Back to resultsA Study to Assess the Hemodynamic Effects, Safety, Tolerability, and Pharmacokinetics of Intravenous APD418 in Adult Participants With Heart Failure With Reduced Ejection Fraction
Primary Purpose
Acute Heart Failure With Reduced Ejection Fraction
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
APD418
APD418
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Acute Heart Failure With Reduced Ejection Fraction focused on measuring Heart failure with reduced ejection fraction, HFrEF, APD418, Acute Heart Failure (AHF)
Eligibility Criteria
Inclusion Criteria:
- Advanced chronic Heart Failure with Reduced Ejection Fraction (HFrEF), defined as left ventricular ejection fraction (LVEF) less than or equal to (≤) 35% at Screening, including documented history of HFrEF (LVEF ≤ 35%) for at least 4 months prior to Screening
- New York Heart Association Class II-IV
- Cardiac index ≤ 2.5 liters per minute per square meter (L/min/m^2) and pulmonary capillary wedge pressure ≥ 15 millimeters of mercury (mm Hg) at Day 1
- Body mass index 18.0 to 37.0 kilograms per square meter (kg/m^2), inclusive, and body weight < 150 kg at Screening and Day 1
Exclusion Criteria:
- Hemodynamically unstable at Day 1 or in the opinion of the Investigator likely to progress to becoming hemodynamically unstable during the course of the study
- Treated with carvedilol or at a dose higher than a total of 25 milligrams per day any time within 72 hours of Day 1 through the end of the in-clinic observation Post-dose Period.
- Receiving any mechanical (respiratory or circulatory) or renal support therapy at Screening or Day 1
- Systolic Blood Pressure ≤ 90 millimeter of mercury (mm Hg) or ≥ 160 mm Hg, or Heart Rate < 50 beats per minute (bpm) or > 110 bpm, at Screening or Day 1
- Recently treated with inotropic, intravenous (IV) vasoactive or IV diuretic therapy, or expected to require such therapy with these drugs any time from Day 1 through the end of study conduct.
Sites / Locations
- James A. Haley Veterans' Hospital
- UnityPoint Health - Methodist Hospital
- UTHealth
- Health Science Center Utah
- University of Wisconsin
- Immanuel Hospital Bernau Brandenburg Heart Center
- Kerckhoff-Klinik Forschungsgesellschaft GmbH
- Universitatsmedizin Greifwald
- Konstantinopouleio General Hospital of Nea Ionia - Patision ''Agia Olga''
- Interbalkan European Medical Center
- General University Hospital of Larissa
- American Heart of Poland S.A.
- Krakowski Szpital Specjalistyczny im. Jana Pawla II
- Uniwersytecki Szpital Kliniczny im Jana Mikulicza-Radeckiego
- Clinical Hospital Centre Zemun
- University Clinical Centre of Serbia
- Institute for Cardiovascular Diseases Dedinje
- Clinical Hospital Center Bezanijska Kosa
- Clinical Center of Kragujevac
- Institute for Cardiovascular Diseases of Vojvodina
- Healthcare Center Uzice
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
APD418 (Part A: Dose Cohort 1-5)
APD418 (Part B: Dose Group 1 and 2)
Placebo (Part A: Cohort 1-5 and Part B)
Arm Description
Outcomes
Primary Outcome Measures
Change From Baseline in Cardiac Index Measured by Right Heart Catheterization (RHC)
Secondary Outcome Measures
Change From Baseline in Cardiac Output Measured by RHC
Change From Baseline in Pulmonary Capillary Wedge Pressure Measured by RHC
Change From Baseline in Right Atrial Pressure Measured by RHC
Change From Baseline in Systolic and Diastolic Pulmonary Arterial Pressure Measured by RHC
Change From Baseline in Pulmonary Artery Pulsatility Index Measured by RHC
Change From Baseline in Systemic Vascular Resistance and Systemic Vascular Resistance Index Measured by RHC
Change From Baseline in Pulmonary Vascular Resistance Measured by RHC
Change From Baseline in Systolic Blood Pressure
Change From Baseline in Diastolic Blood Pressure
Change From Baseline in Mean Arterial Pressure
Change From Baseline in Heart Rate
Change From Baseline in Stroke Volume Measured by Echocardiogram (ECHO)
Change From Baseline in Stroke Volume Index Measured by ECHO
Change From Baseline in Left Ventricular Ejection Fraction Measured by ECHO
Change From Baseline in Fractional Shortening Measured by ECHO
Change From Baseline in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Volume Measured by ECHO
Change From Baseline in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO
Change From Baseline in Left Ventricular Global Longitudinal Strain Measured by ECHO
Change From Baseline in Left Ventricular Global Circumferential Strain Measured by ECHO
Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours (AUC0-6) of APD418
Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Plasma Concentration (AUClast) of APD418
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of APD418
Maximum Observed Plasma Concentration (Cmax) of APD418
Terminal Elimination Half-life (t1/2) of APD418
Distribution Half-life (t1/2α) of APD418
Time to Maximum Observed Plasma Concentration (tmax) of APD418
Total Clearance (CL) of APD418
Volume of Distribution Based on the Terminal Phase (Vdz) of APD418
Volume of Distribution at Steady State (Vdss) of APD418
Mean Residence Time From Time 0 to Time of Last Quantifiable Plasma Concentration (MRTlast) of APD418
Average Plasma Concentration During the Dosing Interval (Cave) of APD418
Amount of Unchanged Drug Excreted in Urine During Each Collection Interval From t1 to t2 (Aet1-t2)
Total Amount of Unchanged Drug Excreted in Urine Over the Collection Period (Amount Excreted [Ae])
Renal Clearance (CLr) of APD418
Fraction of Drug Excreted Unchanged in Urine, Expressed as a Percentage of Total Dose (Fraction Excreted [Fe])
Number and Severity of Adverse Events
Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results.
Full Information
NCT ID
NCT05139615
First Posted
November 18, 2021
Last Updated
September 20, 2022
Sponsor
Arena Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05139615
Brief Title
A Study to Assess the Hemodynamic Effects, Safety, Tolerability, and Pharmacokinetics of Intravenous APD418 in Adult Participants With Heart Failure With Reduced Ejection Fraction
Official Title
A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Hemodynamic Effects, Safety, Tolerability, and Pharmacokinetics of APD418 in Subjects With Heart Failure With Reduced Ejection Fraction
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Terminated
Why Stopped
Business decision
Study Start Date
December 28, 2021 (Actual)
Primary Completion Date
September 19, 2022 (Actual)
Study Completion Date
September 19, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Arena Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety, pharmacokinetics, and effect on cardiac function of intravenous APD418 in adult participants with heart failure with reduced ejection fraction (HFrEF).
Detailed Description
This study has an adaptive design, in which dose escalation in Part A will inform dose expansion in Part B. Part A is a single-ascending dose, placebo-controlled study planned to consist of 5 cohorts evaluating 5 doses of APD418. Part B is a parallel-treatment group study planned to evaluate 2 doses of APD418 and placebo. Participants in Part A cannot participate in Part B.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Heart Failure With Reduced Ejection Fraction
Keywords
Heart failure with reduced ejection fraction, HFrEF, APD418, Acute Heart Failure (AHF)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
APD418 (Part A: Dose Cohort 1-5)
Arm Type
Experimental
Arm Title
APD418 (Part B: Dose Group 1 and 2)
Arm Type
Experimental
Arm Title
Placebo (Part A: Cohort 1-5 and Part B)
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
APD418
Intervention Description
Participants will receive a single dose of APD418 as an intravenous (IV) infusion.
Intervention Type
Drug
Intervention Name(s)
APD418
Intervention Description
Participants will receive a single dose of APD418 as an IV infusion.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will receive a single dose of APD418 matching placebo as an IV infusion.
Primary Outcome Measure Information:
Title
Change From Baseline in Cardiac Index Measured by Right Heart Catheterization (RHC)
Time Frame
Baseline to end of intravenous (IV) infusion at 6 hours
Secondary Outcome Measure Information:
Title
Change From Baseline in Cardiac Output Measured by RHC
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Pulmonary Capillary Wedge Pressure Measured by RHC
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Right Atrial Pressure Measured by RHC
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Systolic and Diastolic Pulmonary Arterial Pressure Measured by RHC
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Pulmonary Artery Pulsatility Index Measured by RHC
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Systemic Vascular Resistance and Systemic Vascular Resistance Index Measured by RHC
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Pulmonary Vascular Resistance Measured by RHC
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Systolic Blood Pressure
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Diastolic Blood Pressure
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Mean Arterial Pressure
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Heart Rate
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Stroke Volume Measured by Echocardiogram (ECHO)
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Stroke Volume Index Measured by ECHO
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Left Ventricular Ejection Fraction Measured by ECHO
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Fractional Shortening Measured by ECHO
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Volume Measured by ECHO
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Left Ventricular Global Longitudinal Strain Measured by ECHO
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Change From Baseline in Left Ventricular Global Circumferential Strain Measured by ECHO
Time Frame
Baseline to end of IV infusion at 6 hours
Title
Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours (AUC0-6) of APD418
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Plasma Concentration (AUClast) of APD418
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of APD418
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Maximum Observed Plasma Concentration (Cmax) of APD418
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Terminal Elimination Half-life (t1/2) of APD418
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Distribution Half-life (t1/2α) of APD418
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Time to Maximum Observed Plasma Concentration (tmax) of APD418
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Total Clearance (CL) of APD418
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Volume of Distribution Based on the Terminal Phase (Vdz) of APD418
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Volume of Distribution at Steady State (Vdss) of APD418
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Mean Residence Time From Time 0 to Time of Last Quantifiable Plasma Concentration (MRTlast) of APD418
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Average Plasma Concentration During the Dosing Interval (Cave) of APD418
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Amount of Unchanged Drug Excreted in Urine During Each Collection Interval From t1 to t2 (Aet1-t2)
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Total Amount of Unchanged Drug Excreted in Urine Over the Collection Period (Amount Excreted [Ae])
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Renal Clearance (CLr) of APD418
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Fraction of Drug Excreted Unchanged in Urine, Expressed as a Percentage of Total Dose (Fraction Excreted [Fe])
Time Frame
Intermediate timepoints during 6-hour infusion
Title
Number and Severity of Adverse Events
Description
Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results.
Time Frame
Up to Study Day 9
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Advanced chronic Heart Failure with Reduced Ejection Fraction (HFrEF), defined as left ventricular ejection fraction (LVEF) less than or equal to (≤) 35% at Screening, including documented history of HFrEF (LVEF ≤ 35%) for at least 4 months prior to Screening
New York Heart Association Class II-IV
Cardiac index ≤ 2.5 liters per minute per square meter (L/min/m^2) and pulmonary capillary wedge pressure ≥ 15 millimeters of mercury (mm Hg) at Day 1
Body mass index 18.0 to 37.0 kilograms per square meter (kg/m^2), inclusive, and body weight < 150 kg at Screening and Day 1
Exclusion Criteria:
Hemodynamically unstable at Day 1 or in the opinion of the Investigator likely to progress to becoming hemodynamically unstable during the course of the study
Treated with carvedilol or at a dose higher than a total of 25 milligrams per day any time within 72 hours of Day 1 through the end of the in-clinic observation Post-dose Period.
Receiving any mechanical (respiratory or circulatory) or renal support therapy at Screening or Day 1
Systolic Blood Pressure ≤ 90 millimeter of mercury (mm Hg) or ≥ 160 mm Hg, or Heart Rate < 50 beats per minute (bpm) or > 110 bpm, at Screening or Day 1
Recently treated with inotropic, intravenous (IV) vasoactive or IV diuretic therapy, or expected to require such therapy with these drugs any time from Day 1 through the end of study conduct.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Arena CT.gov Administrator
Organizational Affiliation
Arena Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
James A. Haley Veterans' Hospital
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
UnityPoint Health - Methodist Hospital
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61606
Country
United States
Facility Name
UTHealth
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Health Science Center Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Immanuel Hospital Bernau Brandenburg Heart Center
City
Bernau bei Berlin
State/Province
Brandenburg
ZIP/Postal Code
16321
Country
Germany
Facility Name
Kerckhoff-Klinik Forschungsgesellschaft GmbH
City
Bad Nauheim
ZIP/Postal Code
61231
Country
Germany
Facility Name
Universitatsmedizin Greifwald
City
Greifswald
ZIP/Postal Code
17475
Country
Germany
Facility Name
Konstantinopouleio General Hospital of Nea Ionia - Patision ''Agia Olga''
City
Nea Ionia
State/Province
Athens
ZIP/Postal Code
14233
Country
Greece
Facility Name
Interbalkan European Medical Center
City
Pylaia
State/Province
Thessaloniki
ZIP/Postal Code
55535
Country
Greece
Facility Name
General University Hospital of Larissa
City
Larissa
ZIP/Postal Code
41110
Country
Greece
Facility Name
American Heart of Poland S.A.
City
Gniezno
ZIP/Postal Code
62-200
Country
Poland
Facility Name
Krakowski Szpital Specjalistyczny im. Jana Pawla II
City
Krakow
ZIP/Postal Code
31-202
Country
Poland
Facility Name
Uniwersytecki Szpital Kliniczny im Jana Mikulicza-Radeckiego
City
Wroclaw
ZIP/Postal Code
50-556
Country
Poland
Facility Name
Clinical Hospital Centre Zemun
City
Belgrade
ZIP/Postal Code
11 070
Country
Serbia
Facility Name
University Clinical Centre of Serbia
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Institute for Cardiovascular Diseases Dedinje
City
Belgrade
ZIP/Postal Code
11040
Country
Serbia
Facility Name
Clinical Hospital Center Bezanijska Kosa
City
Belgrade
ZIP/Postal Code
11080
Country
Serbia
Facility Name
Clinical Center of Kragujevac
City
Kragujevac
ZIP/Postal Code
34000
Country
Serbia
Facility Name
Institute for Cardiovascular Diseases of Vojvodina
City
Sremska Kamenica
ZIP/Postal Code
21204
Country
Serbia
Facility Name
Healthcare Center Uzice
City
Užice
ZIP/Postal Code
31000
Country
Serbia
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Study to Assess the Hemodynamic Effects, Safety, Tolerability, and Pharmacokinetics of Intravenous APD418 in Adult Participants With Heart Failure With Reduced Ejection Fraction
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