Heart Failure With Preserved Ejection Fraction
Conditions
Keywords
Heart Failure, Ejection Fraction
Brief summary
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
Detailed description
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
Interventions
DRUGPL-3994 Aqueous Intravenous Solution Dose Ascention
Following appropriate dilution, PL-3994 will be injected intravenously by site personnel as a bolus dose followed by continuous infusion
DRUGPL-3994 Aqueous Intravenous Solution Single Dose
Following appropriate dilution, PL-3994 will be injected intravenously by site personnel as a bolus dose followed by continuous infusion
Sponsors
Palatin Technologies, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part A: Single dose per subject, dose level ascension every 3 subjects. 5 dose levels are planned. An intermediate dose between planned doses may be chosen by the Sponsor/Investigator upon discussion after MTD is reached. Part B: Single dose, dose chosen from Part A.
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. The subject has provided written informed consent. 2. Pre- or post-menopausal female or male age \> 21 years 3. LVEF ≥ 45% by echocardiography within prior 6 months 4. Symptoms of HF requiring treatment with diuretics for ≥ 30 days prior to enrollment 5. Current symptoms of HF (NYHA class II-IV) at time of enrollment 6. 6\. The subject has clinical indication for right heart catheterization for evaluation of HFpEF 7. Negative pregnancy test in a female of childbearing potential
Exclusion criteria
* A subject who meets ANY of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Dose Ascension | 1 day | Reaching the maximum tolderated dose (MTD) as defined by meeting stopping criteria. |
| Part B: Coronary Sinus Levels | 1 day | Coronary sinus levels of cGMP post PL-3994 infusion as compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Right atrial pressure measured in mmHg | 1 day | Measured at baseline (t=0) and at t=3, 6, 9, 12, and 15 minutes after the infusion of study drug. |
| Part B: Pulmonary artery pressure measured in mmHg | 1 day | Measured at baseline (t=0) and at t=3, 6, 9, 12, and 15 minutes after the infusion of study drug. |
| Part B: Blood pressure measured in mmHg | 1 day | Measured at baseline (t=0) and at t=3, 6, 9, 12, and 15 minutes after the infusion of study drug. |
| Part B: Cardiac output measured in L/min. | 1 day | Measured at baseline (t=0) and at t=3, 6, 9, 12, and 15 minutes after the infusion of study drug. |
| Part B: Pulmonary capillary wedge pressure measured in mmHg | 1 day | Measured at baseline (t=0) and at t=3, 6, 9, 12, and 15 minutes after the infusion of study drug. |
| Part B: Heart rate measured in beats per minute | 1 day | Measured at baseline (t=0) and at t=3, 6, 9, 12, and 15 minutes after the infusion of study drug. |
Countries
United States
Outcome results
None listed