Trial Outcomes & Findings for PT003 MDI Cardiovascular Safety Study (NCT NCT01349803)
NCT ID: NCT01349803
Last Updated: 2017-01-31
Results Overview
The primary safety objective of this study was to compare the change in mean heart rate averaged over 24 hours post-dose, following twice daily dosing over 14 days with PT003 MDI, PT005 MDI, PT001 MDI or Foradil Aerolizer compared to baseline in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
COMPLETED
PHASE2
237 participants
14 days
2017-01-31
Participant Flow
Conducted at 15 sites throughout the US, Australia, and New Zealand from May 2011 - November 2011. Study participation was a maximum of 7 weeks.
Study was a multicenter, randomized, double-blind, parallel group, chronic dosing (14 days) study; each patient was randomized to receive 1 of 4 possible treatments over the course of a 14-day treatment period
Participant milestones
| Measure |
FF MDI (PT005)
FF MDI 9.6 mcg
|
GP MDI (PT001)
GP MDI 36 mcg
|
GFF MDI (PT003)
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
60
|
58
|
60
|
59
|
|
Overall Study
COMPLETED
|
59
|
57
|
57
|
57
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
3
|
2
|
Reasons for withdrawal
| Measure |
FF MDI (PT005)
FF MDI 9.6 mcg
|
GP MDI (PT001)
GP MDI 36 mcg
|
GFF MDI (PT003)
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
0
|
0
|
2
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
|
Overall Study
Protocol-specified criteria
|
0
|
1
|
3
|
0
|
Baseline Characteristics
PT003 MDI Cardiovascular Safety Study
Baseline characteristics by cohort
| Measure |
FF MDI (PT005)
n=60 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=60 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=59 Participants
Formoterol Fumarate 12 μg
|
Total
n=237 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
64.1 Years
STANDARD_DEVIATION 8.13 • n=5 Participants
|
63.3 Years
STANDARD_DEVIATION 7.93 • n=7 Participants
|
64.3 Years
STANDARD_DEVIATION 7.38 • n=5 Participants
|
64.1 Years
STANDARD_DEVIATION 7.91 • n=4 Participants
|
64.0 Years
STANDARD_DEVIATION 7.80 • n=21 Participants
|
|
Gender
Female
|
33 Participants
n=5 Participants
|
32 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
31 Participants
n=4 Participants
|
122 Participants
n=21 Participants
|
|
Gender
Male
|
27 Participants
n=5 Participants
|
26 Participants
n=7 Participants
|
34 Participants
n=5 Participants
|
28 Participants
n=4 Participants
|
115 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 14 daysPopulation: Safety Holter Monitoring Population: a sub-set of the safety population that had at least 18 hours of Holter monitoring data at Screening and at Day 1 and/or Day 14. Exclusions from this population were identified prior to database lock and unblinding.
The primary safety objective of this study was to compare the change in mean heart rate averaged over 24 hours post-dose, following twice daily dosing over 14 days with PT003 MDI, PT005 MDI, PT001 MDI or Foradil Aerolizer compared to baseline in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
Outcome measures
| Measure |
FF MDI (PT005)
n=59 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=57 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=55 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=55 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in 24-Hour Mean Heart Rate Post-dose
|
-0.19 bpm
Interval -1.38 to 1.0
|
-1.84 bpm
Interval -3.05 to -0.63
|
0.40 bpm
Interval -0.84 to 1.63
|
-0.09 bpm
Interval -1.32 to 1.15
|
SECONDARY outcome
Timeframe: Day 7 to Day 14Population: MITT - patients from the ITT population who completed at least one evaluable FEV1 spirometry assessment for baseline (pre-dose on Day 1) and had an evaluable FEV1 spirometry assessment on at least one of the following: Day 7 pre-dose or Day 14 pre-dose (or both).
Trough FEV1 averaged over Day 7 and Day 14
Outcome measures
| Measure |
FF MDI (PT005)
n=57 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=49 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=53 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=55 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in Mean FEV1 Trough
|
0.091 Liters
Interval 0.049 to 0.134
|
0.126 Liters
Interval 0.08 to 0.172
|
0.251 Liters
Interval 0.207 to 0.295
|
0.124 Liters
Interval 0.081 to 0.167
|
SECONDARY outcome
Timeframe: 24 hoursPopulation: Safety Holter Monitoring Population: a sub-set of the safety population that had at least 18 hours of Holter monitoring data at Screening and at Day 1 and/or Day 14. Exclusions from this population were identified prior to database lock and unblinding.
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation).
Outcome measures
| Measure |
FF MDI (PT005)
n=60 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=57 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=57 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in 24-Hour Mean Heart Rate for Day 1 of Treatment
|
0.56 bpm
Interval -0.73 to 1.85
|
-0.44 bpm
Interval -1.75 to 0.87
|
0.92 bpm
Interval -0.4 to 2.24
|
0.31 bpm
Interval -1.01 to 1.63
|
SECONDARY outcome
Timeframe: Baseline, Day 1, and Day 14Population: Safety Holter Monitoring Population: a sub-set of the safety population that had at least 18 hours of Holter monitoring data at Screening and at Day 1 and/or Day 14. Exclusions from this population were identified prior to database lock and unblinding.
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation).
Outcome measures
| Measure |
FF MDI (PT005)
n=59 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=57 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=57 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in Daytime Mean Heart Rate
Day 1
|
0.00 bpm
Interval -1.4 to 1.4
|
-0.52 bpm
Interval -1.93 to 0.9
|
0.16 bpm
Interval -1.27 to 1.58
|
-0.17 bpm
Interval -1.6 to 1.25
|
|
Change From Baseline in Daytime Mean Heart Rate
Day 14
|
-1.22 bpm
Interval -2.64 to 0.2
|
-2.00 bpm
Interval -3.45 to -0.56
|
-0.40 bpm
Interval -1.87 to 1.07
|
-0.54 bpm
Interval -2.01 to 0.93
|
SECONDARY outcome
Timeframe: Baseline, Day 1, and Day 14Population: Safety Holter Monitoring Population: a sub-set of the safety population that had at least 18 hours of Holter monitoring data at Screening and at Day 1 and/or Day 14. Exclusions from this population were identified prior to database lock and unblinding.
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation).
Outcome measures
| Measure |
FF MDI (PT005)
n=59 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=57 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=55 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=57 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in Night Time Mean Heart Rate
Day 14
|
0.04 bpm
Interval -1.94 to 2.03
|
-0.88 bpm
Interval -2.89 to 1.12
|
0.11 bpm
Interval -1.93 to 2.15
|
1.05 bpm
Interval -0.99 to 3.09
|
|
Change From Baseline in Night Time Mean Heart Rate
Day 1
|
3.05 bpm
Interval 1.63 to 4.47
|
-0.54 bpm
Interval -1.99 to 0.9
|
2.95 bpm
Interval 1.48 to 4.42
|
0.70 bpm
Interval -0.74 to 2.15
|
SECONDARY outcome
Timeframe: Baseline, Day 1, and Day 14Population: Safety Holter Monitoring Population: a sub-set of the safety population that had at least 18 hours of Holter monitoring data at Screening and at Day 1 and/or Day 14. Exclusions from this population were identified prior to database lock and unblinding.
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation).
Outcome measures
| Measure |
FF MDI (PT005)
n=60 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=57 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=57 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in 24-Hour Maximum Heart Rate
Day 1
|
-4.71 bpm
Interval -8.72 to -0.69
|
-1.88 bpm
Interval -5.96 to 2.2
|
-1.91 bpm
Interval -6.03 to 2.21
|
0.31 bpm
Interval -3.81 to 4.42
|
|
Change From Baseline in 24-Hour Maximum Heart Rate
Day 14
|
0.75 bpm
Interval -3.46 to 4.97
|
-2.21 bpm
Interval -6.5 to 2.07
|
-0.06 bpm
Interval -4.42 to 4.31
|
-1.13 bpm
Interval -5.49 to 3.23
|
SECONDARY outcome
Timeframe: Baseline, Day 1, and Day 14Population: Safety Holter Monitoring Population: a sub-set of the safety population that had at least 18 hours of Holter monitoring data at Screening and at Day 1 and/or Day 14. Exclusions from this population were identified prior to database lock and unblinding.
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation).
Outcome measures
| Measure |
FF MDI (PT005)
n=60 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=57 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=57 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in 24-Hour Minimum Heart Rate
Day 1
|
0.05 bpm
Interval -1.19 to 1.29
|
-0.03 bpm
Interval -1.3 to 1.23
|
0.50 bpm
Interval -0.78 to 1.78
|
0.45 bpm
Interval -0.82 to 1.72
|
|
Change From Baseline in 24-Hour Minimum Heart Rate
Day 14
|
-0.79 bpm
Interval -1.92 to 0.35
|
-1.92 bpm
Interval -3.07 to -0.77
|
-0.21 bpm
Interval -1.38 to 0.97
|
0.88 bpm
Interval -0.3 to 2.05
|
SECONDARY outcome
Timeframe: Baseline, Day 1, and Day 14Population: Safety Holter Monitoring Population: a sub-set of the safety population that had at least 18 hours of Holter monitoring data at Screening and at Day 1 and/or Day 14. Exclusions from this population were identified prior to database lock and unblinding.
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation).
Outcome measures
| Measure |
FF MDI (PT005)
n=60 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=57 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=57 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in Number of Isolated Ventricular Events Recorded During 24-Hour Holter Monitoring
Day 1
|
1.31 Ventricular events / hour
Standard Error 1.605 • Interval -0.25 to 0.24
|
0.56 Ventricular events / hour
Standard Error 0.853 • Interval -0.32 to 0.18
|
1.59 Ventricular events / hour
Standard Error 1.879 • Interval -0.19 to 0.31
|
0.45 Ventricular events / hour
Standard Error 0.580 • Interval -0.24 to 0.26
|
|
Change From Baseline in Number of Isolated Ventricular Events Recorded During 24-Hour Holter Monitoring
Day 14
|
3.09 Ventricular events / hour
Standard Error 4.092 • Interval -0.31 to 0.16
|
0.62 Ventricular events / hour
Standard Error 1.088 • Interval -0.5 to -0.03
|
-0.10 Ventricular events / hour
Standard Error 0.541 • Interval -0.17 to 0.31
|
-0.54 Ventricular events / hour
Standard Error 0.424 • Interval 0.04 to 0.52
|
SECONDARY outcome
Timeframe: Baseline, Day 1, and Day 14Population: Safety Holter Monitoring Population: a sub-set of the safety population that had at least 18 hours of Holter monitoring data at Screening and at Day 1 and/or Day 14. Exclusions from this population were identified prior to database lock and unblinding.
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation).
Outcome measures
| Measure |
FF MDI (PT005)
n=60 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=57 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=57 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in the Number of Ventricular Couplets Recorded During 24-Hour Holter Monitoring
Day 1
|
0.09 Ventricular couplets / hour
Standard Error 0.071 • Interval -0.25 to 0.24
|
0.00 Ventricular couplets / hour
Standard Error 0.005 • Interval -0.32 to 0.18
|
0.00 Ventricular couplets / hour
Standard Error 0.009 • Interval -0.19 to 0.31
|
0.00 Ventricular couplets / hour
Standard Error 0.005 • Interval -0.24 to 0.26
|
|
Change From Baseline in the Number of Ventricular Couplets Recorded During 24-Hour Holter Monitoring
Day 14
|
0.02 Ventricular couplets / hour
Standard Error 0.021 • Interval -0.31 to 0.16
|
0.00 Ventricular couplets / hour
Standard Error 0.009 • Interval -0.5 to -0.03
|
-0.03 Ventricular couplets / hour
Standard Error 0.033 • Interval -0.17 to 0.31
|
-0.01 Ventricular couplets / hour
Standard Error 0.004 • Interval 0.04 to 0.52
|
SECONDARY outcome
Timeframe: Baseline, Day 1, and Day 14Population: Safety Holter Monitoring Population: a sub-set of the safety population that had at least 18 hours of Holter monitoring data at Screening and at Day 1 and/or Day 14. Exclusions from this population were identified prior to database lock and unblinding.
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation).
Outcome measures
| Measure |
FF MDI (PT005)
n=60 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=57 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=57 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in the Number of Ventricular Runs Recorded During 24-Hour Holter Monitoring
Day 14
|
-0.004 Ventricular runs / hour
Standard Error 0.0021 • Interval -0.31 to 0.16
|
0.001 Ventricular runs / hour
Standard Error 0.0029 • Interval -0.5 to -0.03
|
0.001 Ventricular runs / hour
Standard Error 0.0013 • Interval -0.17 to 0.31
|
-0.004 Ventricular runs / hour
Standard Error 0.0037 • Interval 0.04 to 0.52
|
|
Change From Baseline in the Number of Ventricular Runs Recorded During 24-Hour Holter Monitoring
Day 1
|
-0.003 Ventricular runs / hour
Standard Error 0.0024 • Interval -0.25 to 0.24
|
-0.001 Ventricular runs / hour
Standard Error 0.0017 • Interval -0.32 to 0.18
|
0.001 Ventricular runs / hour
Standard Error 0.0019 • Interval -0.19 to 0.31
|
-0.003 Ventricular runs / hour
Standard Error 0.0040 • Interval -0.24 to 0.26
|
SECONDARY outcome
Timeframe: Baseline, Day 1, and Day 14Population: Safety Holter Monitoring Population: a sub-set of the safety population that had at least 18 hours of Holter monitoring data at Screening and at Day 1 and/or Day 14. Exclusions from this population were identified prior to database lock and unblinding.
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation).
Outcome measures
| Measure |
FF MDI (PT005)
n=60 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=57 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=57 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in the Number of Isolated Supraventricular Events Recorded During 24-Hour Holter Monitoring
Day 1
|
7.72 Supraventricular events / hour
Standard Error 6.971 • Interval -0.25 to 0.24
|
0.74 Supraventricular events / hour
Standard Error 0.804 • Interval -0.32 to 0.18
|
-4.55 Supraventricular events / hour
Standard Error 5.947 • Interval -0.19 to 0.31
|
15.36 Supraventricular events / hour
Standard Error 16.359 • Interval -0.24 to 0.26
|
|
Change From Baseline in the Number of Isolated Supraventricular Events Recorded During 24-Hour Holter Monitoring
Day 14
|
3.61 Supraventricular events / hour
Standard Error 5.179 • Interval -0.31 to 0.16
|
-9.29 Supraventricular events / hour
Standard Error 9.398 • Interval -0.5 to -0.03
|
3.61 Supraventricular events / hour
Standard Error 5.179 • Interval -0.17 to 0.31
|
5.81 Supraventricular events / hour
Standard Error 11.320 • Interval 0.04 to 0.52
|
SECONDARY outcome
Timeframe: Baseline, Day 1, and Day 14Population: Safety Holter Monitoring Population: a sub-set of the safety population that had at least 18 hours of Holter monitoring data at Screening and at Day 1 and/or Day 14. Exclusions from this population were identified prior to database lock and unblinding.
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation).
Outcome measures
| Measure |
FF MDI (PT005)
n=60 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=57 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=57 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in the Number of Supraventricular Couplets Recorded During 24-Hour Holter Monitoring
Day 1
|
0.03 Supraventricular couplets / hour
Standard Error 0.034 • Interval -0.25 to 0.24
|
0.01 Supraventricular couplets / hour
Standard Error 0.021 • Interval -0.32 to 0.18
|
0.05 Supraventricular couplets / hour
Standard Error 0.019 • Interval -0.19 to 0.31
|
0.04 Supraventricular couplets / hour
Standard Error 0.065 • Interval -0.24 to 0.26
|
|
Change From Baseline in the Number of Supraventricular Couplets Recorded During 24-Hour Holter Monitoring
Day 14
|
0.01 Supraventricular couplets / hour
Standard Error 0.025 • Interval -0.31 to 0.16
|
0.00 Supraventricular couplets / hour
Standard Error 0.017 • Interval -0.5 to -0.03
|
0.00 Supraventricular couplets / hour
Standard Error 0.018 • Interval -0.17 to 0.31
|
-0.02 Supraventricular couplets / hour
Standard Error 0.020 • Interval 0.04 to 0.52
|
SECONDARY outcome
Timeframe: Baseline, Day 1, and Day 14Population: Safety Holter Monitoring Population: a sub-set of the safety population that had at least 18 hours of Holter monitoring data at Screening and at Day 1 and/or Day 14. Exclusions from this population were identified prior to database lock and unblinding.
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation).
Outcome measures
| Measure |
FF MDI (PT005)
n=60 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=57 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=57 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in the Number of Supraventricular Runs Recorded During 24-Hour Holter Monitoring
Day 1
|
0.00 Supraventricular runs / hour
Standard Error 0.014 • Interval -0.25 to 0.24
|
0.02 Supraventricular runs / hour
Standard Error 0.011 • Interval -0.32 to 0.18
|
0.01 Supraventricular runs / hour
Standard Error 0.011 • Interval -0.19 to 0.31
|
0.01 Supraventricular runs / hour
Standard Error 0.010 • Interval -0.24 to 0.26
|
|
Change From Baseline in the Number of Supraventricular Runs Recorded During 24-Hour Holter Monitoring
Day 14
|
0.01 Supraventricular runs / hour
Standard Error 0.013 • Interval -0.31 to 0.16
|
0.02 Supraventricular runs / hour
Standard Error 0.015 • Interval -0.5 to -0.03
|
0.00 Supraventricular runs / hour
Standard Error 0.012 • Interval -0.17 to 0.31
|
0.01 Supraventricular runs / hour
Standard Error 0.014 • Interval 0.04 to 0.52
|
SECONDARY outcome
Timeframe: Baseline, Day 1, and Day 14Population: Safety Holter Monitoring Population: a sub-set of the safety population that had at least 18 hours of Holter monitoring data at Screening and at Day 1 and/or Day 14. Exclusions from this population were identified prior to database lock and unblinding.
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation).
Outcome measures
| Measure |
FF MDI (PT005)
n=60 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=57 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=57 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in the Number of Bradycardia Episodes Recorded During 24-Hour Holter Monitoring
Day 1
|
-0.04 Bradycardia episodes / hour
Standard Error 0.139 • Interval -0.25 to 0.24
|
-0.02 Bradycardia episodes / hour
Standard Error 0.083 • Interval -0.32 to 0.18
|
0.11 Bradycardia episodes / hour
Standard Error 0.193 • Interval -0.19 to 0.31
|
0.03 Bradycardia episodes / hour
Standard Error 0.036 • Interval -0.24 to 0.26
|
|
Change From Baseline in the Number of Bradycardia Episodes Recorded During 24-Hour Holter Monitoring
Day 14
|
-0.02 Bradycardia episodes / hour
Standard Error 0.111 • Interval -0.31 to 0.16
|
0.40 Bradycardia episodes / hour
Standard Error 0.210 • Interval -0.5 to -0.03
|
0.27 Bradycardia episodes / hour
Standard Error 0.283 • Interval -0.17 to 0.31
|
0.13 Bradycardia episodes / hour
Standard Error 0.132 • Interval 0.04 to 0.52
|
SECONDARY outcome
Timeframe: Baseline, Day 1, and Day 14Population: Safety Holter Monitoring Population: a sub-set of the safety population that had at least 18 hours of Holter monitoring data at Screening and at Day 1 and/or Day 14. Exclusions from this population were identified prior to database lock and unblinding.
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation).
Outcome measures
| Measure |
FF MDI (PT005)
n=60 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=57 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=57 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Change From Baseline in the Number of Tachycardia Episodes Recorded During 24-Hour Holter Monitoring
Day 1
|
-0.16 Tachycardia episodes / hour
Standard Error 0.170 • Interval -0.25 to 0.24
|
-0.24 Tachycardia episodes / hour
Standard Error 0.209 • Interval -0.32 to 0.18
|
-0.02 Tachycardia episodes / hour
Standard Error 0.160 • Interval -0.19 to 0.31
|
-0.09 Tachycardia episodes / hour
Standard Error 0.197 • Interval -0.24 to 0.26
|
|
Change From Baseline in the Number of Tachycardia Episodes Recorded During 24-Hour Holter Monitoring
Day 14
|
-0.23 Tachycardia episodes / hour
Standard Error 0.146 • Interval -0.31 to 0.16
|
-0.34 Tachycardia episodes / hour
Standard Error 0.229 • Interval -0.5 to -0.03
|
0.22 Tachycardia episodes / hour
Standard Error 0.154 • Interval -0.17 to 0.31
|
-0.01 Tachycardia episodes / hour
Standard Error 0.206 • Interval 0.04 to 0.52
|
SECONDARY outcome
Timeframe: Baseline, Day 1, Day 7, and Day 14Population: Safety Population
The secondary objectives of the study was to further characterize cardiovascular safety parameters of all treatment groups including the maximum 24-hour heart rate, mean night-time and day-time heart rate, ventricular ectopic events, ventricular couplets, ventricular runs, the number of supraventricular runs, and sustained ventricular tachycardia (VT), supraventricular ectopic events, and other clinically relevant arrhythmias (such as atrial fibrillation).
Outcome measures
| Measure |
FF MDI (PT005)
n=60 Participants
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 Participants
GP MDI 36 mcg
|
GFF MDI (PT003)
n=60 Participants
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=59 Participants
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Mean Change From Baseline in QTcF Interval
Day 1: Post-dose 30 minutes
|
1.53 msec
Standard Deviation 11.238 • Interval -0.25 to 0.24
|
4.67 msec
Standard Deviation 12.548 • Interval -0.32 to 0.18
|
3.27 msec
Standard Deviation 9.223 • Interval -0.19 to 0.31
|
3.71 msec
Standard Deviation 9.816 • Interval -0.24 to 0.26
|
|
Mean Change From Baseline in QTcF Interval
Day 1: Post-dose 2 hours
|
1.75 msec
Standard Deviation 13.861 • Interval -0.31 to 0.16
|
3.57 msec
Standard Deviation 12.866 • Interval -0.5 to -0.03
|
1.62 msec
Standard Deviation 13.785 • Interval -0.17 to 0.31
|
5.25 msec
Standard Deviation 11.709 • Interval 0.04 to 0.52
|
|
Mean Change From Baseline in QTcF Interval
Day 1: Post-dose 24 hours
|
-0.09 msec
Standard Deviation 13.309
|
1.23 msec
Standard Deviation 16.142
|
-1.43 msec
Standard Deviation 12.724
|
0.36 msec
Standard Deviation 10.989
|
|
Mean Change From Baseline in QTcF Interval
Day 7: Pre-dose
|
-1.80 msec
Standard Deviation 10.362
|
1.40 msec
Standard Deviation 14.713
|
1.06 msec
Standard Deviation 12.151
|
3.85 msec
Standard Deviation 12.599
|
|
Mean Change From Baseline in QTcF Interval
Day 14: Pre-dose
|
-0.59 msec
Standard Deviation 12.523
|
1.79 msec
Standard Deviation 13.028
|
-0.42 msec
Standard Deviation 11.910
|
1.53 msec
Standard Deviation 14.085
|
|
Mean Change From Baseline in QTcF Interval
Day 14: Post-dose 30 minutes
|
1.21 msec
Standard Deviation 13.350
|
4.10 msec
Standard Deviation 17.202
|
2.23 msec
Standard Deviation 13.194
|
1.20 msec
Standard Deviation 14.458
|
|
Mean Change From Baseline in QTcF Interval
Day 14: Post-dose 2 hours
|
0.44 msec
Standard Deviation 12.521
|
6.02 msec
Standard Deviation 16.774
|
5.01 msec
Standard Deviation 14.861
|
3.98 msec
Standard Deviation 14.135
|
|
Mean Change From Baseline in QTcF Interval
Day 14: Post-dose 24 hours
|
-1.32 msec
Standard Deviation 12.738
|
-0.05 msec
Standard Deviation 13.794
|
-1.93 msec
Standard Deviation 11.269
|
1.44 msec
Standard Deviation 16.086
|
Adverse Events
FF MDI (PT005)
GP MDI (PT001)
GFF MDI (PT003)
Foradil® Aerolizer®
Serious adverse events
| Measure |
FF MDI (PT005)
n=60 participants at risk
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 participants at risk
GP MDI 36 mcg
|
GFF MDI (PT003)
n=60 participants at risk
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=59 participants at risk
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.7%
1/60 • Number of events 1 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
0.00%
0/58 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
1.7%
1/60 • Number of events 1 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
1.7%
1/59 • Number of events 1 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
Other adverse events
| Measure |
FF MDI (PT005)
n=60 participants at risk
FF MDI 9.6 mcg
|
GP MDI (PT001)
n=58 participants at risk
GP MDI 36 mcg
|
GFF MDI (PT003)
n=60 participants at risk
GFF MDI 36/9.6 mcg
|
Foradil® Aerolizer®
n=59 participants at risk
Formoterol Fumarate 12 μg
|
|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.3%
2/60 • Number of events 2 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
5.2%
3/58 • Number of events 3 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
0.00%
0/60 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
1.7%
1/59 • Number of events 1 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/60 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
1.7%
1/58 • Number of events 1 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
1.7%
1/60 • Number of events 1 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
5.1%
3/59 • Number of events 3 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
|
Nervous system disorders
Tremor
|
6.7%
4/60 • Number of events 5 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
0.00%
0/58 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
1.7%
1/60 • Number of events 1 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
1.7%
1/59 • Number of events 1 • Adverse events (AEs) and Serious Adverse Events (SAEs) were collected from the time the subject signs the informed consent form up to 14 days following the last dose of study drug.
All patients who were randomized to a treatment, received at least one dose of the study treatment, and had any safety data after starting study treatment. A patient who used a study treatment, but took less than one full dose qualified for this population.
|
Additional Information
Colin Reisner, MD, FCCP, FAAAAI
Pearl Therapeutics, Inc
Results disclosure agreements
- Principal investigator is a sponsor employee Drafts of any and all publications or presentations of this study must be submitted at least 30 days prior to submission for publication or presentation to Pearl Therapeutics for review, approval, and to ensure consistency. Pearl Therapeutics has the right to request appropriate modification to correct facts and to represent its opinions, or the opinions of the publication committee, if these differ with the proposed publication.
- Publication restrictions are in place
Restriction type: OTHER