Clinical trial NCT01349803: PT003 MDI Cardiovascular Safety Study
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Keywords: COPD
Lead sponsor: Pearl Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2011-05-09
Enrollment: 237
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in 24-Hour Mean Heart Rate Post-dose
timeFrame: 14 days
Secondary outcomes:
measure: Change From Baseline in Mean FEV1 Trough
timeFrame: Day 7 to Day 14
measure: Change From Baseline in 24-Hour Mean Heart Rate for Day 1 of Treatment
timeFrame: 24 hours
measure: Change From Baseline in Daytime Mean Heart Rate
timeFrame: Baseline, Day 1, and Day 14
measure: Change From Baseline in Night Time Mean Heart Rate
timeFrame: Baseline, Day 1, and Day 14
measure: Change From Baseline in 24-Hour Maximum Heart Rate
timeFrame: Baseline, Day 1, and Day 14
measure: Change From Baseline in 24-Hour Minimum Heart Rate
timeFrame: Baseline, Day 1, and Day 14
measure: Change From Baseline in Number of Isolated Ventricular Events Recorded During 24-Hour Holter Monitoring
timeFrame: Baseline, Day 1, and Day 14
measure: Change From Baseline in the Number of Ventricular Couplets Recorded During 24-Hour Holter Monitoring
timeFrame: Baseline, Day 1, and Day 14
measure: Change From Baseline in the Number of Ventricular Runs Recorded During 24-Hour Holter Monitoring
timeFrame: Baseline, Day 1, and Day 14
measure: Change From Baseline in the Number of Isolated Supraventricular Events Recorded During 24-Hour Holter Monitoring
timeFrame: Baseline, Day 1, and Day 14
measure: Change From Baseline in the Number of Supraventricular Couplets Recorded During 24-Hour Holter Monitoring
timeFrame: Baseline, Day 1, and Day 14
measure: Change From Baseline in the Number of Supraventricular Runs Recorded During 24-Hour Holter Monitoring
timeFrame: Baseline, Day 1, and Day 14
measure: Change From Baseline in the Number of Bradycardia Episodes Recorded During 24-Hour Holter Monitoring
timeFrame: Baseline, Day 1, and Day 14
measure: Change From Baseline in the Number of Tachycardia Episodes Recorded During 24-Hour Holter Monitoring
timeFrame: Baseline, Day 1, and Day 14
measure: Mean Change From Baseline in QTcF Interval
timeFrame: Baseline, Day 1, Day 7, and Day 14
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Pearl Investigative Site
state: Arizona
city: Fullerton
country: United States
facility: Pearl Investigative Site
state: California
city: Los Angeles
country: United States
facility: Pearl Investigative Site
state: California
city: San Diego
country: United States
facility: Pearl Investigative Site
state: California
city: Pensacola
country: United States
facility: Pearl Investigative Site
state: Florida
city: Lafayette
country: United States
facility: Pearl Investigative Site
state: Louisiana
city: North Dartmouth
country: United States
facility: Pearl Investigative Site
state: Massachusetts
city: Livonia
country: United States
facility: Pearl Investigative Site
state: Michigan
city: Medford
country: United States
facility: Pearl Investigative Site
state: Oregon
city: San Antonio
country: United States
facility: Pearl Investigative Site
state: Texas
city: Glebe
country: Australia
facility: Pearl Investigative Site
state: New South Wales
city: Caboolture
country: Australia
facility: Pearl Investigative Site
state: Queensland
city: Dawpark
country: Australia
facility: Pearl Investigative Site
state: South Australia
city: Toorak Gardens
country: Australia
facility: Pearl Investigative Site
state: South Australia
city: Heidelberg
country: Australia
facility: Pearl Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Pearl Investigative Site
state: Western Australia
city: Caversham
country: New Zealand
facility: Pearl Investigative Site
state: Dunedin
city: Private Bag
country: New Zealand
facility: Pearl Investigative Site
state: Hamilton
city: Tauranga
country: New Zealand
facility: Pearl Investigative Site
state: North Island
city: Newtown
country: New Zealand
facility: Pearl Investigative Site
state: Wellington
Study officials:
affiliation: Pearl Therapeutics
name: Colin Reisner, M.D.
role: STUDY_DIRECTOR
References:
citation: 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.