- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02685293
Study to Evaluate the Treatment Effect of PT003 on Cardiovascular Hemodynamics in Subjects With Moderate to Severe COPD
August 12, 2019 updated by: Pearl Therapeutics, Inc.
A Randomized, Phase IIIb, Two-period , Double-blind, Two-treatment, Chronic-dosing (7 Days), Single-center Crossover Study to Evaluate the Treatment Effect of PT003 on Cardiovascular Hemodynamics in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease, Compared With Placebo
This is a randomized, double-blind, placebo-controlled, single-center, chronic-dosing (7 days), two-period, two-treatment, cross-over study to evaluate the treatment effect of PT003 compared with that of Placebo MDI on Cardiovascular Hemodynamics following chronic-dosing (7 days) in subjects with moderate to severe COPD.
Study Overview
Study Type
Interventional
Enrollment (Actual)
4
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Alabama
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Birmingham, Alabama, United States, 35294
- Research Site
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
40 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- At least 40 years of age and no older than 80 at Visit 1.
- Women of non-child bearing potential,or negative serum pregnancy test at Screening, and agrees to acceptable contraceptive methods used consistently and correctly from Screening until 14 days after final visit
- Evidence of lung hyperinflation
- Subjects with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS)
- Current or former smokers with a history of at least 10 pack-years of cigarette smoking.
- Pre- and Post-bronchodilator FEV1/FVC ratio must be <0.70
- Post-bronchodilator FEV1 must be ≥30% to <65% predicted normal value, calculated using NHANES III reference equations.
Exclusion Criteria:
- Significant diseases or conditions other than COPD which, in the opinion of the Investigator, may put the patient at risk
- Women who are pregnant or lactating or are planning to become pregnant during the course of the study
- Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma or other active pulmonary disease
- Subjects who have been hospitalized due to poorly controlled COPD within 3 months prior to Screening
- Subjects who have poorly controlled COPD, defined as acute worsening of COPD that requires treatment with oral corticosteroids or antibiotics within 6 weeks prior to Screening or during the Screening Period
- Subjects who have clinically significant uncontrolled hypertension.
- Subjects with symptomatic prostatic hypertrophy that is clinically significant and not adequately controlled with appropriate therapy, in the opinion of the Investigator.
- Subjects with bladder neck obstruction or urinary retention that is clinically significant in the opinion of the Investigator.
- Subjects with a calculated creatinine clearance ≤30 mL/minute using Chronic Kidney Disease Epidemiology Collaboration. (CKD-EPI) formula at Screening and on repeat testing prior to Visit 2.
- Subjects with abnormal liver function tests defined as AST, ALT, or total bilirubin ≥ 1.5 times upper limit of normal at Screening and on repeat testing prior to Visit 2
- Subjects who have cancer that has not been in complete remission for at least five years.
- Subjects with a diagnosis of glaucoma, who in the opinion of the Investigator, have not been adequately treated.
- Subjects with a clinically significant ECG
- Subjects who were previously enrolled in any previous PT001, PT003, or PT005 study conducted or sponsored by Pearl.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: GFF MDI (PT003)
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI)
|
Glycopyrronium and Formoterol Fumarate Inhalation Aerosol; PT003, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (GFF MDI)
|
Placebo Comparator: Placebo MDI
Placebo Metered Dose Inhaler (MDI) for Glycopyrronium and Formoterol Fumarate Inhalation Aerosol
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Placebo Metered Dose Inhaler (MDI) for Glycopyrronium and Formoterol Fumarate Inhalation Aerosol
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Right Ventricular End Diastolic Volume Index (RVEDVi) at 2-3 Hours Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of right ventricular (RV) volume was performed using magnetic resonance imaging (MRI) using RV end diastolic volume (RVEDV), 2-3 hours after dosing on Day 8 of each treatment period.
RVEDV was normalized to body surface area (BSA) to provide the indexed counterpart (RVEDVi).
Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Aortic Left Ventricular Stroke Volume (LVSV) at 2-3 Hours Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of LVSV was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period.
Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Change From Baseline in Right Ventricular Stroke Volume (RVSV) at 2-3 Hours Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of RVSV, phase contrast from pulmonic valve, was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period.
Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Change From Baseline in Pulmonary Artery Velocity at 2-3 Hours Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of Pulmonary Artery Velocity was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period.
Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVi) at 2-3 Hours Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of left ventricular (LV) volume was performed using MRI using LV end diastolic volume (LVEDV), 2-3 hours after dosing of Day 8 of each treatment period.
LVEDV was normalized to BSA to provide the indexed counterpart (LVEDVi).
Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Change From Baseline in Cardiac Output at 2-3 Hours Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of cardiac output was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period.
Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Change From Baseline in Pulmonary Vascular Resistance (PVR) at 30 and 60 Minutes Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of PVR was performed by impedance cardiography at 30 and 60 minutes after dosing on Day 8 of each treatment period.
Baseline for was defined as the average of the subject values obtained pre-dose on Day 1 of each treatment period.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Change From Baseline in Pulmonary Artery/Aortic Diameter Ratio (PA:A) at 2-3 Hours Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of PA:A was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period.
Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Change From Baseline in Left Atrial End Diastolic Volume (LAEDV) at 2-3 Hours Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of LAEDV was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period.
Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Change From Baseline in Left Atrial End Systolic Volume (LAESV) at 2-3 Hours Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of LAESV was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period.
Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Change From Baseline in Left Atrial Ejection Fraction (LAEF) at 2-3 Hours Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of LAEF was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period.
Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVi) at 2-3 Hours Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of LV volume was performed using MRI using LV end systolic volume (LVESV), 2-3 hours after dosing on Day 8 of each treatment period.
LVESV was normalized to BSA to provide the indexed counterpart (LVESVi).
Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Change From Baseline in Right Ventricular End Systolic Volume Index (RVESVi) at 2-3 Hours Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of RV volume was performed using MRI using RV end systolic volume (RVESV), 2-3 hours after dosing on Day 8 of each treatment period.
RVESV was normalized to BSA to provide the indexed counterpart (RVESVi).
Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Change From Baseline in Pulsatility Index Aorta (PIAo) at 2-3 Hours Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of PIAo was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period.
Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Change From Baseline in Pulmonary Artery Pulsatility Index (PAPi) at 2-3 Hours Post-dose on Day 8
Time Frame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Assessment of PAPi was performed using MRI, 2-3 hours after dosing on Day 8 of each treatment period.
Baseline was defined as the pre-dose value on Day 1 of treatment period 1.
|
Baseline and Day 8 of either treatment period 1 or 2, as applicable.
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Chair: Colin Reisner, MD, Pearl Therapeutics
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 9, 2016
Primary Completion (Actual)
June 6, 2018
Study Completion (Actual)
June 6, 2018
Study Registration Dates
First Submitted
January 28, 2016
First Submitted That Met QC Criteria
February 12, 2016
First Posted (Estimate)
February 18, 2016
Study Record Updates
Last Update Posted (Actual)
August 28, 2019
Last Update Submitted That Met QC Criteria
August 12, 2019
Last Verified
August 1, 2019
More Information
Terms related to this study
Other Study ID Numbers
- PT003017
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Yes
IPD Plan Description
AstraZeneca's policy is to share data with researchers if the request is in scope of our policy.
The policy and additional information can be found on astrazenecaclinicaltrials.com.
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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