Trial Outcomes & Findings for Study to Evaluate the Safety and Tolerability of AMG 986 in Healthy Volunteers and Heart Failure Patients (NCT NCT03276728)

Last Updated: 2022-08-08

Results Overview

An adverse event is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment. Events categorized as TEAEs started on or after first dose of study drug and include up to 30 days after the last dose. A serious AE is an AE that met one or more of the following criteria: * Death * Life-threatening * Required inpatient hospitalization or prolongation of an existing hospitalization * Resulted in persistent or significant disability/incapacity * A congenital anomaly/birth defect * Important medical events that required medical or surgical intervention to prevent one of the outcomes above.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

182 participants

Primary outcome timeframe

Part A: Day 1 up to Day 31 Part B: Day 1 up to Day 37 Part C: Day 1 up to Day 51

Results posted on

2022-08-08

Participant Flow

Participants were enrolled at 13 study centers in 7 countries (Canada, France, New Zealand, Netherland, Poland, Singapore, United States). The study included Parts A, B (healthy volunteers) and C (participants with either heart failure with reduced ejection fraction \[HFrEF\] or heart failure with preserved ejection fraction \[HFpEF\]). Each part of the study consisted of ascending dose cohorts.

Within each dose cohort participants were randomized to AMG 986 or placebo in a 3:1 ratio. At the conclusion of each cohort, safety and tolerability of AMG 986 was reviewed before advancing to the next dose cohort. The Statistical Analysis Plan for this study specified that AMG 986 and Placebo-treated participants in Part A and Part B would be combined to form pooled AMG 986 and placebo groups, respectively for each Part.

Participant milestones

Participant milestones
Measure	Part A: Placebo Pooled Healthy participants were administered placebo either intravenously (IV) or by mouth (PO) to match the 5 IV cohorts and 6 PO cohorts of AMG 986.	Part A: AMG 986 Pooled Healthy participants were administered a single dose of AMG 986 either IV or PO. The 5 IV cohorts started at a 0.5 mg loading dose over one hour up to the Cohort 5 IV dosage of a 60 mg loading dose over 1 hour and a 360 mg maintenance dose lasting 23 hours. The 6 PO cohorts started at a single 5 mg dose up to the Cohort 6 PO dose of 650 mg.	Part B: Placebo Pooled Healthy participants were administered placebo either IV for 4 consecutive days or PO for 7 days to match the 2 IV cohorts and 6 PO cohorts of AMG 986.	Part B: AMG 986 Pooled Healthy participants were administered AMG 986 either IV or PO. IV cohort 1 was administered a loading dose of 6 mg over one hour followed by maintenance doses of 36 mg lasting 23 hours on day 1 and 38 mg lasting 24 hours on days 2-4. IV cohort 2 was administered a loading dose of 60 mg lasting one hour followed by maintenance doses of 360 mg lasting 23 hours on day 1 and 376 mg lasting 24 hours on days 2-4. The 6 PO cohorts started at 5 mg for 7 days up to Cohort 6 PO dose of 650 mg for 7 days.	Part C: HFrEF Placebo Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from days 1-21.	Part C: HFpEF Placebo Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO placebo tablet daily from days 1-21.	Part C: HFrEF AMG 986 Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.	Part C: HFpEF AMG 986 Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.
Overall Study STARTED	22	66	16	50	7	1	17	3
Overall Study Treated Participants	22	66	16	50	7	1	16	3
Overall Study COMPLETED	22	66	14	45	6	1	15	2
Overall Study NOT COMPLETED	0	0	2	5	1	0	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Part B: Placebo Pooled Healthy participants were administered placebo either IV for 4 consecutive days or PO for 7 days to match the 2 IV cohorts and 6 PO cohorts of AMG 986.	Part B: AMG 986 Pooled Healthy participants were administered AMG 986 either IV or PO. IV cohort 1 was administered a loading dose of 6 mg over one hour followed by maintenance doses of 36 mg lasting 23 hours on day 1 and 38 mg lasting 24 hours on days 2-4. IV cohort 2 was administered a loading dose of 60 mg lasting one hour followed by maintenance doses of 360 mg lasting 23 hours on day 1 and 376 mg lasting 24 hours on days 2-4. The 6 PO cohorts started at 5 mg for 7 days up to Cohort 6 PO dose of 650 mg for 7 days.	Part C: HFrEF Placebo Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from days 1-21.	Part C: HFrEF AMG 986 Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.	Part C: HFpEF AMG 986 Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.
Overall Study Lost to Follow-up	2	2	0	0	0
Overall Study Withdrawal by Subject	0	3	0	0	0
Overall Study Decision by sponsor	0	0	1	2	1

Baseline Characteristics

Study to Evaluate the Safety and Tolerability of AMG 986 in Healthy Volunteers and Heart Failure Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: Placebo Pooled n=22 Participants Healthy participants were administered placebo either intravenously (IV) or by mouth (PO) to match the 5 IV cohorts and 6 PO cohorts of AMG 986.	Part A: AMG 986 Pooled n=66 Participants Healthy participants were administered a single dose of AMG 986 either IV or PO. The 5 IV cohorts started at a 0.5 mg loading dose over one hour up to the Cohort 5 IV dosage of a 60 mg loading dose over 1 hour and a 360 mg maintenance dose lasting 23 hours. The 6 PO cohorts started at a single 5 mg dose up to the Cohort 6 PO dose of 650 mg.	Part B: Placebo Pooled n=16 Participants Healthy participants were administered placebo either IV for 4 consecutive days or PO for 7 days to match the 2 IV cohorts and 6 PO cohorts of AMG 986.	Part B: AMG 986 Pooled n=50 Participants Healthy participants were administered AMG 986 either IV or PO. IV cohort 1 was administered a loading dose of 6 mg over one hour followed by maintenance doses of 36 mg lasting 23 hours on day 1 and 38 mg lasting 24 hours on days 2-4. IV cohort 2 was administered a loading dose of 60 mg lasting one hour followed by maintenance doses of 360 mg lasting 23 hours on day 1 and 376 mg lasting 24 hours on days 2-4. The 6 PO cohorts started at 5 mg for 7 days up to Cohort 6 PO dose of 650 mg for 7 days.	Part C: HFrEF Placebo n=7 Participants Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from days 1-21.	Part C: HFpEF Placebo n=1 Participants Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO placebo tablet daily from days 1-21.	Part C: HFrEF AMG 986 n=17 Participants Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.	Part C: HFpEF AMG 986 n=3 Participants Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.	Total n=182 Participants Total of all reporting groups
Age, Continuous	37.2 years STANDARD_DEVIATION 9.4 • n=5 Participants	39.5 years STANDARD_DEVIATION 9.8 • n=7 Participants	36.9 years STANDARD_DEVIATION 10.0 • n=5 Participants	37.4 years STANDARD_DEVIATION 9.8 • n=4 Participants	61.6 years STANDARD_DEVIATION 10.1 • n=21 Participants	73.0 years n=8 Participants	64.3 years STANDARD_DEVIATION 7.8 • n=8 Participants	69.0 years STANDARD_DEVIATION 1.0 • n=24 Participants	42.3 years STANDARD_DEVIATION 13.4 • n=42 Participants
Age, Customized 18-64 years	22 Participants n=5 Participants	66 Participants n=7 Participants	16 Participants n=5 Participants	50 Participants n=4 Participants	4 Participants n=21 Participants	0 Participants n=8 Participants	11 Participants n=8 Participants	0 Participants n=24 Participants	169 Participants n=42 Participants
Age, Customized 65-84 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants	1 Participants n=8 Participants	6 Participants n=8 Participants	3 Participants n=24 Participants	13 Participants n=42 Participants
Age, Customized 85 years and over	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	7 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants	1 Participants n=8 Participants	3 Participants n=8 Participants	2 Participants n=24 Participants	17 Participants n=42 Participants
Sex: Female, Male Male	22 Participants n=5 Participants	59 Participants n=7 Participants	16 Participants n=5 Participants	49 Participants n=4 Participants	4 Participants n=21 Participants	0 Participants n=8 Participants	14 Participants n=8 Participants	1 Participants n=24 Participants	165 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants	22 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	35 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants	44 Participants n=7 Participants	15 Participants n=5 Participants	45 Participants n=4 Participants	6 Participants n=21 Participants	1 Participants n=8 Participants	17 Participants n=8 Participants	2 Participants n=24 Participants	146 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	1 Participants n=42 Participants
Race/Ethnicity, Customized Asian	3 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants	11 Participants n=4 Participants	2 Participants n=21 Participants	0 Participants n=8 Participants	2 Participants n=8 Participants	0 Participants n=24 Participants	30 Participants n=42 Participants
Race/Ethnicity, Customized Black	5 Participants n=5 Participants	16 Participants n=7 Participants	5 Participants n=5 Participants	17 Participants n=4 Participants	2 Participants n=21 Participants	0 Participants n=8 Participants	7 Participants n=8 Participants	2 Participants n=24 Participants	54 Participants n=42 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	1 Participants n=42 Participants
Race/Ethnicity, Customized White	11 Participants n=5 Participants	35 Participants n=7 Participants	5 Participants n=5 Participants	18 Participants n=4 Participants	3 Participants n=21 Participants	1 Participants n=8 Participants	8 Participants n=8 Participants	0 Participants n=24 Participants	81 Participants n=42 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	8 Participants n=7 Participants	0 Participants n=5 Participants	3 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants	13 Participants n=42 Participants
Race/Ethnicity, Customized Multiple	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	3 Participants n=42 Participants

PRIMARY outcome

Timeframe: Part A: Day 1 up to Day 31 Part B: Day 1 up to Day 37 Part C: Day 1 up to Day 51

Population: All participants who received at least 1 dose of study drug

Outcome measures

Outcome measures
Measure	Part A: Placebo Pooled n=22 Participants Healthy participants were administered placebo either intravenously (IV) or by mouth (PO) to match the 5 IV cohorts and 6 PO cohorts of AMG 986.	Part A: AMG 986 Pooled n=66 Participants Healthy participants were administered a single dose of AMG 986 either IV or PO. The 5 IV cohorts started at a 0.5 mg loading dose over one hour up to the Cohort 5 IV dosage of a 60 mg loading dose over 1 hour and a 360 mg maintenance dose lasting 23 hours. The 6 PO cohorts started at a single 5 mg dose up to the Cohort 6 PO dose of 650 mg.	Part B: Placebo Pooled n=16 Participants Healthy participants were administered placebo either IV for 4 consecutive days or PO for 7 days to match the 2 IV cohorts and 6 PO cohorts of AMG 986.	Part B: AMG 986 Pooled n=50 Participants Healthy participants were administered AMG 986 either IV or PO. IV cohort 1 was administered a loading dose of 6 mg over one hour followed by maintenance doses of 36 mg lasting 23 hours on day 1 and 38 mg lasting 24 hours on days 2-4. IV cohort 2 was administered a loading dose of 60 mg lasting one hour followed by maintenance doses of 360 mg lasting 23 hours on day 1 and 376 mg lasting 24 hours on days 2-4. The 6 PO cohorts started at 5 mg for 7 days up to Cohort 6 PO dose of 650 mg for 7 days.	Part C: HFrEF Placebo n=7 Participants Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from days 1-21.	Part C: HFpEF Placebo n=1 Participants Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO placebo tablet daily from days 1-21.	Part C: HFrEF AMG 986 n=16 Participants Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.	Part C: HFpEF AMG 986 n=3 Participants Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.
Participants With Treatment Emergent Adverse Events (TEAE) All treatment-emergent adverse events (TEAEs)	3 Participants	11 Participants	2 Participants	7 Participants	2 Participants	1 Participants	6 Participants	3 Participants
Participants With Treatment Emergent Adverse Events (TEAE) Serious adverse events	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Participants With Treatment Emergent Adverse Events (TEAE) TEAEs leading to discontinuation of study drug	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	2 Participants
Participants With Treatment Emergent Adverse Events (TEAE) Fatal adverse events	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30

Population: Participants who received study drug with available LVEF at each time point

Heart failure (HF) refers to a clinical condition in which the cardiac output is insufficient to meet the metabolic needs of body organs and is marked by cardiac systolic and/or diastolic dysfunction. Heart failure with predominantly systolic dysfunction, which is identifiable as decreased contraction, is more aptly described as heart failure with reduced ejection fraction (HFrEF). Ejection fraction is a measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction and is measured by echocardiogram.

Outcome measures

Outcome measures
Measure	Part A: Placebo Pooled n=7 Participants Healthy participants were administered placebo either intravenously (IV) or by mouth (PO) to match the 5 IV cohorts and 6 PO cohorts of AMG 986.	Part A: AMG 986 Pooled n=16 Participants Healthy participants were administered a single dose of AMG 986 either IV or PO. The 5 IV cohorts started at a 0.5 mg loading dose over one hour up to the Cohort 5 IV dosage of a 60 mg loading dose over 1 hour and a 360 mg maintenance dose lasting 23 hours. The 6 PO cohorts started at a single 5 mg dose up to the Cohort 6 PO dose of 650 mg.	Part B: Placebo Pooled Healthy participants were administered placebo either IV for 4 consecutive days or PO for 7 days to match the 2 IV cohorts and 6 PO cohorts of AMG 986.	Part B: AMG 986 Pooled Healthy participants were administered AMG 986 either IV or PO. IV cohort 1 was administered a loading dose of 6 mg over one hour followed by maintenance doses of 36 mg lasting 23 hours on day 1 and 38 mg lasting 24 hours on days 2-4. IV cohort 2 was administered a loading dose of 60 mg lasting one hour followed by maintenance doses of 360 mg lasting 23 hours on day 1 and 376 mg lasting 24 hours on days 2-4. The 6 PO cohorts started at 5 mg for 7 days up to Cohort 6 PO dose of 650 mg for 7 days.	Part C: HFrEF Placebo Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from days 1-21.	Part C: HFpEF Placebo Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO placebo tablet daily from days 1-21.	Part C: HFrEF AMG 986 Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.	Part C: HFpEF AMG 986 Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.
Left Ventricular Ejection Fraction by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort Baseline	33.300 percent of total left ventricular blood Standard Deviation 8.420	28.380 percent of total left ventricular blood Standard Deviation 6.483	—	—	—	—	—	—
Left Ventricular Ejection Fraction by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort Day 8	34.900 percent of total left ventricular blood Standard Deviation 12.441	32.553 percent of total left ventricular blood Standard Deviation 7.055	—	—	—	—	—	—
Left Ventricular Ejection Fraction by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort Day 15	33.533 percent of total left ventricular blood Standard Deviation 9.194	31.614 percent of total left ventricular blood Standard Deviation 7.154	—	—	—	—	—	—
Left Ventricular Ejection Fraction by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort Day 21	33.550 percent of total left ventricular blood Standard Deviation 8.896	31.436 percent of total left ventricular blood Standard Deviation 5.953	—	—	—	—	—	—
Left Ventricular Ejection Fraction by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort Day 30	33.171 percent of total left ventricular blood Standard Deviation 8.140	31.987 percent of total left ventricular blood Standard Deviation 7.036	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30

Population: Participants who received study drug with available data at each time point

Stroke volume is the amount of blood pumped by the left ventricle of the heart in one contraction reported by volumetric method of disks (MoD) assessment.

Outcome measures

Outcome measures
Measure	Part A: Placebo Pooled n=7 Participants Healthy participants were administered placebo either intravenously (IV) or by mouth (PO) to match the 5 IV cohorts and 6 PO cohorts of AMG 986.	Part A: AMG 986 Pooled n=16 Participants Healthy participants were administered a single dose of AMG 986 either IV or PO. The 5 IV cohorts started at a 0.5 mg loading dose over one hour up to the Cohort 5 IV dosage of a 60 mg loading dose over 1 hour and a 360 mg maintenance dose lasting 23 hours. The 6 PO cohorts started at a single 5 mg dose up to the Cohort 6 PO dose of 650 mg.	Part B: Placebo Pooled Healthy participants were administered placebo either IV for 4 consecutive days or PO for 7 days to match the 2 IV cohorts and 6 PO cohorts of AMG 986.	Part B: AMG 986 Pooled Healthy participants were administered AMG 986 either IV or PO. IV cohort 1 was administered a loading dose of 6 mg over one hour followed by maintenance doses of 36 mg lasting 23 hours on day 1 and 38 mg lasting 24 hours on days 2-4. IV cohort 2 was administered a loading dose of 60 mg lasting one hour followed by maintenance doses of 360 mg lasting 23 hours on day 1 and 376 mg lasting 24 hours on days 2-4. The 6 PO cohorts started at 5 mg for 7 days up to Cohort 6 PO dose of 650 mg for 7 days.	Part C: HFrEF Placebo Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO placebo tablet daily from days 1-21.	Part C: HFpEF Placebo Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO placebo tablet daily from days 1-21.	Part C: HFrEF AMG 986 Participants with heart failure with reduced ejection fraction (HFrEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.	Part C: HFpEF AMG 986 Participants with heart failure with preserved ejection fraction (HFpEF) were administered a single PO AMG 986 tablet daily from days 1-21 in ascending doses of 10 mg for days 1-7, 30 mg for days 8-14 and 100 mg for days 15-21.
Stroke Volume (Method of Disks, Volumetric Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort Baseline	53.387 mL Standard Deviation 16.995	40.461 mL Standard Deviation 14.193	—	—	—	—	—	—
Stroke Volume (Method of Disks, Volumetric Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort Day 8	55.185 mL Standard Deviation 19.158	46.130 mL Standard Deviation 13.927	—	—	—	—	—	—
Stroke Volume (Method of Disks, Volumetric Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort Day 15	52.673 mL Standard Deviation 19.514	46.784 mL Standard Deviation 14.348	—	—	—	—	—	—
Stroke Volume (Method of Disks, Volumetric Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort Day 21	54.113 mL Standard Deviation 18.789	44.014 mL Standard Deviation 12.051	—	—	—	—	—	—
Stroke Volume (Method of Disks, Volumetric Assessment) by Visit for Part C Heart Failure With Reduced Ejection Fraction (HFrEF) Cohort Day 30	53.621 mL Standard Deviation 19.258	44.634 mL Standard Deviation 13.491	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 predose), Day 8, Day 15, Day 21, Day 30

Population: Participants who received study drug with available data at each time point

Stroke volume is the amount of blood pumped by the left ventricle of the heart in one contraction as measured using left ventricular outflow tract (LVOT) Doppler assessment.