Study to Evaluate Sex Differences in the Acute Effects of PL-3994 in Heart Failure Subjects
Primary Purpose
Heart Failure With Preserved Ejection Fraction
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
PL-3994 Aqueous Intravenous Solution Dose Ascention
PL-3994 Aqueous Intravenous Solution Single Dose
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure With Preserved Ejection Fraction focused on measuring Heart Failure, Ejection Fraction
Eligibility Criteria
Inclusion Criteria:
- The subject has provided written informed consent.
- Pre- or post-menopausal female or male age > 21 years
- LVEF ≥ 45% by echocardiography within prior 6 months
- Symptoms of HF requiring treatment with diuretics for ≥ 30 days prior to enrollment
- Current symptoms of HF (NYHA class II-IV) at time of enrollment
- 6. The subject has clinical indication for right heart catheterization for evaluation of HFpEF
- 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.
- Orthostatic hypotension, systolic blood pressure <100 mm Hg, diastolic blood pressure < 50 mmHg.
- Any prior echocardiogram with LVEF < 40%
- Hemoglobin < 9 g/dl
- eGFR < 30 mL/min/1.73 m2
- Hemodynamically significant arrhythmias within prior 4 weeks
- Acute coronary syndrome, cardiac surgery, or percutaneous coronary intervention within prior 3 months
- 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
- Current need for IV inotropic medication
- Currently taking nitrates or having stopped nitrates within 24 hours of visit
- 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
- Currently hospitalized for HF
- Any prior need for mechanical circulatory support
- Previous adverse reaction to the study drug
- Inability to comply with planned study procedures
- Pregnant or nursing mothers
- Participation in another study with an investigational drug or device within 30 days or a biologic study within 90 days prior to signing consent.
- 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.
Sites / Locations
- Northwestern UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Part A: PL-3994 Dose Ascension
Part B: PL-3994 Single Dose
Arm Description
Dose ascension: up to 15 subjects with HFpEF. N = 3 per dose level, up to 5 dose levels.
Up to 40 subjects with HFpEF (20 Females, 20 Males) will receive a single dose of PL-3994.
Outcomes
Primary Outcome Measures
Part A: Dose Ascension
Reaching the maximum tolderated dose (MTD) as defined by meeting stopping criteria.
Part B: Coronary Sinus Levels
Coronary sinus levels of cGMP post PL-3994 infusion as compared to baseline.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT04318145
First Posted
March 16, 2020
Last Updated
December 13, 2021
Sponsor
Palatin Technologies, Inc
1. Study Identification
Unique Protocol Identification Number
NCT04318145
Brief Title
Study to Evaluate Sex Differences in the Acute Effects of PL-3994 in Heart Failure Subjects
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Recruiting
Study Start Date
November 12, 2020 (Actual)
Primary Completion Date
March 31, 2022 (Anticipated)
Study Completion Date
March 31, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Palatin Technologies, Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Preserved Ejection Fraction
Keywords
Heart Failure, Ejection Fraction
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
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.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
55 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Part A: PL-3994 Dose Ascension
Arm Type
Experimental
Arm Description
Dose ascension: up to 15 subjects with HFpEF. N = 3 per dose level, up to 5 dose levels.
Arm Title
Part B: PL-3994 Single Dose
Arm Type
Experimental
Arm Description
Up to 40 subjects with HFpEF (20 Females, 20 Males) will receive a single dose of PL-3994.
Intervention Type
Drug
Intervention Name(s)
PL-3994 Aqueous Intravenous Solution Dose Ascention
Other Intervention Name(s)
PL-3994
Intervention Description
Following appropriate dilution, PL-3994 will be injected intravenously by site personnel as a bolus dose followed by continuous infusion
Intervention Type
Drug
Intervention Name(s)
PL-3994 Aqueous Intravenous Solution Single Dose
Other Intervention Name(s)
PL-3994
Intervention Description
Following appropriate dilution, PL-3994 will be injected intravenously by site personnel as a bolus dose followed by continuous infusion
Primary Outcome Measure Information:
Title
Part A: Dose Ascension
Description
Reaching the maximum tolderated dose (MTD) as defined by meeting stopping criteria.
Time Frame
1 day
Title
Part B: Coronary Sinus Levels
Description
Coronary sinus levels of cGMP post PL-3994 infusion as compared to baseline.
Time Frame
1 day
Secondary Outcome Measure Information:
Title
Part B: Blood pressure measured in mmHg
Description
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
Title
Part B: Heart rate measured in beats per minute
Description
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
Title
Part B: Right atrial pressure measured in mmHg
Description
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
Title
Part B: Pulmonary artery pressure measured in mmHg
Description
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
Title
Part B: Pulmonary capillary wedge pressure measured in mmHg
Description
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
Title
Part B: Cardiac output measured in L/min.
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The subject has provided written informed consent.
Pre- or post-menopausal female or male age > 21 years
LVEF ≥ 45% by echocardiography within prior 6 months
Symptoms of HF requiring treatment with diuretics for ≥ 30 days prior to enrollment
Current symptoms of HF (NYHA class II-IV) at time of enrollment
6. The subject has clinical indication for right heart catheterization for evaluation of HFpEF
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.
Orthostatic hypotension, systolic blood pressure <100 mm Hg, diastolic blood pressure < 50 mmHg.
Any prior echocardiogram with LVEF < 40%
Hemoglobin < 9 g/dl
eGFR < 30 mL/min/1.73 m2
Hemodynamically significant arrhythmias within prior 4 weeks
Acute coronary syndrome, cardiac surgery, or percutaneous coronary intervention within prior 3 months
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
Current need for IV inotropic medication
Currently taking nitrates or having stopped nitrates within 24 hours of visit
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
Currently hospitalized for HF
Any prior need for mechanical circulatory support
Previous adverse reaction to the study drug
Inability to comply with planned study procedures
Pregnant or nursing mothers
Participation in another study with an investigational drug or device within 30 days or a biologic study within 90 days prior to signing consent.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jason Winters
Phone
609-495-2243
Email
jwinters@palatin.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sangiv J. Shah, MD
Organizational Affiliation
Northwestern University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Northwestern University
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60208
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sanjiv J Shah, MD
Phone
312-695-0993
Email
sanjiv.shah@northwestern.edu
First Name & Middle Initial & Last Name & Degree
Ryan Sisk
Email
r-sisk@northwestern.edu
12. IPD Sharing Statement
Plan to Share IPD
No
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Study to Evaluate Sex Differences in the Acute Effects of PL-3994 in Heart Failure Subjects
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