PT003 MDI Cardiovascular Safety Study

Phase 2

Completed

Conditions: Chronic Obstructive Pulmonary Disease

Interventions: Drug: PT005 MDI
Drug: Formoterol Fumarate 12 μg (Foradil® Aerolizer®)
Drug: PT003 MDI
Drug: PT001 MDI

Registration Number: NCT01349803

Lead Sponsor: Pearl Therapeutics, Inc.

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 237

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PT005 MDI	PT005 MDI	PT005 MDI
Formoterol Fumarate 12 μg (Foradil® Aerolizer®)	Formoterol Fumarate 12 μg (Foradil® Aerolizer®)	Formoterol Fumarate 12 μg (Foradil® Aerolizer®)
PT003 MDI	PT003 MDI	PT003 MDI
PT001 MDI	PT001 MDI	PT001 MDI

Primary Outcome Measures

Name	Time	Method
Change From Baseline in 24-Hour Mean Heart Rate Post-dose	14 days	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).

Secondary Outcome Measures

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