All randomized patients who received at least one dose of study treatment.
Change from baseline in 24-Hour Holter electrocardiogram (ECG) parameters - Fridericia-corrected QT interval (QTcF). Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h.
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Fridericia-corrected QT Interval (QTcF)
QTcF, Day 1, 55 min post dose
|
8.37 msec
Interval -35.3 to 47.0
|
5.41 msec
Interval -52.3 to 45.0
|
6.72 msec
Interval -43.7 to 40.7
|
9.90 msec
Interval -20.3 to 67.7
|
6.04 msec
Interval -34.7 to 61.3
|
5.43 msec
Interval -24.7 to 42.5
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Fridericia-corrected QT Interval (QTcF)
QTcF, Day 1, 2.5 h post dose
|
7.15 msec
Interval -31.3 to 38.0
|
8.65 msec
Interval -25.3 to 58.0
|
7.20 msec
Interval -22.3 to 36.3
|
5.45 msec
Interval -27.7 to 100.0
|
4.81 msec
Interval -75.7 to 61.3
|
6.77 msec
Interval -38.3 to 48.3
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Fridericia-corrected QT Interval (QTcF)
QTcF, Day before Week 6, 5 min post dose
|
1.61 msec
Interval -44.3 to 35.7
|
1.14 msec
Interval -70.7 to 76.3
|
-0.60 msec
Interval -30.3 to 30.0
|
1.67 msec
Interval -26.3 to 57.2
|
-3.56 msec
Interval -40.0 to 26.7
|
1.41 msec
Interval -26.7 to 58.0
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Fridericia-corrected QT Interval (QTcF)
QTcF, Day before Week 6, 55 min post dose
|
2.38 msec
Interval -28.7 to 45.0
|
0.09 msec
Interval -45.0 to 30.0
|
1.41 msec
Interval -65.0 to 40.7
|
4.15 msec
Interval -32.7 to 47.3
|
1.02 msec
Interval -22.7 to 32.7
|
3.19 msec
Interval -30.3 to 63.5
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Fridericia-corrected QT Interval (QTcF)
QTcF, Day before Week 6, 2.5 h post dose
|
4.13 msec
Interval -32.7 to 40.7
|
0.85 msec
Interval -64.0 to 51.7
|
-0.97 msec
Interval -55.3 to 48.3
|
1.73 msec
Interval -44.0 to 49.3
|
0.14 msec
Interval -31.0 to 33.7
|
2.50 msec
Interval -29.3 to 44.0
|
|
Change From Baseline in 24-Hour Holter Electrocardiogram (ECG) Parameters - Fridericia-corrected QT Interval (QTcF)
QTcF, Day 1, 5 min post dose
|
3.62 msec
Interval -38.0 to 39.7
|
5.37 msec
Interval -48.7 to 55.7
|
6.81 msec
Interval -34.0 to 39.7
|
6.25 msec
Interval -30.3 to 52.7
|
3.59 msec
Interval -33.3 to 50.3
|
5.56 msec
Interval -21.7 to 53.3
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Week 6Population: Safety population: All randomized patients who received at least one dose of study treatment.
24-hour Holter ECG - Prolonged QTcF - Male subjects. Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h.
Outcome measures
| Measure |
Treatment A
n=63 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=55 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=54 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=58 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=69 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=66 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day -1, 5 min · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day -1, 55 min · Actual value > 480 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day -1, 55 min · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day -1, 55 min · No prolongation (> 450 msec or > 480 msec or > 500 msec)
|
62 Participants
|
54 Participants
|
53 Participants
|
55 Participants
|
68 Participants
|
63 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day -1, 2.5 h · Actual value > 450 msec
|
1 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day -1, 2.5 h · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Any post dose time point · No prolongation (> 450 msec or > 480 msec or > 500 msec)
|
59 Participants
|
51 Participants
|
47 Participants
|
54 Participants
|
67 Participants
|
58 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day 1, 5 min post dose · No prolongation (> 450 msec or > 480 msec or > 500 msec)
|
60 Participants
|
53 Participants
|
51 Participants
|
55 Participants
|
68 Participants
|
61 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day 1, 55 min post dose · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day 1, 55 min post dose · No prolongation (> 450 msec or > 480 msec or > 500 msec)
|
60 Participants
|
53 Participants
|
50 Participants
|
55 Participants
|
68 Participants
|
61 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day 1, 2.5 h post dose · Actual value > 450 msec
|
3 Participants
|
3 Participants
|
3 Participants
|
2 Participants
|
1 Participants
|
4 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day 1, 2.5 h post dose · Actual value > 480 msec
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day 1, 2.5 h post dose · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day 1, 2.5 h post dose · No prolongation (> 450 msec or > 480 msec or > 500 msec)
|
59 Participants
|
52 Participants
|
51 Participants
|
56 Participants
|
68 Participants
|
62 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day before Week 6, 5 min post dose · Actual value > 450 msec
|
3 Participants
|
1 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
2 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day before Week 6, 5 min post dose · Actual value > 480 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day before Week 6, 5 min post dose · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day before Week 6, 5 min post dose · No prolongation (> 450 msec or > 480 msec or > 500 msec)
|
60 Participants
|
54 Participants
|
54 Participants
|
55 Participants
|
69 Participants
|
63 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day before Week 6, 55 min post dose · Actual value > 450 msec
|
2 Participants
|
2 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
3 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day before Week 6, 55 min post dose · Actual value > 480 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day before Week 6, 55 min post dose · No prolongation (> 450 msec or > 480 msec or > 500 msec)
|
61 Participants
|
53 Participants
|
52 Participants
|
56 Participants
|
69 Participants
|
62 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day before Week 6, 2.5 h post dose · Actual value > 450 msec
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
3 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day before Week 6, 2.5 h post dose · Actual value > 480 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day before Week 6, 2.5 h post dose · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day before Week 6, 2.5 h post dose · No prolongation (> 450 msec or > 480 msec or > 500 msec)
|
62 Participants
|
54 Participants
|
54 Participants
|
57 Participants
|
69 Participants
|
63 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day -1, 5 min · Actual value > 450 msec
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day -1, 5 min · Actual value > 480 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day -1, 5 min · No prolongation (> 450 msec or > 480 msec or > 500 msec)
|
62 Participants
|
55 Participants
|
54 Participants
|
57 Participants
|
67 Participants
|
65 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day -1, 55 min · Actual value > 450 msec
|
1 Participants
|
1 Participants
|
1 Participants
|
3 Participants
|
1 Participants
|
3 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day -1, 2.5 h · Actual value > 480 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day -1, 2.5 h · No prolongation (> 450 msec or > 480 msec or > 500 msec)
|
62 Participants
|
54 Participants
|
54 Participants
|
56 Participants
|
66 Participants
|
66 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Any post dose time point · Actual value > 450 msec
|
3 Participants
|
4 Participants
|
6 Participants
|
4 Participants
|
2 Participants
|
5 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Any post dose time point · Actual value > 480 msec
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
3 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Any post dose time point · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day 1, 5 min post dose · Actual value > 450 msec
|
2 Participants
|
2 Participants
|
3 Participants
|
3 Participants
|
1 Participants
|
4 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day 1, 5 min post dose · Actual value > 480 msec
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day 1, 5 min post dose · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day 1, 55 min post dose · Actual value > 450 msec
|
2 Participants
|
2 Participants
|
3 Participants
|
3 Participants
|
1 Participants
|
4 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day 1, 55 min post dose · Actual value > 480 msec
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Male Subjects
QTcF, Day before Week 6, 55 min post dose · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Week 6Population: Safety population: All randomized patients who received at least one dose of study treatment.
24-hour Holter ECG - Prolonged QTcF - Female subjects. Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h.
Outcome measures
| Measure |
Treatment A
n=58 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=68 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=67 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=65 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=52 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=57 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day before Week 6, 55 min post dose · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day before Week 6, 55 min post dose · No prolongation (> 470 msec or > 500 msec)
|
58 Participants
|
66 Participants
|
67 Participants
|
65 Participants
|
52 Participants
|
57 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day -1, 5 min · Actual value > 470 msec
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day -1, 55 min · Actual value > 470 msec
|
1 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day -1, 55 min · Actual value > 500 msec
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day -1, 55 min · No prolongation (> 470 msec or > 500 msec)
|
57 Participants
|
64 Participants
|
67 Participants
|
64 Participants
|
52 Participants
|
57 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day -1, 2.5 h · Actual value > 470 msec
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day -1, 2.5 h · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day -1, 2.5 h · No prolongation (> 470 msec or > 500 msec)
|
57 Participants
|
66 Participants
|
67 Participants
|
65 Participants
|
52 Participants
|
57 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Any post dose time point · Actual value > 470 msec
|
3 Participants
|
3 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Any post dose time point · Actual value > 500 msec
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Any post dose time point · No prolongation (> 470 msec or > 500 msec)
|
55 Participants
|
64 Participants
|
67 Participants
|
64 Participants
|
52 Participants
|
56 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day 1, 5 min post dose · Actual value > 470 msec
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day 1, 5 min post dose · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day 1, 5 min post dose · No prolongation (> 470 msec or > 500 msec)
|
57 Participants
|
66 Participants
|
67 Participants
|
65 Participants
|
52 Participants
|
57 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day 1, 55 min post dose · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day 1, 55 min post dose · No prolongation (> 470 msec or > 500 msec)
|
56 Participants
|
65 Participants
|
67 Participants
|
65 Participants
|
52 Participants
|
57 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day before Week 6, 5 min post dose · Actual value > 470 msec
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day before Week 6, 5 min post dose · No prolongation (> 470 msec or > 500 msec)
|
57 Participants
|
66 Participants
|
67 Participants
|
65 Participants
|
52 Participants
|
57 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day before Week 6, 55 min post dose · Actual value > 470 msec
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day before Week 6, 2.5 h post dose · Actual value > 470 msec
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day before Week 6, 2.5 h post dose · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day before Week 6, 2.5 h post dose · No prolongation (> 470 msec or > 500 msec)
|
58 Participants
|
67 Participants
|
67 Participants
|
64 Participants
|
52 Participants
|
57 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day -1, 5 min · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day -1, 5 min · No prolongation (> 470 msec or > 500 msec)
|
58 Participants
|
67 Participants
|
67 Participants
|
65 Participants
|
52 Participants
|
57 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day 1, 55 min post dose · Actual value > 470 msec
|
2 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day 1, 2.5 h post dose · Actual value > 470 msec
|
1 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day 1, 2.5 h post dose · Actual value > 500 msec
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day 1, 2.5 h post dose · No prolongation (> 470 msec or > 500 msec)
|
57 Participants
|
65 Participants
|
67 Participants
|
65 Participants
|
52 Participants
|
56 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Female Subjects
QTcF, Day before Week 6, 5 min post dose · Actual value > 500 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Week 6Population: Safety population: All randomized patients who received at least one dose of study treatment.
24-hour Holter ECG - Prolonged QTcF - Change from baseline. Subjects had a 24-h Holter recording before and 24 h after the 1st dose of study drug (Visit 2) and for 24 h before the last dose of study drug (Visit 4). The time-matched values recorded during the 24 h before the 1st dose of study drug on Visit 2 and served as the baseline for the Holter-extracted ECG parameters. The time-averaged baseline score is the average of the Day -1 scores at +5 min, +55 min, and at +2.5 h. Results are presented as the number of subjects who had a change from baseline in QTcF of: \> 30 msec, \> 60 msec, and no prolongation (by \> 30 msec or \> 60 msec).
Outcome measures
| Measure |
Treatment A
n=121 Participants
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 Participants
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 Participants
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 Participants
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 Participants
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 Participants
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Any post dose time point · Change from baseline: > 30 msec
|
19 Participants
|
20 Participants
|
21 Participants
|
20 Participants
|
16 Participants
|
18 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Any post dose time point · Change from baseline: > 60 msec
|
0 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
1 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day 1, 5 min post dose · Change from baseline: > 60 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day 1, 5 min post dose · No change from baseline (> 30 msec or > 60 msec)
|
119 Participants
|
119 Participants
|
112 Participants
|
121 Participants
|
118 Participants
|
119 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day 1, 55 min post dose · Change from baseline: > 30 msec
|
8 Participants
|
4 Participants
|
5 Participants
|
6 Participants
|
4 Participants
|
5 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day 1, 2.5 h post dose · Change from baseline: > 30 msec
|
5 Participants
|
12 Participants
|
6 Participants
|
5 Participants
|
6 Participants
|
8 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day before Week 6, 2.5 h post dose · No change from baseline (> 30 msec or > 60 msec)
|
115 Participants
|
117 Participants
|
118 Participants
|
117 Participants
|
118 Participants
|
116 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day before Week 6, 2.5 h post dose · Change from baseline: > 60 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Any post dose time point · No change from baseline (> 30 msec or > 60 msec)
|
102 Participants
|
102 Participants
|
100 Participants
|
101 Participants
|
103 Participants
|
104 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day before Week 6, 5 min post dose · Change from baseline: > 60 msec
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day 1, 5 min post dose · Change from baseline: > 30 msec
|
2 Participants
|
4 Participants
|
9 Participants
|
2 Participants
|
3 Participants
|
4 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day 1, 55 min post dose · Change from baseline: > 60 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day 1, 55 min post dose · No change from baseline (> 30 msec or > 60 msec)
|
113 Participants
|
119 Participants
|
116 Participants
|
116 Participants
|
116 Participants
|
118 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day 1, 2.5 h post dose · Change from baseline: > 60 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day 1, 2.5 h post dose · No change from baseline (> 30 msec or > 60 msec)
|
116 Participants
|
111 Participants
|
115 Participants
|
117 Participants
|
114 Participants
|
115 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day before Week 6, 5 min post dose · Change from baseline: > 30 msec
|
5 Participants
|
3 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
3 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day before Week 6, 5 min post dose · No change from baseline (> 30 msec or > 60 msec)
|
116 Participants
|
119 Participants
|
121 Participants
|
120 Participants
|
121 Participants
|
120 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day before Week 6, 55 min post dose · Change from baseline: > 30 msec
|
5 Participants
|
0 Participants
|
7 Participants
|
7 Participants
|
3 Participants
|
4 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day before Week 6, 55 min post dose · Change from baseline: > 60 msec
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day before Week 6, 55 min post dose · No change from baseline (> 30 msec or > 60 msec)
|
116 Participants
|
123 Participants
|
114 Participants
|
116 Participants
|
118 Participants
|
118 Participants
|
|
24-hour Holter ECG - Prolonged QTcF - Change From Baseline
QTcF, Day before Week 6, 2.5 h post dose · Change from baseline: > 30 msec
|
6 Participants
|
6 Participants
|
3 Participants
|
6 Participants
|
3 Participants
|
7 Participants
|
Adverse Events
Treatment A
Serious events: 2 serious events
Other events: 16 other events
Deaths: 0 deaths
Treatment B
Serious events: 5 serious events
Other events: 14 other events
Deaths: 0 deaths
Treatment C
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Treatment D
Serious events: 1 serious events
Other events: 15 other events
Deaths: 0 deaths
Treatment E
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Treatment F
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment A
n=121 participants at risk
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 participants at risk
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 participants at risk
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 participants at risk
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 participants at risk
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 participants at risk
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
0.83%
1/121 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
|
Infections and infestations
Influenza
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.81%
1/123 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.81%
1/123 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.81%
1/123 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.81%
1/123 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer stage I
|
0.83%
1/121 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.81%
1/123 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.81%
1/123 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.81%
1/123 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.83%
1/121 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
|
Vascular disorders
Hypertension
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.83%
1/121 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
Other adverse events
| Measure |
Treatment A
n=121 participants at risk
CHF 5259 pMDI Dose 1, 12.5 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment B
n=123 participants at risk
CHF 5259 pMDI Dose 2, 25 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment C
n=121 participants at risk
CHF 5259 pMDI Dose 3, 50 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment D
n=123 participants at risk
CHF 5259 pMDI Dose 4, 100 μg TDD
CHF 5259 Dose Response: Test one of four different doses of CHF 5259
|
Treatment E
n=121 participants at risk
Placebo Control
Placebo: Placebo Control
|
Treatment F
n=123 participants at risk
Tiotropium Bromide inhalation powder, 18 µg TDD
Tiotropium Bromide Active Control, 18 µg Inhalation Capsule
|
|---|---|---|---|---|---|---|
|
Infections and infestations
Bronchitis
|
0.83%
1/121 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
3.3%
4/123 • Number of events 4 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.83%
1/121 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.81%
1/123 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
|
Infections and infestations
Upper respiratory tract infection
|
3.3%
4/121 • Number of events 4 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
1.6%
2/123 • Number of events 2 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
1.7%
2/121 • Number of events 2 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
4.1%
5/123 • Number of events 5 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
1.7%
2/121 • Number of events 2 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
2.4%
3/123 • Number of events 3 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
4.1%
5/123 • Number of events 5 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.83%
1/121 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.81%
1/123 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
2.5%
3/121 • Number of events 3 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
|
Nervous system disorders
Headache
|
4.1%
5/121 • Number of events 5 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
1.6%
2/123 • Number of events 2 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.83%
1/121 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
2.4%
3/123 • Number of events 3 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
1.7%
2/121 • Number of events 2 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.7%
2/121 • Number of events 2 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/123 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
2.5%
3/121 • Number of events 3 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
3.3%
4/123 • Number of events 4 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
3.3%
4/121 • Number of events 4 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
3.3%
4/123 • Number of events 4 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.3%
4/121 • Number of events 4 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.81%
1/123 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.81%
1/123 • Number of events 1 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
0.00%
0/121 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
1.6%
2/123 • Number of events 2 • From the first intake of study medication (visit 2, Week 0) until study completion (Visit 4, week 6) or discontinuation.
The safety population was used for the evaluation of treatment-emergent adverse event (TEAEs). The safety population is defined as all randomized patients who received at least one dose of study treatment.
|
Additional Information
Clinical Trial Transparency
Chiesi Farmaceutici S.p.A.
Phone: + 39 0521 2791
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Chiesi can publish and/or present any results of this study at scientific meetings, and to submit the clinical trial data to national and international Regulatory Authorities. Chiesi reserves the right to use such data for industrial purposes. Investigators will inform Chiesi before using the results of the study for publication or presentation, and agree to provide the Sponsor with a copy of the proposed presentation. Data from individual study sites must not be published separately.
- Publication restrictions are in place
Restriction type: OTHER