PT003 MDI Cardiovascular Safety Study

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)

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: PT005 MDI; Drug: PT001 MDI; Drug: PT003 MDI; Drug: Formoterol Fumarate 12 μg (Foradil® Aerolizer®)

• Study Type: Interventional
• Enrollment (Actual): 237
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Glebe, New South Wales, Australia
      • Pearl Investigative Site
  • Queensland
    • Caboolture, Queensland, Australia
      • Pearl Investigative Site
  • South Australia
    • Dawpark, South Australia, Australia
      • Pearl Investigative Site
    • Toorak Gardens, South Australia, Australia
      • Pearl Investigative Site
  • Victoria
    • Heidelberg, Victoria, Australia
      • Pearl Investigative Site
  • Western Australia
    • Nedlands, Western Australia, Australia
      • Pearl Investigative Site
• New Zealand
  • Dunedin
    • Caversham, Dunedin, New Zealand
      • Pearl Investigative Site
  • Hamilton
    • Private Bag, Hamilton, New Zealand
      • Pearl Investigative Site
  • North Island
    • Tauranga, North Island, New Zealand
      • Pearl Investigative Site
  • Wellington
    • Newtown, Wellington, New Zealand
      • Pearl Investigative Site
• United States
  • Arizona
    • Glendale, Arizona, United States
      • Pearl Investigative Site
  • California
    • Fullerton, California, United States
      • Pearl Investigative Site
    • Los Angeles, California, United States
      • Pearl Investigative Site
    • San Diego, California, United States
      • Pearl Investigative Site
  • Florida
    • Pensacola, Florida, United States
      • Pearl Investigative Site
  • Louisiana
    • Lafayette, Louisiana, United States
      • Pearl Investigative Site
  • Massachusetts
    • North Dartmouth, Massachusetts, United States
      • Pearl Investigative Site
  • Michigan
    • Livonia, Michigan, United States
      • Pearl Investigative Site
  • Oregon
    • Medford, Oregon, United States
      • Pearl Investigative Site
  • Texas
    • San Antonio, Texas, United States
      • Pearl Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Pearl Therapeutics, Inc.
• Investigators: Study Director: Colin Reisner, M.D., Pearl Therapeutics

Publications and helpful links

General Publications

• Ferguson GT, Reisner C, Pearle J, DePetrillo P, Maes A, Martin UJ. Cardiovascular safety profile of a fixed-dose combination of glycopyrrolate and formoterol fumarate delivered via metered dose inhaler using co-suspension delivery technology. Pulm Pharmacol Ther. 2018 Apr;49:67-74. doi: 10.1016/j.pupt.2018.01.007. Epub 2018 Feb 4.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): November 1, 2011
• Study Completion (Actual): November 1, 2011

Study Registration Dates

• First Submitted: May 5, 2011
• First Submitted That Met QC Criteria: May 6, 2011
• First Posted (Estimate): May 9, 2011

Study Record Updates

• Last Update Posted (Estimate): January 31, 2017
• Last Update Submitted That Met QC Criteria: December 7, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: COPD
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Formoterol Fumarate
• Other Study ID Numbers: PT003003