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A Study to Assess the Hemodynamic Effects, Safety, Tolerability, and Pharmacokinetics of Intravenous APD418 in Adult Participants With Heart Failure With Reduced Ejection Fraction

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05139615
Recruitment Status : Recruiting
First Posted : December 1, 2021
Last Update Posted : August 9, 2022
Sponsor:
Information provided by (Responsible Party):
Arena Pharmaceuticals

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).

Condition or disease Intervention/treatment Phase
Acute Heart Failure With Reduced Ejection Fraction Drug: APD418 Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : December 28, 2021
Estimated Primary Completion Date : March 2023
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Failure

Arm Intervention/treatment
Experimental: APD418 (Part A: Dose Cohort 1-5) Drug: APD418
Participants will receive a single dose of APD418 as an intravenous (IV) infusion.

Experimental: APD418 (Part B: Dose Group 1 and 2) Drug: APD418
Participants will receive a single dose of APD418 as an IV infusion.

Placebo Comparator: Placebo (Part A: Cohort 1-5 and Part B) Drug: Placebo
Participants will receive a single dose of APD418 matching placebo as an IV infusion.




Primary Outcome Measures :
  1. 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 Measures :
  1. Change From Baseline in Cardiac Output Measured by RHC [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  2. Change From Baseline in Pulmonary Capillary Wedge Pressure Measured by RHC [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  3. Change From Baseline in Right Atrial Pressure Measured by RHC [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  4. Change From Baseline in Systolic and Diastolic Pulmonary Arterial Pressure Measured by RHC [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  5. Change From Baseline in Pulmonary Artery Pulsatility Index Measured by RHC [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  6. 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 ]
  7. Change From Baseline in Pulmonary Vascular Resistance Measured by RHC [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  8. Change From Baseline in Systolic Blood Pressure [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  9. Change From Baseline in Diastolic Blood Pressure [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  10. Change From Baseline in Mean Arterial Pressure [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  11. Change From Baseline in Heart Rate [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  12. Change From Baseline in Stroke Volume Measured by Echocardiogram (ECHO) [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  13. Change From Baseline in Stroke Volume Index Measured by ECHO [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  14. Change From Baseline in Left Ventricular Ejection Fraction Measured by ECHO [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  15. Change From Baseline in Fractional Shortening Measured by ECHO [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  16. 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 ]
  17. 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 ]
  18. Change From Baseline in Left Ventricular Global Longitudinal Strain Measured by ECHO [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  19. Change From Baseline in Left Ventricular Global Circumferential Strain Measured by ECHO [ Time Frame: Baseline to end of IV infusion at 6 hours ]
  20. 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 ]
  21. 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 ]
  22. Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-∞) of APD418 [ Time Frame: Intermediate timepoints during 6-hour infusion ]
  23. Maximum Observed Plasma Concentration (Cmax) of APD418 [ Time Frame: Intermediate timepoints during 6-hour infusion ]
  24. Terminal Elimination Half-life (t1/2) of APD418 [ Time Frame: Intermediate timepoints during 6-hour infusion ]
  25. Distribution Half-life (t1/2α) of APD418 [ Time Frame: Intermediate timepoints during 6-hour infusion ]
  26. Time to Maximum Observed Plasma Concentration (tmax) of APD418 [ Time Frame: Intermediate timepoints during 6-hour infusion ]
  27. Total Clearance (CL) of APD418 [ Time Frame: Intermediate timepoints during 6-hour infusion ]
  28. Volume of Distribution Based on the Terminal Phase (Vdz) of APD418 [ Time Frame: Intermediate timepoints during 6-hour infusion ]
  29. Volume of Distribution at Steady State (Vdss) of APD418 [ Time Frame: Intermediate timepoints during 6-hour infusion ]
  30. Mean Residence Time From Time 0 to Time of Last Quantifiable Plasma Concentration (MRTlast) of APD418 [ Time Frame: Intermediate timepoints during 6-hour infusion ]
  31. Average Plasma Concentration During the Dosing Interval (Cave) of APD418 [ Time Frame: Intermediate timepoints during 6-hour infusion ]
  32. 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 ]
  33. Total Amount of Unchanged Drug Excreted in Urine Over the Collection Period (Amount Excreted [Ae]) [ Time Frame: Intermediate timepoints during 6-hour infusion ]
  34. Renal Clearance (CLr) of APD418 [ Time Frame: Intermediate timepoints during 6-hour infusion ]
  35. 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 ]
  36. Number and Severity of Adverse Events [ Time Frame: Up to Study Day 9 ]
    Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05139615


Contacts
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Contact: Arena CT.gov Administrator +1 855-218-9153 ct.gov@arenapharm.com

Locations
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Sponsors and Collaborators
Arena Pharmaceuticals
Investigators
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Study Director: Arena CT.gov Administrator Arena Pharmaceuticals
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Responsible Party: Arena Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05139615    
Other Study ID Numbers: APD418-201
First Posted: December 1, 2021    Key Record Dates
Last Update Posted: August 9, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Arena Pharmaceuticals:
Heart failure with reduced ejection fraction
HFrEF
APD418
Acute Heart Failure (AHF)
Additional relevant MeSH terms:
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Heart Failure
Heart Diseases
Cardiovascular Diseases