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

NCT ID: NCT04318145

Last Updated: 2021-12-14

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-12
• Study Completion Date: 2023-03-31

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

Conditions

Heart Failure With Preserved Ejection Fraction

Keywords

Heart Failure, Ejection Fraction

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: PL-3994 Dose Ascension

Dose ascension: up to 15 subjects with HFpEF. N = 3 per dose level, up to 5 dose levels.

Group Type: EXPERIMENTAL

PL-3994 Aqueous Intravenous Solution Dose Ascention

Intervention Type: DRUG

Following appropriate dilution, PL-3994 will be injected intravenously by site personnel as a bolus dose followed by continuous infusion

Part B: PL-3994 Single Dose

Up to 40 subjects with HFpEF (20 Females, 20 Males) will receive a single dose of PL-3994.

Group Type: EXPERIMENTAL

PL-3994 Aqueous Intravenous Solution Single Dose

Intervention Type: DRUG

Following appropriate dilution, PL-3994 will be injected intravenously by site personnel as a bolus dose followed by continuous infusion

Interventions

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Other Intervention Names

PL-3994; PL-3994

Eligibility Criteria

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

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.

• Minimum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Palatin Technologies, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sangiv J. Shah, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University Medical Center

Locations

Northwestern University

Evanston, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jason Winters

Role: CONTACT

Phone: 609-495-2243

Email: jwinters@palatin.com

Facility Contacts

Sanjiv J Shah, MD

Role: primary

Ryan Sisk

Role: backup

Other Identifiers

PL-3994-701

Identifier Type: -

Identifier Source: org_study_id