PT003 MDI Cardiovascular Safety Study

Study Overview
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Brief Summary
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This study is primarily a safety study. The primary and secondary endpoints are based on 24-hour Holter monitor assessments obtained on Day 14 relative to baseline.

Official Title
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A Randomized, Double-blind, Parallel Group, 14-day, Multi-Center Study to Evaluate the Safety of PT003, PT005, PT001 and Foradil® Aerolizer® (12 µg, Open Label) as Evaluated by Holter Monitoring, in Patients With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: PT005 MDI
* Drug: PT001 MDI
* Drug: PT003 MDI
* Drug: Formoterol Fumarate 12 μg (Foradil® Aerolizer®)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Signed written informed consent 40 - 80 years of age Clinical history of COPD with airflow limitation that is not fully reversible Females of non-child bearing potential or females of child bearing potential with negative pregnancy test; and acceptable contraceptive methods Current/former smokers with at least a 10 pack-year history of cigarette smoking A measured post- bronchodilator FEV1/FVC ratio of < or = 0.70 A measured post- bronchodilator FEV1 > or = 750ml or 30% predicted and < or = 80% of predicted normal values Able to change COPD treatment as required by protocol Acceptable baseline (Visit 2) Holter monitor recording Key Exclusion Criteria: Women who are pregnant or lactating Primary diagnosis of asthma Alpha-1 antitrypsin deficiency as the cause of COPD Active pulmonary diseases Prior lung volume reduction surgery Abnormal chest X-ray (or CT scan) not due to the presence of COPD Hospitalized due to poorly controlled COPD within 3 months of Screening Clinically significant medical conditions that preclude participation in the study (e.g. clinically significant abnormal ECG, uncontrolled hypertension, glaucoma, symptomatic prostatic hypertrophy) Cancer that has not been in complete remission for at least 5 years Treatment with investigational study drug or participation in another clinical trial or study within the last 30 days or 5 half lives Clinically significant abnormal findings during the baseline Holter recording Patients with a pacemaker or ICD/CRT/CRT_D devices Other inclusion/exclusion criteria as defined by the protocol

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PT005 MDI<br>PT005 MDI | Drug: PT005 MDI<br>* PT005 MDI administered as two puffs BID for 14 days<br>|
| Experimental: PT001 MDI<br>PT001 MDI | Drug: PT001 MDI<br>* PT001 MDI administered as two puffs BID for 14 days<br>|
| Experimental: PT003 MDI<br>PT003 MDI | Drug: PT003 MDI<br>* PT003 MDI administered as two puffs BID for 14 days<br>|
| Active Comparator: Formoterol Fumarate 12 μg (Foradil® Aerolizer®)<br>Formoterol Fumarate 12 μg (Foradil® Aerolizer®) | Drug: Formoterol Fumarate 12 μg (Foradil® Aerolizer®)<br>* Formoterol Fumarate 12 μg (Foradil® Aerolizer®) administered BID for 14 days<br>* Other names: Foradil® Aerolizer®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 24-Hour Mean Heart Rate Post-dose | 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). | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean FEV1 Trough | Trough FEV1 averaged over Day 7 and Day 14 | Day 7 to Day 14 | 
| Change From Baseline in 24-Hour Mean Heart Rate for Day 1 of Treatment | 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). | 24 hours | 
| Change From Baseline in Daytime Mean Heart Rate | 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). | Baseline, Day 1, and Day 14 | 
| Change From Baseline in Night Time Mean Heart Rate | 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). | Baseline, Day 1, and Day 14 | 
| Change From Baseline in 24-Hour Maximum Heart Rate | 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). | Baseline, Day 1, and Day 14 | 
| Change From Baseline in 24-Hour Minimum Heart Rate | 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). | Baseline, Day 1, and Day 14 | 
| Change From Baseline in Number of Isolated Ventricular Events Recorded During 24-Hour Holter Monitoring | 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). | Baseline, Day 1, and Day 14 | 
| Change From Baseline in the Number of Ventricular Couplets Recorded During 24-Hour Holter Monitoring | 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). | Baseline, Day 1, and Day 14 | 
| Change From Baseline in the Number of Ventricular Runs Recorded During 24-Hour Holter Monitoring | 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). | Baseline, Day 1, and Day 14 | 
| Change From Baseline in the Number of Isolated Supraventricular Events Recorded During 24-Hour Holter Monitoring | 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). | Baseline, Day 1, and Day 14 | 
| Change From Baseline in the Number of Supraventricular Couplets Recorded During 24-Hour Holter Monitoring | 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). | Baseline, Day 1, and Day 14 | 
| Change From Baseline in the Number of Supraventricular Runs Recorded During 24-Hour Holter Monitoring | 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). | Baseline, Day 1, and Day 14 | 
| Change From Baseline in the Number of Bradycardia Episodes Recorded During 24-Hour Holter Monitoring | 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). | Baseline, Day 1, and Day 14 | 
| Change From Baseline in the Number of Tachycardia Episodes Recorded During 24-Hour Holter Monitoring | 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). | Baseline, Day 1, and Day 14 | 
| Mean Change From Baseline in QTcF Interval | 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). | Baseline, Day 1, Day 7, and Day 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD