Study to Evaluate Sex Differences in the Acute Effects of PL-3994 in Heart Failure Subjects

Heart Failure With Preserved Ejection Fraction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04318145
• Other study ID #: PL-3994-701
• Status: Recruiting
• Phase: Phase 2
• Start date: November 12, 2020
• Est. completion date: March 31, 2023

Study information

• Verified date: December 2021
• Source: Palatin Technologies
• Contact: Jason Winters
• Phone: 609-495-2243
• Email: jwinters[@]palatin.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 55
• Est. completion date: March 31, 2023
• Est. primary completion date: March 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

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 exclusion criteria must not be enrolled.

1. Orthostatic hypotension, systolic blood pressure <100 mm Hg, diastolic blood pressure < 50 mmHg.

2. Any prior echocardiogram with LVEF < 40%

3. Hemoglobin < 9 g/dl

4. eGFR < 30 mL/min/1.73 m2

5. Hemodynamically significant arrhythmias within prior 4 weeks

6. Acute coronary syndrome, cardiac surgery, or percutaneous coronary intervention within prior 3 months

7. Any of the following cardiac diagnoses: active myocarditis, hypertrophic cardiomyopathy, > moderate regurgitant valvular disease, any valvular stenosis, restrictive cardiomyopathy (including amyloid, sarcoid, or hemochromatosis), constrictive pericarditis, complex congenital heart disease, or pulmonary arterial hypertension

8. Current need for IV inotropic medication

9. Currently taking nitrates or having stopped nitrates within 24 hours of visit

10. Currently taking antihistamines, antipsychotics, tri-cyclic antidepressants, catecholamines/related compounds, monoamine oxidase inhibitors, stimulants (including caffeine and nicotine), sympathomimetics, dopamine agonists. Additionally, medications that inhibit PDE activity will be prohibited during the study and for 5 half- lives prior to Day 1 so that cGMP measurements will not be affected

11. Currently hospitalized for HF

12. Any prior need for mechanical circulatory support

13. Previous adverse reaction to the study drug

14. Inability to comply with planned study procedures

15. Pregnant or nursing mothers

16. Participation in another study with an investigational drug or device within 30 days or a biologic study within 90 days prior to signing consent.

17. Study participants must use method of birth control that has been approved by the Study Doctor and males must not donate sperm during the study and for 30 days after the last dose of study drug.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction

Intervention

Drug:
• PL-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
• PL-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

Locations

Country	Name	City	State
United States	Northwestern University	Evanston	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Palatin Technologies

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part A: Dose Ascension	Reaching the maximum tolderated dose (MTD) as defined by meeting stopping criteria.	1 day
Primary	Part B: Coronary Sinus Levels	Coronary sinus levels of cGMP post PL-3994 infusion as compared to baseline.	1 day
Secondary	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.	1 day
Secondary	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.	1 day
Secondary	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.	1 day
Secondary	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.	1 day
Secondary	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.	1 day
Secondary	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.	1 day