A Multi-Center, Unblinded, Single-Arm Study to Evaluate Sex Differences in the Acute Effects of PL-3994 on Myocardial cGMP Enhancement and Hemodynamics in Heart Failure with Preserved Ejection Fraction
Multi-center, unblinded, dose ascending, two-part pilot study involving Part A, up to 15 subjects for dose ascension and optimization (N=3 per dose level, up to 5 dose levels) and Part B, 40 patients (n=20 women, n=20 men), with a single dose of PL-3994 after which hemodynamics will be measured by pulmonary artery catheter and pulmonary artery (mixed venous) and coronary sinus blood sampling will be performed to measure cGMP levels during a 15-minute observation period. The objective of this study is to evaluate the acute effects of a single dose of intravenous PL-3994 on hemodynamics and myocardial cGMP expression. The following endpoints will be assessed: * Hemodynamics (including blood pressure, right atrial pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output) * Myocardial cGMP expression via coronary sinus sampling
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
15
Following appropriate dilution, PL-3994 will be injected intravenously by site personnel as a bolus dose followed by continuous infusion
Following appropriate dilution, PL-3994 will be injected intravenously by site personnel as a bolus dose followed by continuous infusion
Northwestern University
Evanston, Illinois, United States
Part A: Dose Ascension
Reaching the maximum tolderated dose (MTD) as defined by meeting stopping criteria.
Time frame: 1 day
Part B: Coronary Sinus Levels
Coronary sinus levels of cGMP post PL-3994 infusion as compared to baseline.
Time frame: 1 day
Part B: Blood pressure measured in mmHg
Measured at baseline (t=0) and at t=3, 6, 9, 12, and 15 minutes after the infusion of study drug.
Time frame: 1 day
Part B: Heart rate measured in beats per minute
Measured at baseline (t=0) and at t=3, 6, 9, 12, and 15 minutes after the infusion of study drug.
Time frame: 1 day
Part B: Right atrial pressure measured in mmHg
Measured at baseline (t=0) and at t=3, 6, 9, 12, and 15 minutes after the infusion of study drug.
Time frame: 1 day
Part B: Pulmonary artery pressure measured in mmHg
Measured at baseline (t=0) and at t=3, 6, 9, 12, and 15 minutes after the infusion of study drug.
Time frame: 1 day
Part B: Pulmonary capillary wedge pressure measured in mmHg
Measured at baseline (t=0) and at t=3, 6, 9, 12, and 15 minutes after the infusion of study drug.
Time frame: 1 day
Part B: Cardiac output measured in L/min.
Measured at baseline (t=0) and at t=3, 6, 9, 12, and 15 minutes after the infusion of study drug.
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Time frame: 1 day