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

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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT05139615

Enrollment

Registered

2021-12-01

Start date

2021-12-28

Completion date

2022-09-19

Last updated

2023-11-09

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Heart Failure With Reduced Ejection Fraction

Keywords

Heart failure with reduced ejection fraction, HFrEF, APD418, Acute Heart Failure (AHF)

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.

Interventions

DRUGAPD418

Participants will receive a single dose of APD418 as an intravenous (IV) infusion.

DRUGPlacebo

Participants will receive a single dose of APD418 matching placebo as an IV infusion.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 85 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Part A: Change in Cardiac Index (CI) Measured by Right Heart Catheterization (RHC) From Baseline to End of Intravenous (IV) Infusion at 6 Hours	Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)	Cardiac index (CI) is a hemodynamic parameter that relates the cardiac output (CO) from left ventricle in one minute to body surface area (BSA), thus relating heart performance to the body size of the participant. It was measured by RHC.

Secondary

Measure	Time frame	Description
Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion	SBP, DBP and MAP were measured in a supine or seated position after participant had at least 5 minutes of rest. MAP is the average pressure of the blood circulating through a participant's arteries during the cardiac cycle. MAP was derived by using the following formula: DBP + 1/3(SBP-DBP).
Part A: Mean Residence Time From Time Zero to Time of Last Quantifiable Plasma Concentration (MRTlast) for APD418	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start	MRTlast of APD418 was reported in this outcome measure.
Part A: Average Plasma Concentration During Dosing Interval (Cave) for ADP418	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6 hours post infusion start	Average plasma concentration calculated over the 6-hour infusion time was reported in this outcome measure.
Part A: Renal Clearance (CLr) for ADP418	Pre-dose (0) to 24 hours post infusion start, collected over 0 to 6 hour, 6 to 10 hour and 10 to 24-hour intervals	CLr for APD418 was reported in this outcome measure.
Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours	Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)	SV is the volume of blood pumped from the left ventricle per beat. LVESV is the volume of blood in the left ventricle at the end of contraction and at diastole. LVEDV is the amount of blood in the heart's left ventricle just before the heart contracts. All these parameters were measured by ECHO.
Part A: Change in Stroke Volume Index (SVI) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)	SVI was calculated as stroke volume divided by BSA. This was measured by ECHO.
Part A: Change in Left Ventricular Ejection Fraction (LVEF) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)	LVEF is the central measure of left ventricular systolic function. LVEF is the fraction of chamber volume ejected in systole (stroke volume) in relation to the volume of the blood in the ventricle at the end of diastole (end-diastolic volume). This was measured by ECHO.
Part A: Change in Fractional Shortening (FS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)	FS was calculated by measuring the percentage reduction in left ventricular diameter during systole. This was measured by ECHO.
Part A: Change in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)	Left ventricular end-systolic diameter and left ventricular end-diastolic diameter were measured using ECHO.
Part A: Change in Left Ventricular Global Longitudinal Strain (LVGLS) and Left Ventricular Global Circumferential Strain (LVGCS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)	Left ventricular global strain is the average strain of the cardiac chamber wall, where LVGLS presents longitudinal shortening as a percentage (change in length as a proportion to baseline length). LVGCS measures the chamber deformation along the circumference of the cardiac wall in a tangential xy-direction and similarly presents the circumferential shortening as a percentage. Both the parameters were measured by ECHO.
Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4 and 5 hours of IV infusion	CI is a hemodynamic parameter that relates the CO from left ventricle in one minute to BSA, thus relating heart performance to the body size of the participant. It was measured by RHC.
Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion	Change in CO measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 hours during the 6-hour IV infusion was reported in this outcome measure.
Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion	PCWP estimated the left atrial pressure and was the pressure measured by wedging a pulmonary artery catheter with an inflated balloon into a small pulmonary arterial branch. PCWP was assessed by 2 successive measurements at least 10 minutes apart. RAP is the blood pressure in the right atrium of the heart. Change in PCWP, RAP, PAS/PAD at 0.5, 1, 2, 3, 4, 5 and 6 hours during the 6-hour IV infusion was reported in this outcome measure. All the parameters were measured by RHC.
Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion	PAPi is a hemodynamic parameter that is derived from right atrial and pulmonary artery pulse pressures. PAPi = (PAS - PAD)/right atrial pressure. Change in PAPi measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 hours during the 6-hour IV infusion was reported in this outcome measure.
Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion	Systemic vascular resistance (SVR) is the amount of force exerted on circulating blood by the vasculature of the body. SVR was calculated as 80\*(mean arterial pressure - mean venous pressure) divided by cardiac output. Change in SVR measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 hours during the 6-hour IV infusion was reported in this outcome measure.
Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion	SVRI was calculated by dividing the difference between mean arterial pressure and central venous pressure by cardiac index and multiplying by 80. Change in SVRI measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 hours during the 6 hour IV infusion was reported in this outcome measure.
Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion	PVR is the resistance against blood flow from the pulmonary artery to the left atrium. Change in PVR measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 hours during the 6 hour IV infusion was reported in this outcome measure.
Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion	Heart rate was measured in a supine or seated position after participant had at least 5 minutes of rest.
Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	From start of study treatment on Day 1 up to Day 9	An AE was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAEs were defined as those AEs with onset after start date/timepoint of study drug administration.
Part A: Area Under the Plasma Concentration Time Curve From Time Zero to 6 Hours (AUC[0-6]) of APD418	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6 hours post infusion start	AUC \[0-6\] was reported in this outcome measure.
Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUCLast) of APD418	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start	AUClast was reported in this outcome measure.
Part A: Area Under the Plasma Concentration Time Curve From Time Zero up to Infinity (AUC[0-Infinity]) of APD418	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start	AUC \[0-infinity\] was reported in this outcome measure.
Part A: Maximum Observed Plasma Concentration (Cmax) of APD418	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start	Cmax of APD418 was reported in this outcome measure.
Part A: Terminal Elimination Half-Life (t1/2) for APD418	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start	Terminal t1/2 of APD418 was reported in this outcome measure.
Part A: Distributional Half-Life (t1/2a) for APD418	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start	Distributional t1/2 of APD418 was reported in this outcome measure.
Part A: Time to Maximum Observed Plasma Concentration (Tmax) for APD418	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start	Tmax of APD418 was reported in this outcome measure.
Part A: Total Clearance (CL) for APD418	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start	IV CL of APD418 was reported in this outcome measure.
Part A: Total Volume of Distribution Based on the Terminal Phase (Vdz) for APD418	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start	Vdz of APD418 was reported in this outcome measure.
Part A: Volume of Distribution at Steady State (Vdss) for APD418	Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start	Vdss of APD418 was reported in this outcome measure.

Other

Measure	Time frame	Description
Part A: Fraction of Drug Excreted Unchanged (Fe) in Urine	Pre-dose (0) to 24 hours post infusion start, collected over 0 to 6 hour, 6 to 10 hour and 10 to 24-hour intervals	Fraction of drug excreted in urine was reported in this outcome measure. Data is presented in terms of percentages.
Part A: Total Amount of Unchanged Drug Excreted in Urine Over the Collection Period (Amount Excreted [Ae])	Pre-dose (0) to 24 hours post infusion start, collected over 0 to 6 hour, 6 to 10 hour and 10 to 24-hour intervals	Total amount of unchanged drug excreted in urine over the collection period was reported in this outcome measure.
Part A: Amount of Unchanged Drug Excreted in Urine During Each Collection Interval From t1 to t2 (Aet1-t2)	Anytime between 0 to 6 hours, 6 to 10 hours and 10 to 24 hours post infusion start	Amount of unchanged drug excreted in urine during each collection interval from t1 to t2 was reported in this outcome measure.

Countries

Germany, Greece, Poland, Serbia, United States

Participant flow

Pre-assignment details

The study was planned to be conducted in two parts (Part A and B); however, study was terminated during Part A due to a business decision by Sponsor and Part B was not initiated and no participants were enrolled in Part B.

Participants by arm

Arm	Count
Cohort 1- 0.17 mg/kg/hr APD418 Participants were administered a single dose of 0.17 milligrams per kilogram per hour (mg/kg/hr) (total dose of 1 mg/kg) APD418 as an intravenous (IV) infusion over a duration of 6 hours on Day 1 (Dosing Period) followed by an 18 to 24-hour in-clinic observation period.	4
Cohort 1- Placebo Participants were administered a single dose of matching placebo as an IV infusion over a duration of 6 hours on Day 1 (Dosing Period) followed by an 18 to 24-hour in-clinic observation period.	3
Cohort 2- 0.5 mg/kg/hr APD418 Participants were administered a single dose of 0.5 mg/kg/hr (total dose of 3 mg/kg) APD418 as an IV infusion over a duration of 6 hours on Day 1 (Dosing Period) followed by an 18 to 24-hour in-clinic observation period.	11
Cohort 2- Placebo Participants were administered a single dose of matching placebo as an IV infusion over a duration of 6 hours on Day 1 (Dosing Period) followed by an 18 to 24-hour in-clinic observation period.	4
Total	22

Baseline characteristics

Characteristic	Cohort 1- 0.17 mg/kg/hr APD418	Cohort 1- Placebo	Cohort 2- 0.5 mg/kg/hr APD418	Cohort 2- Placebo	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	2 Participants	1 Participants	3 Participants	3 Participants	9 Participants
Age, Categorical Between 18 and 65 years	2 Participants	2 Participants	8 Participants	1 Participants	13 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	4 Participants	3 Participants	11 Participants	4 Participants	22 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	4 Participants	3 Participants	11 Participants	4 Participants	22 Participants
Sex: Female, Male Female	1 Participants	0 Participants	4 Participants	0 Participants	5 Participants
Sex: Female, Male Male	3 Participants	3 Participants	7 Participants	4 Participants	17 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 4	0 / 3	0 / 11	0 / 4
other Total, other adverse events	1 / 4	1 / 3	3 / 11	1 / 4
serious Total, serious adverse events	0 / 4	0 / 3	0 / 11	0 / 4

Outcome results

Primary

Part A: Change in Cardiac Index (CI) Measured by Right Heart Catheterization (RHC) From Baseline to End of Intravenous (IV) Infusion at 6 Hours

Cardiac index (CI) is a hemodynamic parameter that relates the cardiac output (CO) from left ventricle in one minute to body surface area (BSA), thus relating heart performance to the body size of the participant. It was measured by RHC.

Time frame: Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)

Population: Full analysis set included all randomized participants, irrespective of whether they received any study treatment.

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Cardiac Index (CI) Measured by Right Heart Catheterization (RHC) From Baseline to End of Intravenous (IV) Infusion at 6 Hours	0.33 Liter per minute per meter square	Standard Deviation 0.66
Cohort 1- Placebo	Part A: Change in Cardiac Index (CI) Measured by Right Heart Catheterization (RHC) From Baseline to End of Intravenous (IV) Infusion at 6 Hours	0.10 Liter per minute per meter square	Standard Deviation 0.1
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Cardiac Index (CI) Measured by Right Heart Catheterization (RHC) From Baseline to End of Intravenous (IV) Infusion at 6 Hours	0.25 Liter per minute per meter square	Standard Deviation 0.372
Cohort 2- Placebo	Part A: Change in Cardiac Index (CI) Measured by Right Heart Catheterization (RHC) From Baseline to End of Intravenous (IV) Infusion at 6 Hours	0.10 Liter per minute per meter square	Standard Deviation 0.245

Secondary

Part A: Area Under the Plasma Concentration Time Curve From Time Zero to 6 Hours (AUC[0-6]) of APD418

AUC \[0-6\] was reported in this outcome measure.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6 hours post infusion start

Population: Pharmacokinetic (PK) set included all participants in the safety set with at least 1 post-dose PK measurement.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Area Under the Plasma Concentration Time Curve From Time Zero to 6 Hours (AUC[0-6]) of APD418	6620 Hours*nanogram per milliliter	Geometric Coefficient of Variation 68.7
Cohort 1- Placebo	Part A: Area Under the Plasma Concentration Time Curve From Time Zero to 6 Hours (AUC[0-6]) of APD418	5970 Hours*nanogram per milliliter	Geometric Coefficient of Variation 268

Secondary

Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUCLast) of APD418

AUClast was reported in this outcome measure.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start

Population: PK set included all participants in the safety set with at least 1 post-dose PK measurement.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUCLast) of APD418	9410 Hours*nanogram per milliliter	Geometric Coefficient of Variation 84.3
Cohort 1- Placebo	Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUCLast) of APD418	9230 Hours*nanogram per milliliter	Geometric Coefficient of Variation 164

Secondary

Part A: Area Under the Plasma Concentration Time Curve From Time Zero up to Infinity (AUC[0-Infinity]) of APD418

AUC \[0-infinity\] was reported in this outcome measure.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start

Population: PK set included all participants in the safety set with at least 1 post-dose PK measurement. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Area Under the Plasma Concentration Time Curve From Time Zero up to Infinity (AUC[0-Infinity]) of APD418	9660 Hours*nanogram per milliliter	Geometric Coefficient of Variation 87
Cohort 1- Placebo	Part A: Area Under the Plasma Concentration Time Curve From Time Zero up to Infinity (AUC[0-Infinity]) of APD418	13400 Hours*nanogram per milliliter	Geometric Coefficient of Variation 34.5

Secondary

Part A: Average Plasma Concentration During Dosing Interval (Cave) for ADP418

Average plasma concentration calculated over the 6-hour infusion time was reported in this outcome measure.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6 hours post infusion start

Population: PK set included all participants in the safety set with at least 1 post-dose PK measurement.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Average Plasma Concentration During Dosing Interval (Cave) for ADP418	1100 Nanogram per milliliter	Geometric Coefficient of Variation 68.7
Cohort 1- Placebo	Part A: Average Plasma Concentration During Dosing Interval (Cave) for ADP418	996 Nanogram per milliliter	Geometric Coefficient of Variation 268

Secondary

Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours

Change in CO measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 hours during the 6-hour IV infusion was reported in this outcome measure.

Time frame: Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion

Population: Full analysis set included all randomized participants, irrespective of whether they received any study treatment.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	0.5 hours	-0.15 Liter per minute	Standard Deviation 0.42
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	5 hours	0.43 Liter per minute	Standard Deviation 0.911
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	4 hours	0.43 Liter per minute	Standard Deviation 0.222
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	1 hour	0.68 Liter per minute	Standard Deviation 0.457
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	6 hours	0.75 Liter per minute	Standard Deviation 1.42
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	2 hours	0.90 Liter per minute	Standard Deviation 0.876
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	3 hours	1.28 Liter per minute	Standard Deviation 0.877
Cohort 1- Placebo	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	5 hours	0.43 Liter per minute	Standard Deviation 0.379
Cohort 1- Placebo	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	3 hours	0.47 Liter per minute	Standard Deviation 0.643
Cohort 1- Placebo	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	2 hours	0.43 Liter per minute	Standard Deviation 0.231
Cohort 1- Placebo	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	4 hours	0.27 Liter per minute	Standard Deviation 0.231
Cohort 1- Placebo	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	6 hours	0.30 Liter per minute	Standard Deviation 0.346
Cohort 1- Placebo	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	1 hour	0.67 Liter per minute	Standard Deviation 0.907
Cohort 1- Placebo	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	0.5 hours	0.63 Liter per minute	Standard Deviation 0.777
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	3 hours	0.41 Liter per minute	Standard Deviation 0.568
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	0.5 hours	0.20 Liter per minute	Standard Deviation 0.329
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	1 hour	0.15 Liter per minute	Standard Deviation 0.23
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	2 hours	0.21 Liter per minute	Standard Deviation 0.212
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	4 hours	0.18 Liter per minute	Standard Deviation 0.467
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	5 hours	0.25 Liter per minute	Standard Deviation 0.559
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	6 hours	0.53 Liter per minute	Standard Deviation 0.742
Cohort 2- Placebo	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	2 hours	-0.08 Liter per minute	Standard Deviation 0.189
Cohort 2- Placebo	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	6 hours	0.23 Liter per minute	Standard Deviation 0.499
Cohort 2- Placebo	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	5 hours	0.15 Liter per minute	Standard Deviation 0.191
Cohort 2- Placebo	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	1 hour	0.13 Liter per minute	Standard Deviation 0.34
Cohort 2- Placebo	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	0.5 hours	-0.15 Liter per minute	Standard Deviation 0.3
Cohort 2- Placebo	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	4 hours	0.20 Liter per minute	Standard Deviation 0.56
Cohort 2- Placebo	Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	3 hours	0.33 Liter per minute	Standard Deviation 0.299

Secondary

Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion

CI is a hemodynamic parameter that relates the CO from left ventricle in one minute to BSA, thus relating heart performance to the body size of the participant. It was measured by RHC.

Time frame: Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4 and 5 hours of IV infusion

Population: Full analysis set included all randomized participants, irrespective of whether they received any study treatment.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	0.5 hours	-0.05 Liter per minute per meter square	Standard Deviation 0.252
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	5 hours	0.23 Liter per minute per meter square	Standard Deviation 0.457
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	2 hours	0.45 Liter per minute per meter square	Standard Deviation 0.37
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	4 hours	0.25 Liter per minute per meter square	Standard Deviation 0.1
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	3 hours	0.68 Liter per minute per meter square	Standard Deviation 0.427
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	1 hour	0.35 Liter per minute per meter square	Standard Deviation 0.252
Cohort 1- Placebo	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	3 hours	0.20 Liter per minute per meter square	Standard Deviation 0.265
Cohort 1- Placebo	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	4 hours	0.10 Liter per minute per meter square	Standard Deviation 0.1
Cohort 1- Placebo	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	5 hours	0.17 Liter per minute per meter square	Standard Deviation 0.153
Cohort 1- Placebo	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	0.5 hours	0.27 Liter per minute per meter square	Standard Deviation 0.379
Cohort 1- Placebo	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	1 hour	0.27 Liter per minute per meter square	Standard Deviation 0.379
Cohort 1- Placebo	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	2 hours	0.13 Liter per minute per meter square	Standard Deviation 0.058
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	0.5 hours	0.10 Liter per minute per meter square	Standard Deviation 0.167
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	4 hours	0.09 Liter per minute per meter square	Standard Deviation 0.221
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	1 hour	0.06 Liter per minute per meter square	Standard Deviation 0.112
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	3 hours	0.20 Liter per minute per meter square	Standard Deviation 0.279
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	5 hours	0.11 Liter per minute per meter square	Standard Deviation 0.274
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	2 hours	0.11 Liter per minute per meter square	Standard Deviation 0.104
Cohort 2- Placebo	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	1 hour	0.05 Liter per minute per meter square	Standard Deviation 0.208
Cohort 2- Placebo	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	3 hours	0.15 Liter per minute per meter square	Standard Deviation 0.129
Cohort 2- Placebo	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	2 hours	-0.08 Liter per minute per meter square	Standard Deviation 0.126
Cohort 2- Placebo	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	4 hours	0.10 Liter per minute per meter square	Standard Deviation 0.346
Cohort 2- Placebo	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	5 hours	0.08 Liter per minute per meter square	Standard Deviation 0.096
Cohort 2- Placebo	Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion	0.5 hours	-0.10 Liter per minute per meter square	Standard Deviation 0.183

Secondary

Part A: Change in Fractional Shortening (FS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours

FS was calculated by measuring the percentage reduction in left ventricular diameter during systole. This was measured by ECHO.

Time frame: Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)

Population: Full analysis set included all randomized participants, irrespective of whether they received any study treatment.

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Fractional Shortening (FS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	-2.60 Percentage	Standard Deviation 7.791
Cohort 1- Placebo	Part A: Change in Fractional Shortening (FS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	0.47 Percentage	Standard Deviation 5.71
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Fractional Shortening (FS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	-1.55 Percentage	Standard Deviation 1.924
Cohort 2- Placebo	Part A: Change in Fractional Shortening (FS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	-4.50 Percentage	Standard Deviation 7.444

Secondary

Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours

Heart rate was measured in a supine or seated position after participant had at least 5 minutes of rest.

Time frame: Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion

Population: Full analysis set included all randomized participants, irrespective of whether they received any study treatment.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	0.5 hours	-8.8 Beats per minute	Standard Deviation 9
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	5 hours	-6.3 Beats per minute	Standard Deviation 6.08
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	4 hours	-0.5 Beats per minute	Standard Deviation 6.24
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	1 hour	-2.5 Beats per minute	Standard Deviation 2.65
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	6 hours	4.5 Beats per minute	Standard Deviation 9
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	2 hours	-2.3 Beats per minute	Standard Deviation 5.32
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	3 hours	2.0 Beats per minute	Standard Deviation 8.87
Cohort 1- Placebo	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	5 hours	-1.7 Beats per minute	Standard Deviation 5.86
Cohort 1- Placebo	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	3 hours	0.0 Beats per minute	Standard Deviation 9.17
Cohort 1- Placebo	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	2 hours	-0.7 Beats per minute	Standard Deviation 9.07
Cohort 1- Placebo	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	4 hours	0.3 Beats per minute	Standard Deviation 14.22
Cohort 1- Placebo	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	6 hours	1.0 Beats per minute	Standard Deviation 5.57
Cohort 1- Placebo	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	1 hour	-3.3 Beats per minute	Standard Deviation 14.19
Cohort 1- Placebo	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	0.5 hours	-7.3 Beats per minute	Standard Deviation 12.66
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	3 hours	-0.6 Beats per minute	Standard Deviation 8.31
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	0.5 hours	0.0 Beats per minute	Standard Deviation 5.93
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	1 hour	-1.6 Beats per minute	Standard Deviation 4.86
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	2 hours	-1.5 Beats per minute	Standard Deviation 6.62
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	4 hours	-1.1 Beats per minute	Standard Deviation 5.8
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	5 hours	-1.5 Beats per minute	Standard Deviation 5.77
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	6 hours	4.2 Beats per minute	Standard Deviation 9.22
Cohort 2- Placebo	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	2 hours	-7.0 Beats per minute	Standard Deviation 13.49
Cohort 2- Placebo	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	6 hours	-1.5 Beats per minute	Standard Deviation 17.82
Cohort 2- Placebo	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	5 hours	-5.0 Beats per minute	Standard Deviation 13.49
Cohort 2- Placebo	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	1 hour	-9.0 Beats per minute	Standard Deviation 13.29
Cohort 2- Placebo	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	0.5 hours	3.5 Beats per minute	Standard Deviation 9.11
Cohort 2- Placebo	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	4 hours	1.0 Beats per minute	Standard Deviation 20.02
Cohort 2- Placebo	Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours	3 hours	-5.3 Beats per minute	Standard Deviation 11.18

Secondary

Part A: Change in Left Ventricular Ejection Fraction (LVEF) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours

LVEF is the central measure of left ventricular systolic function. LVEF is the fraction of chamber volume ejected in systole (stroke volume) in relation to the volume of the blood in the ventricle at the end of diastole (end-diastolic volume). This was measured by ECHO.

Time frame: Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)

Population: Full analysis set included all randomized participants, irrespective of whether they received any study treatment.

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Left Ventricular Ejection Fraction (LVEF) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	1.90 Percentage of end diastolic volume	Standard Deviation 6.009
Cohort 1- Placebo	Part A: Change in Left Ventricular Ejection Fraction (LVEF) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	0.47 Percentage of end diastolic volume	Standard Deviation 1.457
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Left Ventricular Ejection Fraction (LVEF) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	1.14 Percentage of end diastolic volume	Standard Deviation 3.204
Cohort 2- Placebo	Part A: Change in Left Ventricular Ejection Fraction (LVEF) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	-1.68 Percentage of end diastolic volume	Standard Deviation 0.9

Secondary

Part A: Change in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO From Baseline to End of IV Infusion at 6 Hours

Left ventricular end-systolic diameter and left ventricular end-diastolic diameter were measured using ECHO.

Time frame: Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)

Population: Full analysis set included all randomized participants, irrespective of whether they received any study treatment.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	Left ventricular end-systolic diameter	0.10 Centimeter (cm)	Standard Deviation 0.361
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	Left ventricular end-diastolic diameter	-0.04 Centimeter (cm)	Standard Deviation 0.087
Cohort 1- Placebo	Part A: Change in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	Left ventricular end-diastolic diameter	-0.02 Centimeter (cm)	Standard Deviation 0.098
Cohort 1- Placebo	Part A: Change in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	Left ventricular end-systolic diameter	-0.04 Centimeter (cm)	Standard Deviation 0.384
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	Left ventricular end-systolic diameter	0.22 Centimeter (cm)	Standard Deviation 0.321
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	Left ventricular end-diastolic diameter	0.15 Centimeter (cm)	Standard Deviation 0.363
Cohort 2- Placebo	Part A: Change in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	Left ventricular end-systolic diameter	0.35 Centimeter (cm)	Standard Deviation 0.544
Cohort 2- Placebo	Part A: Change in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	Left ventricular end-diastolic diameter	0.16 Centimeter (cm)	Standard Deviation 0.243

Secondary

Part A: Change in Left Ventricular Global Longitudinal Strain (LVGLS) and Left Ventricular Global Circumferential Strain (LVGCS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours

Left ventricular global strain is the average strain of the cardiac chamber wall, where LVGLS presents longitudinal shortening as a percentage (change in length as a proportion to baseline length). LVGCS measures the chamber deformation along the circumference of the cardiac wall in a tangential xy-direction and similarly presents the circumferential shortening as a percentage. Both the parameters were measured by ECHO.

Time frame: Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)

Population: Full analysis set included all randomized participants, irrespective of whether they received any study treatment. Here, 'Number of Participants Analyzed' signifies number of participants evaluable for this outcome measure and 'Number Analyzed' signifies participants evaluable for the specified rows.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Left Ventricular Global Longitudinal Strain (LVGLS) and Left Ventricular Global Circumferential Strain (LVGCS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	LVGLS	0.30 Percentage	—
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Left Ventricular Global Longitudinal Strain (LVGLS) and Left Ventricular Global Circumferential Strain (LVGCS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	LVGCS	-6.70 Percentage	—
Cohort 1- Placebo	Part A: Change in Left Ventricular Global Longitudinal Strain (LVGLS) and Left Ventricular Global Circumferential Strain (LVGCS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	LVGLS	-1.10 Percentage	—
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Left Ventricular Global Longitudinal Strain (LVGLS) and Left Ventricular Global Circumferential Strain (LVGCS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	LVGCS	0.05 Percentage	Standard Deviation 2.105
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Left Ventricular Global Longitudinal Strain (LVGLS) and Left Ventricular Global Circumferential Strain (LVGCS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	LVGLS	1.10 Percentage	Standard Deviation 1.337
Cohort 2- Placebo	Part A: Change in Left Ventricular Global Longitudinal Strain (LVGLS) and Left Ventricular Global Circumferential Strain (LVGCS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	LVGLS	-1.29 Percentage	Standard Deviation 0.987
Cohort 2- Placebo	Part A: Change in Left Ventricular Global Longitudinal Strain (LVGLS) and Left Ventricular Global Circumferential Strain (LVGCS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	LVGCS	0.00 Percentage	Standard Deviation 3.111

Secondary

Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours

PAPi is a hemodynamic parameter that is derived from right atrial and pulmonary artery pulse pressures. PAPi = (PAS - PAD)/right atrial pressure. Change in PAPi measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 hours during the 6-hour IV infusion was reported in this outcome measure.

Time frame: Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion

Population: Full analysis set included all randomized participants, irrespective of whether they received any study treatment. All participants reported under 'Number of Participants Analyzed' contributed data to the table but may not have evaluable data for every row. Here, 'Number Analyzed' (n) signifies number of participants evaluable for specified timepoints.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 0.5 hours	0.28 Ratio	Standard Deviation 0.411
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 5 hours	0.95 Ratio	Standard Deviation 0.597
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 4 hours	1.35 Ratio	Standard Deviation 1.838
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 1 hour	-0.08 Ratio	Standard Deviation 0.562
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 6 hours	0.93 Ratio	Standard Deviation 0.929
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 2 hours	0.38 Ratio	Standard Deviation 0.435
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 3 hours	0.65 Ratio	Standard Deviation 0.624
Cohort 1- Placebo	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 5 hours	2.33 Ratio	Standard Deviation 1.818
Cohort 1- Placebo	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 3 hours	0.43 Ratio	Standard Deviation 0.777
Cohort 1- Placebo	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 2 hours	0.33 Ratio	Standard Deviation 0.058
Cohort 1- Placebo	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 4 hours	0.83 Ratio	Standard Deviation 1.834
Cohort 1- Placebo	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 6 hours	1.27 Ratio	Standard Deviation 0.929
Cohort 1- Placebo	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 1 hour	0.17 Ratio	Standard Deviation 0.306
Cohort 1- Placebo	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 0.5 hours	-0.17 Ratio	Standard Deviation 0.833
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 3 hours	0.03 Ratio	Standard Deviation 0.897
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 0.5 hours	-0.11 Ratio	Standard Deviation 0.713
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 1 hour	-0.21 Ratio	Standard Deviation 0.835
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 2 hours	-0.14 Ratio	Standard Deviation 1.011
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 4 hours	0.27 Ratio	Standard Deviation 1.203
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 5 hours	-0.01 Ratio	Standard Deviation 0.872
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 6 hours	0.77 Ratio	Standard Deviation 2.47
Cohort 2- Placebo	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 2 hours	0.20 Ratio	Standard Deviation 0.9
Cohort 2- Placebo	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 6 hours	-0.90 Ratio	Standard Deviation 0.173
Cohort 2- Placebo	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 5 hours	0.87 Ratio	Standard Deviation 2.639
Cohort 2- Placebo	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 1 hour	-0.17 Ratio	Standard Deviation 0.603
Cohort 2- Placebo	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 0.5 hours	0.37 Ratio	Standard Deviation 1.343
Cohort 2- Placebo	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 4 hours	-1.03 Ratio	Standard Deviation 0.907
Cohort 2- Placebo	Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAPi: 3 hours	-0.33 Ratio	Standard Deviation 0.611

Secondary

Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours

PCWP estimated the left atrial pressure and was the pressure measured by wedging a pulmonary artery catheter with an inflated balloon into a small pulmonary arterial branch. PCWP was assessed by 2 successive measurements at least 10 minutes apart. RAP is the blood pressure in the right atrium of the heart. Change in PCWP, RAP, PAS/PAD at 0.5, 1, 2, 3, 4, 5 and 6 hours during the 6-hour IV infusion was reported in this outcome measure. All the parameters were measured by RHC.

Time frame: Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 0.5 hours	1.50 Millimeters of mercury	Standard Deviation 2.887
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 5 hours	-2.50 Millimeters of mercury	Standard Deviation 4.041
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 1 hour	4.50 Millimeters of mercury	Standard Deviation 9.147
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 4 hours	-2.75 Millimeters of mercury	Standard Deviation 3.948
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 6 hours	4.25 Millimeters of mercury	Standard Deviation 9.179
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 2 hours	6.25 Millimeters of mercury	Standard Deviation 4.717
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 3 hours	7.25 Millimeters of mercury	Standard Deviation 6.185
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 0.5 hours	1.50 Millimeters of mercury	Standard Deviation 5.196
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 5 hours	6.00 Millimeters of mercury	Standard Deviation 11.195
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 4 hours	5.75 Millimeters of mercury	Standard Deviation 13.525
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 5 hours	-0.50 Millimeters of mercury	Standard Deviation 6.137
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 4 hours	-3.50 Millimeters of mercury	Standard Deviation 8.888
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 6 hours	-0.75 Millimeters of mercury	Standard Deviation 7.411
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 6 hours	-4.00 Millimeters of mercury	Standard Deviation 5.831
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 0.5 hours	0.50 Millimeters of mercury	Standard Deviation 1.291
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 2 hours	-1.50 Millimeters of mercury	Standard Deviation 5
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 3 hours	-1.25 Millimeters of mercury	Standard Deviation 4.193
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 1 hour	2.50 Millimeters of mercury	Standard Deviation 3.317
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 2 hours	1.00 Millimeters of mercury	Standard Deviation 0.816
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 2 hours	-0.25 Millimeters of mercury	Standard Deviation 2.217
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 3 hours	-0.25 Millimeters of mercury	Standard Deviation 1.258
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 4 hours	-0.75 Millimeters of mercury	Standard Deviation 4.5
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 3 hours	-3.75 Millimeters of mercury	Standard Deviation 3.594
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 1 hour	0.50 Millimeters of mercury	Standard Deviation 2.646
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 5 hours	-1.50 Millimeters of mercury	Standard Deviation 3.416
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 6 hours	-0.67 Millimeters of mercury	Standard Deviation 4.041
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 1 hour	-0.25 Millimeters of mercury	Standard Deviation 8.808
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 0.5 hours	-1.25 Millimeters of mercury	Standard Deviation 3.5
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 5 hours	1.00 Millimeters of mercury	Standard Deviation 2.646
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 0.5 hours	-1.00 Millimeters of mercury	Standard Deviation 2.646
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 0.5 hours	0.00 Millimeters of mercury	Standard Deviation 1.732
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 6 hours	2.67 Millimeters of mercury	Standard Deviation 2.309
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 1 hour	-1.33 Millimeters of mercury	Standard Deviation 0.577
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 1 hour	-0.67 Millimeters of mercury	Standard Deviation 4.041
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 5 hours	-2.67 Millimeters of mercury	Standard Deviation 1.155
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 4 hours	-0.67 Millimeters of mercury	Standard Deviation 1.155
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 1 hour	0.33 Millimeters of mercury	Standard Deviation 2.309
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 2 hours	0.67 Millimeters of mercury	Standard Deviation 0.577
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 4 hours	-0.67 Millimeters of mercury	Standard Deviation 5.033
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 5 hours	5.00 Millimeters of mercury	Standard Deviation 1
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 2 hours	-3.33 Millimeters of mercury	Standard Deviation 1.528
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 3 hours	1.67 Millimeters of mercury	Standard Deviation 5.033
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 2 hours	-0.67 Millimeters of mercury	Standard Deviation 2.517
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 3 hours	-0.33 Millimeters of mercury	Standard Deviation 4.509
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 2 hours	-1.00 Millimeters of mercury	Standard Deviation 1
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 4 hours	2.00 Millimeters of mercury	Standard Deviation 4.359
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 1 hour	-2.33 Millimeters of mercury	Standard Deviation 4.041
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 4 hours	1.33 Millimeters of mercury	Standard Deviation 1.155
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 6 hours	1.33 Millimeters of mercury	Standard Deviation 3.215
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 5 hours	-1.33 Millimeters of mercury	Standard Deviation 6.11
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 0.5 hours	0.67 Millimeters of mercury	Standard Deviation 3.055
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 0.5 hours	0.00 Millimeters of mercury	Standard Deviation 0
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 6 hours	-1.67 Millimeters of mercury	Standard Deviation 1.528
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 6 hours	-1.67 Millimeters of mercury	Standard Deviation 5.686
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 3 hours	0.33 Millimeters of mercury	Standard Deviation 2.517
Cohort 1- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 3 hours	1.00 Millimeters of mercury	Standard Deviation 2.646
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 3 hours	-1.40 Millimeters of mercury	Standard Deviation 9.383
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 0.5 hours	-0.78 Millimeters of mercury	Standard Deviation 3.456
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 1 hour	-2.00 Millimeters of mercury	Standard Deviation 2.828
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 2 hours	1.56 Millimeters of mercury	Standard Deviation 3.609
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 3 hours	-3.67 Millimeters of mercury	Standard Deviation 3.464
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 4 hours	-2.90 Millimeters of mercury	Standard Deviation 5.384
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 5 hours	-1.56 Millimeters of mercury	Standard Deviation 2.698
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 6 hours	-1.25 Millimeters of mercury	Standard Deviation 2.315
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 0.5 hours	1.40 Millimeters of mercury	Standard Deviation 3.836
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 1 hour	0.00 Millimeters of mercury	Standard Deviation 2.867
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 2 hours	1.00 Millimeters of mercury	Standard Deviation 4.397
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 3 hours	0.40 Millimeters of mercury	Standard Deviation 2.366
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 4 hours	-0.20 Millimeters of mercury	Standard Deviation 4.315
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 5 hours	0.50 Millimeters of mercury	Standard Deviation 4.301
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 6 hours	-0.50 Millimeters of mercury	Standard Deviation 5.233
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 0.5 hours	0.20 Millimeters of mercury	Standard Deviation 6.033
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 1 hour	-1.50 Millimeters of mercury	Standard Deviation 4.859
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 2 hours	0.90 Millimeters of mercury	Standard Deviation 6.74
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 4 hours	-1.70 Millimeters of mercury	Standard Deviation 6.201
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 5 hours	-1.30 Millimeters of mercury	Standard Deviation 6.945
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 6 hours	-0.90 Millimeters of mercury	Standard Deviation 8.569
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 0.5 hours	-1.00 Millimeters of mercury	Standard Deviation 2.789
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 1 hour	-0.90 Millimeters of mercury	Standard Deviation 3.872
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 2 hours	-0.70 Millimeters of mercury	Standard Deviation 3.86
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 3 hours	-3.60 Millimeters of mercury	Standard Deviation 5.168
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 4 hours	-2.40 Millimeters of mercury	Standard Deviation 4.061
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 5 hours	-2.40 Millimeters of mercury	Standard Deviation 3.688
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 6 hours	-1.80 Millimeters of mercury	Standard Deviation 4.984
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 6 hours	4.00 Millimeters of mercury	Standard Deviation 8.66
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 5 hours	1.67 Millimeters of mercury	Standard Deviation 8.327
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 2 hours	-0.67 Millimeters of mercury	Standard Deviation 7.506
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 0.5 hours	0.33 Millimeters of mercury	Standard Deviation 4.509
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 4 hours	4.00 Millimeters of mercury	Standard Deviation 6.083
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 3 hours	3.33 Millimeters of mercury	Standard Deviation 8.505
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 6 hours	0.67 Millimeters of mercury	Standard Deviation 5.686
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 1 hour	-1.67 Millimeters of mercury	Standard Deviation 4.041
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 2 hours	2.67 Millimeters of mercury	Standard Deviation 7.234
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 1 hour	3.33 Millimeters of mercury	Standard Deviation 6.658
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 5 hours	1.33 Millimeters of mercury	Standard Deviation 5.033
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 2 hours	-1.00 Millimeters of mercury	Standard Deviation 3
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	RAP: 0.5 hours	-1.33 Millimeters of mercury	Standard Deviation 2.517
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 6 hours	-1.67 Millimeters of mercury	Standard Deviation 9.504
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 1 hour	-2.67 Millimeters of mercury	Standard Deviation 8.145
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 3 hours	0.00 Millimeters of mercury	Standard Deviation 6.245
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 5 hours	-3.33 Millimeters of mercury	Standard Deviation 9.018
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 4 hours	-5.00 Millimeters of mercury	Standard Deviation 9.165
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 0.5 hours	-2.67 Millimeters of mercury	Standard Deviation 4.726
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 4 hours	-8.33 Millimeters of mercury	Standard Deviation 15.631
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 3 hours	-3.33 Millimeters of mercury	Standard Deviation 9.292
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 2 hours	0.33 Millimeters of mercury	Standard Deviation 4.933
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAD: 4 hours	-3.00 Millimeters of mercury	Standard Deviation 7.937
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 5 hours	-1.33 Millimeters of mercury	Standard Deviation 6.658
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 1 hour	-0.67 Millimeters of mercury	Standard Deviation 6.028
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 0.5 hours	-0.67 Millimeters of mercury	Standard Deviation 6.11
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PCWP: 3 hours	-3.67 Millimeters of mercury	Standard Deviation 7.506
Cohort 2- Placebo	Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PAS: 6 hours	-4.33 Millimeters of mercury	Standard Deviation 9.609

Secondary

Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours

PVR is the resistance against blood flow from the pulmonary artery to the left atrium. Change in PVR measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 hours during the 6 hour IV infusion was reported in this outcome measure.

Time frame: Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 4 hours	32.28 dynes*second per centimeter^5	Standard Deviation 190.279
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 6 hours	2.70 dynes*second per centimeter^5	Standard Deviation 150.529
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 2 hours	37.68 dynes*second per centimeter^5	Standard Deviation 106.364
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 0.5 hours	-28.98 dynes*second per centimeter^5	Standard Deviation 21.955
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 1 hour	5.80 dynes*second per centimeter^5	Standard Deviation 108.571
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 3 hours	29.70 dynes*second per centimeter^5	Standard Deviation 99.607
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 5 hours	29.08 dynes*second per centimeter^5	Standard Deviation 163.825
Cohort 1- Placebo	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 3 hours	-11.60 dynes*second per centimeter^5	Standard Deviation 69.295
Cohort 1- Placebo	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 4 hours	10.03 dynes*second per centimeter^5	Standard Deviation 72.673
Cohort 1- Placebo	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 6 hours	54.57 dynes*second per centimeter^5	Standard Deviation 15.245
Cohort 1- Placebo	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 1 hour	-37.57 dynes*second per centimeter^5	Standard Deviation 102.284
Cohort 1- Placebo	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 0.5 hours	-97.13 dynes*second per centimeter^5	Standard Deviation 134.474
Cohort 1- Placebo	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 5 hours	44.57 dynes*second per centimeter^5	Standard Deviation 38.099
Cohort 1- Placebo	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 2 hours	46.43 dynes*second per centimeter^5	Standard Deviation 27.918
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 3 hours	36.04 dynes*second per centimeter^5	Standard Deviation 171.091
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 0.5 hours	14.83 dynes*second per centimeter^5	Standard Deviation 115.974
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 1 hour	78.37 dynes*second per centimeter^5	Standard Deviation 235.884
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 2 hours	-1.64 dynes*second per centimeter^5	Standard Deviation 290.121
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 4 hours	32.44 dynes*second per centimeter^5	Standard Deviation 191.341
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 5 hours	22.61 dynes*second per centimeter^5	Standard Deviation 195.626
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 6 hours	38.10 dynes*second per centimeter^5	Standard Deviation 291.188
Cohort 2- Placebo	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 2 hours	-0.10 dynes*second per centimeter^5	Standard Deviation 136.989
Cohort 2- Placebo	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 6 hours	19.53 dynes*second per centimeter^5	Standard Deviation 86.649
Cohort 2- Placebo	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 5 hours	53.70 dynes*second per centimeter^5	Standard Deviation 211.59
Cohort 2- Placebo	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 1 hour	6.40 dynes*second per centimeter^5	Standard Deviation 115.783
Cohort 2- Placebo	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 0.5 hours	83.40 dynes*second per centimeter^5	Standard Deviation 80.442
Cohort 2- Placebo	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 4 hours	-44.03 dynes*second per centimeter^5	Standard Deviation 121.31
Cohort 2- Placebo	Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	PVR: 3 hours	18.13 dynes*second per centimeter^5	Standard Deviation 107.316

Secondary

Part A: Change in Stroke Volume Index (SVI) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours

SVI was calculated as stroke volume divided by BSA. This was measured by ECHO.

Time frame: Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Stroke Volume Index (SVI) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	1.50 Milliliter per meter square	Standard Deviation 5.518
Cohort 1- Placebo	Part A: Change in Stroke Volume Index (SVI) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	-0.30 Milliliter per meter square	—
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Stroke Volume Index (SVI) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	2.62 Milliliter per meter square	Standard Deviation 4.615
Cohort 2- Placebo	Part A: Change in Stroke Volume Index (SVI) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours	-2.00 Milliliter per meter square	Standard Deviation 4.492

Secondary

Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours

SV is the volume of blood pumped from the left ventricle per beat. LVESV is the volume of blood in the left ventricle at the end of contraction and at diastole. LVEDV is the amount of blood in the heart's left ventricle just before the heart contracts. All these parameters were measured by ECHO.

Time frame: Baseline (within 2 hours prior to start of study treatment administration) up to 6 Hours (end of IV infusion)

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours	Stroke Volume	3.13 Milliliter	Standard Deviation 10.623
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours	LVEDV	-7.92 Milliliter	Standard Deviation 15.531
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours	LVESV	-11.05 Milliliter	Standard Deviation 22.837
Cohort 1- Placebo	Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours	Stroke Volume	-0.80 Milliliter	—
Cohort 1- Placebo	Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours	LVEDV	3.30 Milliliter	—
Cohort 1- Placebo	Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours	LVESV	4.10 Milliliter	—
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours	LVESV	8.28 Milliliter	Standard Deviation 25.689
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours	Stroke Volume	5.94 Milliliter	Standard Deviation 10.183
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours	LVEDV	14.20 Milliliter	Standard Deviation 31.021
Cohort 2- Placebo	Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours	Stroke Volume	-3.15 Milliliter	Standard Deviation 7.152
Cohort 2- Placebo	Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours	LVEDV	7.30 Milliliter	Standard Deviation 38.006
Cohort 2- Placebo	Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours	LVESV	8.92 Milliliter	Standard Deviation 29.804

Secondary

Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours

SVRI was calculated by dividing the difference between mean arterial pressure and central venous pressure by cardiac index and multiplying by 80. Change in SVRI measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 hours during the 6 hour IV infusion was reported in this outcome measure.

Time frame: Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 5 hours	12.80 Dynessecondmeter^2 per centimeter^5	Standard Deviation 208.554
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 0.5 hours	5.00 Dynessecondmeter^2 per centimeter^5	Standard Deviation 157.514
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 6 hours	61.47 Dynessecondmeter^2 per centimeter^5	Standard Deviation 205.227
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 2 hours	-115.13 Dynessecondmeter^2 per centimeter^5	Standard Deviation 165.795
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 4 hours	-85.05 Dynessecondmeter^2 per centimeter^5	Standard Deviation 224.198
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 3 hours	-152.98 Dynessecondmeter^2 per centimeter^5	Standard Deviation 108.934
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 1 hour	-156.58 Dynessecondmeter^2 per centimeter^5	Standard Deviation 105.011
Cohort 1- Placebo	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 3 hours	-42.57 Dynessecondmeter^2 per centimeter^5	Standard Deviation 192.932
Cohort 1- Placebo	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 4 hours	201.20 Dynessecondmeter^2 per centimeter^5	Standard Deviation 357.587
Cohort 1- Placebo	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 6 hours	152.63 Dynessecondmeter^2 per centimeter^5	Standard Deviation 171.695
Cohort 1- Placebo	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 1 hour	-202.73 Dynessecondmeter^2 per centimeter^5	Standard Deviation 185.527
Cohort 1- Placebo	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 0.5 hours	-171.20 Dynessecondmeter^2 per centimeter^5	Standard Deviation 154.962
Cohort 1- Placebo	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 5 hours	350.47 Dynessecondmeter^2 per centimeter^5	Standard Deviation 458.646
Cohort 1- Placebo	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 2 hours	-85.30 Dynessecondmeter^2 per centimeter^5	Standard Deviation 63.286
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 3 hours	-190.53 Dynessecondmeter^2 per centimeter^5	Standard Deviation 315.5
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 2 hours	-94.82 Dynessecondmeter^2 per centimeter^5	Standard Deviation 407.893
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 0.5 hours	-98.41 Dynessecondmeter^2 per centimeter^5	Standard Deviation 270.327
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 1 hour	16.20 Dynessecondmeter^2 per centimeter^5	Standard Deviation 404.144
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 4 hours	-31.66 Dynessecondmeter^2 per centimeter^5	Standard Deviation 414.786
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 5 hours	-172.77 Dynessecondmeter^2 per centimeter^5	Standard Deviation 186.678
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 6 hours	-94.08 Dynessecondmeter^2 per centimeter^5	Standard Deviation 306.599
Cohort 2- Placebo	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 2 hours	-64.77 Dynessecondmeter^2 per centimeter^5	Standard Deviation 281.682
Cohort 2- Placebo	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 6 hours	-227.17 Dynessecondmeter^2 per centimeter^5	Standard Deviation 126.337
Cohort 2- Placebo	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 5 hours	-260.83 Dynessecondmeter^2 per centimeter^5	Standard Deviation 484.601
Cohort 2- Placebo	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 1 hour	-289.57 Dynessecondmeter^2 per centimeter^5	Standard Deviation 102.838
Cohort 2- Placebo	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 0.5 hours	107.83 Dynessecondmeter^2 per centimeter^5	Standard Deviation 428.022
Cohort 2- Placebo	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 4 hours	-649.80 Dynessecondmeter^2 per centimeter^5	Standard Deviation 360.988
Cohort 2- Placebo	Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVRI: 3 hours	-403.47 Dynessecondmeter^2 per centimeter^5	Standard Deviation 271.919

Secondary

Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours

Systemic vascular resistance (SVR) is the amount of force exerted on circulating blood by the vasculature of the body. SVR was calculated as 80\*(mean arterial pressure - mean venous pressure) divided by cardiac output. Change in SVR measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 hours during the 6-hour IV infusion was reported in this outcome measure.

Time frame: Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 0.5 hours	10.30 Millimeter of mercury*minutes/milliliter	Standard Deviation 74.776
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 5 hours	21.10 Millimeter of mercury*minutes/milliliter	Standard Deviation 112.824
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 4 hours	-27.20 Millimeter of mercury*minutes/milliliter	Standard Deviation 104.351
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 1 hour	-80.50 Millimeter of mercury*minutes/milliliter	Standard Deviation 57.295
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 6 hours	33.10 Millimeter of mercury*minutes/milliliter	Standard Deviation 106.652
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 2 hours	-48.83 Millimeter of mercury*minutes/milliliter	Standard Deviation 71.811
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 3 hours	-67.63 Millimeter of mercury*minutes/milliliter	Standard Deviation 56.169
Cohort 1- Placebo	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 5 hours	132.63 Millimeter of mercury*minutes/milliliter	Standard Deviation 171.63
Cohort 1- Placebo	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 3 hours	-8.10 Millimeter of mercury*minutes/milliliter	Standard Deviation 102.327
Cohort 1- Placebo	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 2 hours	-46.23 Millimeter of mercury*minutes/milliliter	Standard Deviation 28.762
Cohort 1- Placebo	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 4 hours	73.90 Millimeter of mercury*minutes/milliliter	Standard Deviation 136.245
Cohort 1- Placebo	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 6 hours	90.37 Millimeter of mercury*minutes/milliliter	Standard Deviation 137.576
Cohort 1- Placebo	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 1 hour	-86.30 Millimeter of mercury*minutes/milliliter	Standard Deviation 80.694
Cohort 1- Placebo	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 0.5 hours	-71.27 Millimeter of mercury*minutes/milliliter	Standard Deviation 55.492
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 3 hours	-101.20 Millimeter of mercury*minutes/milliliter	Standard Deviation 188.863
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 0.5 hours	-47.30 Millimeter of mercury*minutes/milliliter	Standard Deviation 139.874
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 1 hour	16.71 Millimeter of mercury*minutes/milliliter	Standard Deviation 231.657
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 2 hours	-42.16 Millimeter of mercury*minutes/milliliter	Standard Deviation 205.772
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 4 hours	-33.91 Millimeter of mercury*minutes/milliliter	Standard Deviation 241.04
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 5 hours	-92.29 Millimeter of mercury*minutes/milliliter	Standard Deviation 94.834
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 6 hours	-70.00 Millimeter of mercury*minutes/milliliter	Standard Deviation 116.681
Cohort 2- Placebo	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 2 hours	-49.40 Millimeter of mercury*minutes/milliliter	Standard Deviation 136.124
Cohort 2- Placebo	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 6 hours	-104.23 Millimeter of mercury*minutes/milliliter	Standard Deviation 90.537
Cohort 2- Placebo	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 5 hours	-110.57 Millimeter of mercury*minutes/milliliter	Standard Deviation 222.498
Cohort 2- Placebo	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 1 hour	-131.93 Millimeter of mercury*minutes/milliliter	Standard Deviation 91.886
Cohort 2- Placebo	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 0.5 hours	74.13 Millimeter of mercury*minutes/milliliter	Standard Deviation 198.427
Cohort 2- Placebo	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 4 hours	-311.03 Millimeter of mercury*minutes/milliliter	Standard Deviation 145.094
Cohort 2- Placebo	Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SVR: 3 hours	-195.77 Millimeter of mercury*minutes/milliliter	Standard Deviation 101.041

Secondary

Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours

SBP, DBP and MAP were measured in a supine or seated position after participant had at least 5 minutes of rest. MAP is the average pressure of the blood circulating through a participant's arteries during the cardiac cycle. MAP was derived by using the following formula: DBP + 1/3(SBP-DBP).

Time frame: Baseline (within 2 hours prior to start of study treatment administration), 0.5, 1, 2, 3, 4, 5 and 6 hours of IV infusion

Population: Full analysis set included all randomized participants, irrespective of whether they received any study treatment.

Arm	Measure	Group	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 2 hours	9.33 Millimeters of mercury	Standard Deviation 13.891
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 5 hours	-0.8 Millimeters of mercury	Standard Deviation 13.67
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 3 hours	-1.0 Millimeters of mercury	Standard Deviation 14.07
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 1 hour	4.25 Millimeters of mercury	Standard Deviation 12.971
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 6 hours	1.3 Millimeters of mercury	Standard Deviation 13.57
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 0.5 hours	7.3 Millimeters of mercury	Standard Deviation 10.21
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 0.5 hours	4.42 Millimeters of mercury	Standard Deviation 13.723
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 1 hour	6.8 Millimeters of mercury	Standard Deviation 10.56
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 5 hours	1.33 Millimeters of mercury	Standard Deviation 13.57
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 4 hours	2.5 Millimeters of mercury	Standard Deviation 15.11
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 6 hours	9.8 Millimeters of mercury	Standard Deviation 12.45
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 4 hours	-1.00 Millimeters of mercury	Standard Deviation 13.101
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 0.5 hours	3.0 Millimeters of mercury	Standard Deviation 16.06
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 6 hours	4.08 Millimeters of mercury	Standard Deviation 12.9
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 1 hour	3.0 Millimeters of mercury	Standard Deviation 14.85
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 2 hours	8.0 Millimeters of mercury	Standard Deviation 14.54
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 3 hours	-3.00 Millimeters of mercury	Standard Deviation 12.64
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 2 hours	10.0 Millimeters of mercury	Standard Deviation 16.12
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 3 hours	-4.0 Millimeters of mercury	Standard Deviation 12.46
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 4 hours	-2.8 Millimeters of mercury	Standard Deviation 13.1
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 2 hours	-6.78 Millimeters of mercury	Standard Deviation 4.623
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 4 hours	0.3 Millimeters of mercury	Standard Deviation 7.77
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 5 hours	-1.00 Millimeters of mercury	Standard Deviation 5.196
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 1 hour	-5.11 Millimeters of mercury	Standard Deviation 3.097
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 6 hours	-5.0 Millimeters of mercury	Standard Deviation 6
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 5 hours	-2.0 Millimeters of mercury	Standard Deviation 1.73
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 0.5 hours	-11.0 Millimeters of mercury	Standard Deviation 10.15
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 6 hours	-0.78 Millimeters of mercury	Standard Deviation 1.388
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 3 hours	-3.3 Millimeters of mercury	Standard Deviation 5.13
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 6 hours	1.3 Millimeters of mercury	Standard Deviation 2.08
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 0.5 hours	-6.7 Millimeters of mercury	Standard Deviation 7.02
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 0.5 hours	-8.11 Millimeters of mercury	Standard Deviation 8.002
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 2 hours	-7.0 Millimeters of mercury	Standard Deviation 2.65
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 3 hours	-4.7 Millimeters of mercury	Standard Deviation 7.77
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 3 hours	-3.78 Millimeters of mercury	Standard Deviation 5.274
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 2 hours	-6.3 Millimeters of mercury	Standard Deviation 9.81
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 1 hour	-4.0 Millimeters of mercury	Standard Deviation 5.29
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 4 hours	-2.7 Millimeters of mercury	Standard Deviation 8.33
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 1 hour	-7.3 Millimeters of mercury	Standard Deviation 1.53
Cohort 1- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 4 hours	-0.67 Millimeters of mercury	Standard Deviation 6.96
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 6 hours	-0.3 Millimeters of mercury	Standard Deviation 6.87
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 0.5 hours	-2.2 Millimeters of mercury	Standard Deviation 11.47
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 1 hour	-3.8 Millimeters of mercury	Standard Deviation 9.44
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 2 hours	-2.6 Millimeters of mercury	Standard Deviation 11.21
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 3 hours	-3.9 Millimeters of mercury	Standard Deviation 10.35
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 4 hours	-3.9 Millimeters of mercury	Standard Deviation 9.66
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 6 hours	-1.4 Millimeters of mercury	Standard Deviation 8.9
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 0.5 hours	-0.2 Millimeters of mercury	Standard Deviation 4.92
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 1 hour	-2.2 Millimeters of mercury	Standard Deviation 5.74
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 2 hours	0.0 Millimeters of mercury	Standard Deviation 7.92
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 3 hours	-4.8 Millimeters of mercury	Standard Deviation 9.26
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 4 hours	-6.3 Millimeters of mercury	Standard Deviation 5.76
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 5 hours	-6.8 Millimeters of mercury	Standard Deviation 6.52
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 0.5 hours	-0.85 Millimeters of mercury	Standard Deviation 4.994
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 1 hour	-2.73 Millimeters of mercury	Standard Deviation 4.718
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 2 hours	-0.88 Millimeters of mercury	Standard Deviation 6.634
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 3 hours	-4.52 Millimeters of mercury	Standard Deviation 7.752
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 4 hours	-5.48 Millimeters of mercury	Standard Deviation 5.768
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 5 hours	-7.30 Millimeters of mercury	Standard Deviation 5.742
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 6 hours	-0.64 Millimeters of mercury	Standard Deviation 5.934
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 3 hours	-1.0 Millimeters of mercury	Standard Deviation 7.79
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 2 hours	-1.5 Millimeters of mercury	Standard Deviation 5.92
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 5 hours	-0.17 Millimeters of mercury	Standard Deviation 7.466
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 2 hours	-0.83 Millimeters of mercury	Standard Deviation 5.828
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 1 hour	7.0 Millimeters of mercury	Standard Deviation 18.2
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 0.5 hours	0.0 Millimeters of mercury	Standard Deviation 4.24
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 1 hour	-0.8 Millimeters of mercury	Standard Deviation 6.18
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 3 hours	-1.00 Millimeters of mercury	Standard Deviation 8.551
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 6 hours	-1.0 Millimeters of mercury	Standard Deviation 12.57
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 4 hours	0.5 Millimeters of mercury	Standard Deviation 14.93
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 0.5 hours	-0.5 Millimeters of mercury	Standard Deviation 6.35
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 4 hours	-0.50 Millimeters of mercury	Standard Deviation 8.131
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 3 hours	-1.0 Millimeters of mercury	Standard Deviation 10.3
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 6 hours	3.8 Millimeters of mercury	Standard Deviation 7.93
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	SBP: 2 hours	0.5 Millimeters of mercury	Standard Deviation 6.14
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 0.5 hours	-0.17 Millimeters of mercury	Standard Deviation 4.041
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 5 hours	-1.0 Millimeters of mercury	Standard Deviation 6.98
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	DBP: 4 hours	-1.0 Millimeters of mercury	Standard Deviation 5.72
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 6 hours	2.17 Millimeters of mercury	Standard Deviation 9.406
Cohort 2- Placebo	Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours	MAP: 1 hour	4.42 Millimeters of mercury	Standard Deviation 10.651

Secondary

Part A: Distributional Half-Life (t1/2a) for APD418

Distributional t1/2 of APD418 was reported in this outcome measure.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Distributional Half-Life (t1/2a) for APD418	0.579 Hours	Standard Deviation 0.381
Cohort 1- Placebo	Part A: Distributional Half-Life (t1/2a) for APD418	0.381 Hours	Standard Deviation 0.119

Secondary

Part A: Maximum Observed Plasma Concentration (Cmax) of APD418

Cmax of APD418 was reported in this outcome measure.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start

Population: PK set included all participants in the safety set with at least 1 post-dose PK measurement.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Maximum Observed Plasma Concentration (Cmax) of APD418	1540 Nanogram per milliliter	Geometric Coefficient of Variation 88.8
Cohort 1- Placebo	Part A: Maximum Observed Plasma Concentration (Cmax) of APD418	1480 Nanogram per milliliter	Geometric Coefficient of Variation 277

Secondary

Part A: Mean Residence Time From Time Zero to Time of Last Quantifiable Plasma Concentration (MRTlast) for APD418

MRTlast of APD418 was reported in this outcome measure.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start

Population: PK set included all participants in the safety set with at least 1 post-dose PK measurement.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Mean Residence Time From Time Zero to Time of Last Quantifiable Plasma Concentration (MRTlast) for APD418	2.44 Hours	Geometric Coefficient of Variation 33.6
Cohort 1- Placebo	Part A: Mean Residence Time From Time Zero to Time of Last Quantifiable Plasma Concentration (MRTlast) for APD418	2.54 Hours	Geometric Coefficient of Variation 74.3

Secondary

Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An AE was any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. TEAEs were defined as those AEs with onset after start date/timepoint of study drug administration.

Time frame: From start of study treatment on Day 1 up to Day 9

Population: Safety set included all randomized participants who received at least one dose of study treatment.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	1 Participants
Cohort 1- Placebo	Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	1 Participants
Cohort 2- 0.5 mg/kg/hr APD418	Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	3 Participants
Cohort 2- Placebo	Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	1 Participants

Secondary

Part A: Renal Clearance (CLr) for ADP418

CLr for APD418 was reported in this outcome measure.

Time frame: Pre-dose (0) to 24 hours post infusion start, collected over 0 to 6 hour, 6 to 10 hour and 10 to 24-hour intervals

Population: PK set included all participants in the safety set with at least 1 post-dose PK measurement.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Renal Clearance (CLr) for ADP418	2.14 Liter per hour	Geometric Coefficient of Variation 55.3
Cohort 1- Placebo	Part A: Renal Clearance (CLr) for ADP418	3.78 Liter per hour	Geometric Coefficient of Variation 54.8

Secondary

Part A: Terminal Elimination Half-Life (t1/2) for APD418

Terminal t1/2 of APD418 was reported in this outcome measure.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start

Arm	Measure	Value (MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Terminal Elimination Half-Life (t1/2) for APD418	5.26 Hours	Standard Deviation 0.96
Cohort 1- Placebo	Part A: Terminal Elimination Half-Life (t1/2) for APD418	5.26 Hours	Standard Deviation 0.998

Secondary

Part A: Time to Maximum Observed Plasma Concentration (Tmax) for APD418

Tmax of APD418 was reported in this outcome measure.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start

Population: PK set included all participants in the safety set with at least 1 post-dose PK measurement.

Arm	Measure	Value (MEDIAN)
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Time to Maximum Observed Plasma Concentration (Tmax) for APD418	5.42 Hours
Cohort 1- Placebo	Part A: Time to Maximum Observed Plasma Concentration (Tmax) for APD418	5.00 Hours

Secondary

Part A: Total Clearance (CL) for APD418

IV CL of APD418 was reported in this outcome measure.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start

Population: The PK set included all participants in the safety set with at least 1 post-dose PK measurement. Here, Number of Participants Analyzed signifies participants evaluable for this outcome measure.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Total Clearance (CL) for APD418	9.16 Liter per hour	Geometric Coefficient of Variation 92.7
Cohort 1- Placebo	Part A: Total Clearance (CL) for APD418	17.8 Liter per hour	Geometric Coefficient of Variation 23.2

Secondary

Part A: Total Volume of Distribution Based on the Terminal Phase (Vdz) for APD418

Vdz of APD418 was reported in this outcome measure.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Total Volume of Distribution Based on the Terminal Phase (Vdz) for APD418	68.6 Liter	Geometric Coefficient of Variation 74.5
Cohort 1- Placebo	Part A: Total Volume of Distribution Based on the Terminal Phase (Vdz) for APD418	133 Liter	Geometric Coefficient of Variation 28.6

Secondary

Part A: Volume of Distribution at Steady State (Vdss) for APD418

Vdss of APD418 was reported in this outcome measure.

Time frame: Pre-dose, 0.5, 1, 2, 3, 4, 5, 6, 6.083, 6.167, 6.25, 6.5, 7, 8, 10, 18 and 24 hours post infusion start

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Volume of Distribution at Steady State (Vdss) for APD418	27.7 Liter	Geometric Coefficient of Variation 42.2
Cohort 1- Placebo	Part A: Volume of Distribution at Steady State (Vdss) for APD418	46.0 Liter	Geometric Coefficient of Variation 34.5

Other Pre-specified

Part A: Amount of Unchanged Drug Excreted in Urine During Each Collection Interval From t1 to t2 (Aet1-t2)

Amount of unchanged drug excreted in urine during each collection interval from t1 to t2 was reported in this outcome measure.

Time frame: Anytime between 0 to 6 hours, 6 to 10 hours and 10 to 24 hours post infusion start

Population: PK set included all participants in the safety set with at least 1 post-dose PK measurement.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Amount of Unchanged Drug Excreted in Urine During Each Collection Interval From t1 to t2 (Aet1-t2)	Ae 0-6	11.8 Milligrams	Geometric Coefficient of Variation 26.7
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Amount of Unchanged Drug Excreted in Urine During Each Collection Interval From t1 to t2 (Aet1-t2)	Ae 6-10	4.47 Milligrams	Geometric Coefficient of Variation 27.3
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Amount of Unchanged Drug Excreted in Urine During Each Collection Interval From t1 to t2 (Aet1-t2)	Ae 10-24	2.83 Milligrams	Geometric Coefficient of Variation 136
Cohort 1- Placebo	Part A: Amount of Unchanged Drug Excreted in Urine During Each Collection Interval From t1 to t2 (Aet1-t2)	Ae 0-6	25.6 Milligrams	Geometric Coefficient of Variation 56.9
Cohort 1- Placebo	Part A: Amount of Unchanged Drug Excreted in Urine During Each Collection Interval From t1 to t2 (Aet1-t2)	Ae 6-10	7.68 Milligrams	Geometric Coefficient of Variation 68.4
Cohort 1- Placebo	Part A: Amount of Unchanged Drug Excreted in Urine During Each Collection Interval From t1 to t2 (Aet1-t2)	Ae 10-24	7.93 Milligrams	Geometric Coefficient of Variation 172

Other Pre-specified

Part A: Fraction of Drug Excreted Unchanged (Fe) in Urine

Fraction of drug excreted in urine was reported in this outcome measure. Data is presented in terms of percentages.

Time frame: Pre-dose (0) to 24 hours post infusion start, collected over 0 to 6 hour, 6 to 10 hour and 10 to 24-hour intervals

Population: PK set included all participants in the safety set with at least 1 post-dose PK measurement.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Fraction of Drug Excreted Unchanged (Fe) in Urine	22.7 Percentage of unchanged drug	Geometric Coefficient of Variation 31.2
Cohort 1- Placebo	Part A: Fraction of Drug Excreted Unchanged (Fe) in Urine	19.7 Percentage of unchanged drug	Geometric Coefficient of Variation 39.8

Other Pre-specified

Part A: Total Amount of Unchanged Drug Excreted in Urine Over the Collection Period (Amount Excreted [Ae])

Total amount of unchanged drug excreted in urine over the collection period was reported in this outcome measure.

Time frame: Pre-dose (0) to 24 hours post infusion start, collected over 0 to 6 hour, 6 to 10 hour and 10 to 24-hour intervals

Population: PK set included all participants in the safety set with at least 1 post-dose PK measurement.

Arm	Measure	Value (GEOMETRIC_MEAN)	Dispersion
Cohort 1- 0.17 mg/kg/hr APD418	Part A: Total Amount of Unchanged Drug Excreted in Urine Over the Collection Period (Amount Excreted [Ae])	20.1 Milligrams	Geometric Coefficient of Variation 28.8
Cohort 1- Placebo	Part A: Total Amount of Unchanged Drug Excreted in Urine Over the Collection Period (Amount Excreted [Ae])	48.5 Milligrams	Geometric Coefficient of Variation 38

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

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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Outcome results

Part A: Change in Cardiac Index (CI) Measured by Right Heart Catheterization (RHC) From Baseline to End of Intravenous (IV) Infusion at 6 Hours

Part A: Area Under the Plasma Concentration Time Curve From Time Zero to 6 Hours (AUC[0-6]) of APD418

Part A: Area Under the Plasma Concentration Time Curve From Time Zero to Last Quantifiable Plasma Concentration (AUCLast) of APD418

Part A: Area Under the Plasma Concentration Time Curve From Time Zero up to Infinity (AUC[0-Infinity]) of APD418

Part A: Average Plasma Concentration During Dosing Interval (Cave) for ADP418

Part A: Change in Cardiac Output (CO) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours

Part A: Change in CI Measured by RHC at 0.5, 1, 2, 3, 4 and 5 Hours During 6 Hour IV Infusion

Part A: Change in Fractional Shortening (FS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours

Part A: Change in Heart Rate at 0.5, 1, 2, 3, 4, 5 and 6 Hours

Part A: Change in Left Ventricular Ejection Fraction (LVEF) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours

Part A: Change in Left Ventricular End-Systolic and Left Ventricular End-Diastolic Diameter Measured by ECHO From Baseline to End of IV Infusion at 6 Hours

Part A: Change in Left Ventricular Global Longitudinal Strain (LVGLS) and Left Ventricular Global Circumferential Strain (LVGCS) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours

Part A: Change in Pulmonary Artery Pulsatility Index (PAPi) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours

Part A: Change in Pulmonary Capillary Wedge Pressure (PCWP), Right Atrial Pressure (RAP), Systolic Pulmonary Arterial Pressure/Diastolic Pulmonary Arterial Pressure (PAS/PAD) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours

Part A: Change in Pulmonary Vascular Resistance (PVR) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours

Part A: Change in Stroke Volume Index (SVI) Measured by ECHO From Baseline to End of IV Infusion at 6 Hours

Part A: Change in Stroke Volume (SV), Left Ventricular End-Systolic Volume (LVESV) and Left Ventricular End-Diastolic Volume (LVEDV) Measured by Echocardiogram (ECHO) From Baseline to End of IV Infusion at 6 Hours

Part A: Change in Systemic Vascular Resistance Index (SVRI) Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours

Part A: Change in Systemic Vascular Resistance Measured by RHC at 0.5, 1, 2, 3, 4, 5 and 6 Hours

Part A: Change in Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP) and Mean Arterial Pressure (MAP) at 0.5, 1, 2, 3, 4, 5 and 6 Hours

Part A: Distributional Half-Life (t1/2a) for APD418

Part A: Maximum Observed Plasma Concentration (Cmax) of APD418

Part A: Mean Residence Time From Time Zero to Time of Last Quantifiable Plasma Concentration (MRTlast) for APD418

Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

Part A: Renal Clearance (CLr) for ADP418

Part A: Terminal Elimination Half-Life (t1/2) for APD418

Part A: Time to Maximum Observed Plasma Concentration (Tmax) for APD418

Part A: Total Clearance (CL) for APD418

Part A: Total Volume of Distribution Based on the Terminal Phase (Vdz) for APD418

Part A: Volume of Distribution at Steady State (Vdss) for APD418

Part A: Amount of Unchanged Drug Excreted in Urine During Each Collection Interval From t1 to t2 (Aet1-t2)

Part A: Fraction of Drug Excreted Unchanged (Fe) in Urine

Part A: Total Amount of Unchanged Drug Excreted in Urine Over the Collection Period (Amount Excreted [Ae])