Clinical trial NCT02685293: Study to Evaluate the Treatment Effect of PT003 on Cardiovascular Hemodynamics in Subjects With Moderate to Severe COPD
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: COPD
Lead sponsor: Pearl Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2016-02-18
Enrollment: 4
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change From Baseline in Right Ventricular End Diastolic Volume Index (RVEDVi) at 2-3 Hours Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
Secondary outcomes:
measure: Change From Baseline in Aortic Left Ventricular Stroke Volume (LVSV) at 2-3 Hours Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
measure: Change From Baseline in Right Ventricular Stroke Volume (RVSV) at 2-3 Hours Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
measure: Change From Baseline in Pulmonary Artery Velocity at 2-3 Hours Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
measure: Change From Baseline in Left Ventricular End Diastolic Volume Index (LVEDVi) at 2-3 Hours Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
measure: Change From Baseline in Cardiac Output at 2-3 Hours Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
measure: Change From Baseline in Pulmonary Vascular Resistance (PVR) at 30 and 60 Minutes Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
measure: Change From Baseline in Pulmonary Artery/Aortic Diameter Ratio (PA:A) at 2-3 Hours Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
measure: Change From Baseline in Left Atrial End Diastolic Volume (LAEDV) at 2-3 Hours Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
measure: Change From Baseline in Left Atrial End Systolic Volume (LAESV) at 2-3 Hours Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
measure: Change From Baseline in Left Atrial Ejection Fraction (LAEF) at 2-3 Hours Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
measure: Change From Baseline in Left Ventricular End Systolic Volume Index (LVESVi) at 2-3 Hours Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
measure: Change From Baseline in Right Ventricular End Systolic Volume Index (RVESVi) at 2-3 Hours Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
measure: Change From Baseline in Pulsatility Index Aorta (PIAo) at 2-3 Hours Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
measure: Change From Baseline in Pulmonary Artery Pulsatility Index (PAPi) at 2-3 Hours Post-dose on Day 8
timeFrame: Baseline and Day 8 of either treatment period 1 or 2, as applicable.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
Study officials:
affiliation: Pearl Therapeutics
name: Colin Reisner, MD
role: STUDY_CHAIR
References: