Trial Outcomes & Findings for Exploratory Study of Danicamtiv in Patients With Primary Dilated Cardiomyopathy (DCM) Due to Genetic Variants or Other Causalities (NCT NCT04572893)

NCT ID: NCT04572893

Last Updated: 2025-05-21

Results Overview

An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 41 participants
• Primary outcome timeframe: From first dose to 30 days post last dose (Up to approximately 15 weeks)
• Results posted on: 2025-05-21

Participant Flow

Part B will commence after a participant completes Part A and opts to continue onto Part B. Individual participant doses for Part B will be based on systolic ejection time increase in Part A.

Participant milestones

Measure	Part A - MYH7 - MYK-491 Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 Participants with MYH7 variant received Danicamtiv after meeting eligibility criteria	Part B - TTN - MYK-491 Participants with TTN variant received Danicamtiv after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 Participants with DCM-Non genetic received Danicamtiv after meeting eligibility criteria
Part A STARTED	12	14	5	10	0	0	0
Part A Started Part B	8	7	0	4	0	0	0
Part A COMPLETED	11	14	5	10	0	0	0
Part A NOT COMPLETED	1	0	0	0	0	0	0
Part B STARTED	0	0	0	0	8	7	4
Part B COMPLETED	0	0	0	0	0	0	0
Part B NOT COMPLETED	0	0	0	0	8	7	4

Reasons for withdrawal

Measure	Part A - MYH7 - MYK-491 Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 Participants with MYH7 variant received Danicamtiv after meeting eligibility criteria	Part B - TTN - MYK-491 Participants with TTN variant received Danicamtiv after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 Participants with DCM-Non genetic received Danicamtiv after meeting eligibility criteria
Part A Adverse Event	1	0	0	0	0	0	0
Part B Withdrawal by Subject	0	0	0	0	0	1	0
Part B Study terminated by sponsor	0	0	0	0	7	5	3
Part B Lost to Follow-up	0	0	0	0	0	0	1
Part B Adverse Event	0	0	0	0	1	1	0

Baseline Characteristics

Exploratory Study of Danicamtiv in Patients With Primary Dilated Cardiomyopathy (DCM) Due to Genetic Variants or Other Causalities

Baseline characteristics by cohort

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Total n=41 Participants Total of all reporting groups
Age, Categorical <=18 years	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
Age, Categorical Between 18 and 65 years	11 Participants n=5 Participants	12 Participants n=7 Participants	4 Participants n=5 Participants	9 Participants n=4 Participants	36 Participants n=21 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	15 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	10 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants	26 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	13 Participants n=7 Participants	3 Participants n=5 Participants	10 Participants n=4 Participants	35 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	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
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 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	0 Participants n=4 Participants	0 Participants n=21 Participants
Race/Ethnicity, Customized White	11 Participants n=5 Participants	14 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=4 Participants	38 Participants n=21 Participants
Race/Ethnicity, Customized Uknown	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

PRIMARY outcome

Timeframe: From first dose to 30 days post last dose (Up to approximately 15 weeks)

Population: All treated participants in Part A as pre-specified in protocol.

An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Number of Participants With Adverse Events (AEs) in Part A	9 Participants	9 Participants	4 Participants	4 Participants	—	—	—

PRIMARY outcome

Timeframe: From first dose to 30 days post last dose (Up to approximately 15 weeks)

Population: All treated participants in Part A as pre-specified in protocol.

An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability or permanent damage, is a congenital anomaly/birth defect, is an important medical event.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Number of Participants With Serious Adverse Events (SAEs) in Part A	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—

PRIMARY outcome

Timeframe: From first dose to 14 days post last dose (Up to approximately 13 weeks)

Population: All treated participants in Part A as pre-specified in protocol

Number of participants with safety laboratory assessments by intensity. Mild=An event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; Moderate= An event causing sufficient discomfort and interferes with normal everyday activities.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Number of Participants With Safety Laboratory Assessments by Intensity in Part A Blood creatinine increased Moderate	0 Participants	0 Participants	1 Participants	0 Participants	—	—	—
Number of Participants With Safety Laboratory Assessments by Intensity in Part A Alanine aminotransferase increased Mild	1 Participants	0 Participants	1 Participants	0 Participants	—	—	—
Number of Participants With Safety Laboratory Assessments by Intensity in Part A Aspartate aminotransferase increased Mild	1 Participants	0 Participants	1 Participants	0 Participants	—	—	—
Number of Participants With Safety Laboratory Assessments by Intensity in Part A Fibrin D dimer increased Moderate	0 Participants	1 Participants	0 Participants	0 Participants	—	—	—
Number of Participants With Safety Laboratory Assessments by Intensity in Part A Hyperkalaemia Mild	0 Participants	1 Participants	0 Participants	0 Participants	—	—	—
Number of Participants With Safety Laboratory Assessments by Intensity in Part A Hyperkalaemia Moderate	0 Participants	0 Participants	1 Participants	0 Participants	—	—	—

PRIMARY outcome

Timeframe: From first dose to 30 days post last dose (Up to approximately 15 weeks)

Population: All treated participants in Part A as pre-specified in protocol

Number of participants with clinically significant changes in physical examinations.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Number of Participants With Clinically Significant Changes in Physical Examinations in Part A	0 Participants	1 Participants	0 Participants	0 Participants	—	—	—

PRIMARY outcome

Timeframe: From first dose to 30 days post last dose (Up to approximately 15 weeks)

Population: All treated participants in Part A as pre-specified in protocol

Number of participants with clinically significant changes in vital signs.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Number of Participants With Clinically Significant Changes in Vital Signs in Part A	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—

PRIMARY outcome

Timeframe: From first dose to 30 days post last dose (Up to approximately 15 weeks)

Population: All treated participants in Part A as pre-specified in protocol

Number of participants with clinically significant changes in 12-lead ECG recordings.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Number of Participants With Clinically Significant Changes in 12-Lead ECG Recordings in Part A	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—

PRIMARY outcome

Timeframe: From first dose to 14 days post last dose (Up to approximately 13 weeks)

Population: All treated participants in Part A as pre-specified in protocol

An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.

Mild=An event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities; Moderate= An event causing sufficient discomfort and interferes with normal everyday activities.

Severe= An event preventing normal everyday activities. (An AE that is assessed as severe should not be confused with a SAE. Severe is a category utilized for rating the intensity of an event; and both AEs and SAEs can be assessed as severe.)

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Intensity in Part A Mild	8 Participants	6 Participants	3 Participants	4 Participants	—	—	—
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Intensity in Part A Moderate	0 Participants	1 Participants	1 Participants	0 Participants	—	—	—
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Intensity in Part A Severe	0 Participants	0 Participants	0 Participants	0 Participants	—	—	—

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=4 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Left Ventricular Ejection Time (LVET) Change From Baseline Early termination	-23.0 msec Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	13.5 msec Standard Deviation 44.4	-1.4 msec Standard Deviation 20.5	-14.3 msec Standard Deviation 35.2
Transthoracic Echo (TTE) Left Ventricular Ejection Time (LVET) Change From Baseline End of treatment period 1	12.1 msec Standard Deviation 23.7	7.4 msec Standard Deviation 28.8	-3.5 msec Standard Deviation 8.7	3.3 msec Standard Deviation 36.3	—	—	—
Transthoracic Echo (TTE) Left Ventricular Ejection Time (LVET) Change From Baseline End of treatment period 2	29.4 msec Standard Deviation 31.0	29.0 msec Standard Deviation 25.4	-5.6 msec Standard Deviation 18.2	15.2 msec Standard Deviation 54.4	—	—	—
Transthoracic Echo (TTE) Left Ventricular Ejection Time (LVET) Change From Baseline week 2	—	—	—	—	38.3 msec Standard Deviation 30.0	44.3 msec Standard Deviation 16.3	20.3 msec Standard Deviation 34.5
Transthoracic Echo (TTE) Left Ventricular Ejection Time (LVET) Change From Baseline week 6	—	—	—	—	25.3 msec Standard Deviation 22.3	53.3 msec Standard Deviation 43.6	20.5 msec Standard Deviation 67.2
Transthoracic Echo (TTE) Left Ventricular Ejection Time (LVET) Change From Baseline week 12	—	—	—	—	32.1 msec Standard Deviation 27.4	38.2 msec Standard Deviation 33.5	44.0 msec Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Left Ventricular Ejection Time (LVET) Change From Baseline week 24	—	—	—	—	39.8 msec Standard Deviation 46.3	59.8 msec Standard Deviation 39.5	—
Transthoracic Echo (TTE) Left Ventricular Ejection Time (LVET) Change From Baseline week 36	—	—	—	—	—	47.5 msec Standard Deviation 9.2	—
Transthoracic Echo (TTE) Left Ventricular Ejection Time (LVET) Change From Baseline week 48	—	—	—	—	42.3 msec Standard Deviation 40.3	30.3 msec Standard Deviation 34.0	—

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=11 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=4 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Left Ventricular Stroke Volume (LVSV) Change From Baseline End of treatment period 1	10.581 mL Standard Deviation 9.814	5.628 mL Standard Deviation 3.127	1.855 mL Standard Deviation 7.979	-5.897 mL Standard Deviation 17.237	—	—	—
Transthoracic Echo (TTE) Left Ventricular Stroke Volume (LVSV) Change From Baseline End of treatment period 2	10.151 mL Standard Deviation 19.585	1.243 mL Standard Deviation 14.275	1.050 mL Standard Deviation 13.379	2.172 mL Standard Deviation 20.000	—	—	—
Transthoracic Echo (TTE) Left Ventricular Stroke Volume (LVSV) Change From Baseline week 2	—	—	—	—	15.576 mL Standard Deviation 11.932	-7.600 mL Standard Deviation 14.358	-15.678 mL Standard Deviation 18.882
Transthoracic Echo (TTE) Left Ventricular Stroke Volume (LVSV) Change From Baseline week 6	—	—	—	—	7.778 mL Standard Deviation 21.508	18.313 mL Standard Deviation 14.697	16.500 mL Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Left Ventricular Stroke Volume (LVSV) Change From Baseline week 12	—	—	—	—	19.410 mL Standard Deviation 21.832	24.853 mL Standard Deviation 18.181	22.320 mL Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Left Ventricular Stroke Volume (LVSV) Change From Baseline week 24	—	—	—	—	13.893 mL Standard Deviation 14.892	25.174 mL Standard Deviation 24.052	—
Transthoracic Echo (TTE) Left Ventricular Stroke Volume (LVSV) Change From Baseline week 36	—	—	—	—	—	-20.450 mL Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Left Ventricular Stroke Volume (LVSV) Change From Baseline week 48	—	—	—	—	19.070 mL Standard Deviation 16.317	-6.863 mL Standard Deviation 12.464	—
Transthoracic Echo (TTE) Left Ventricular Stroke Volume (LVSV) Change From Baseline Early termination	0.650 mL Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	2.684 mL Standard Deviation 30.133	-11.136 mL Standard Deviation 14.539	5.533 mL Standard Deviation 20.941

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 42, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=4 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=3 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Left Ventricular Ejection Fraction (LVEF) Change From Baseline Early termination	-3.20 percentage Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	-2.94 percentage Standard Deviation 4.65	3.99 percentage Standard Deviation 9.55	4.13 percentage Standard Deviation 5.87
Transthoracic Echo (TTE) Left Ventricular Ejection Fraction (LVEF) Change From Baseline End of treatment period 1	4.78 percentage Standard Deviation 7.40	4.94 percentage Standard Deviation 7.08	-0.75 percentage Standard Deviation 3.06	2.47 percentage Standard Deviation 6.14	—	—	—
Transthoracic Echo (TTE) Left Ventricular Ejection Fraction (LVEF) Change From Baseline End of treatment period 2	8.84 percentage Standard Deviation 6.43	5.94 percentage Standard Deviation 6.15	1.37 percentage Standard Deviation 5.36	4.84 percentage Standard Deviation 10.00	—	—	—
Transthoracic Echo (TTE) Left Ventricular Ejection Fraction (LVEF) Change From Baseline week 2	—	—	—	—	5.53 percentage Standard Deviation 10.31	4.21 percentage Standard Deviation 11.03	5.60 percentage Standard Deviation 2.12
Transthoracic Echo (TTE) Left Ventricular Ejection Fraction (LVEF) Change From Baseline week 6	—	—	—	—	3.31 percentage Standard Deviation 5.85	-0.40 percentage Standard Deviation 7.83	14.05 percentage Standard Deviation 18.03
Transthoracic Echo (TTE) Left Ventricular Ejection Fraction (LVEF) Change From Baseline week 12	—	—	—	—	2.44 percentage Standard Deviation 5.39	1.77 percentage Standard Deviation 5.26	7.60 percentage Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Left Ventricular Ejection Fraction (LVEF) Change From Baseline week 24	—	—	—	—	-2.78 percentage Standard Deviation 0.59	2.24 percentage Standard Deviation 8.58	—
Transthoracic Echo (TTE) Left Ventricular Ejection Fraction (LVEF) Change From Baseline week 36	—	—	—	—	—	10.80 percentage Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Left Ventricular Ejection Fraction (LVEF) Change From Baseline Week 42	—	—	—	—	—	23.60 percentage Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Left Ventricular Ejection Fraction (LVEF) Change From Baseline week 48	—	—	—	—	3.85 percentage Standard Deviation 4.75	7.12 percentage Standard Deviation 11.12	—

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 42, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=4 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Left Ventricular Global Longitudinal Strain (LVGLS) Change From Baseline End of treatment period 1	-1.41 percentage Standard Deviation 2.79	-0.79 percentage Standard Deviation 2.31	-0.32 percentage Standard Deviation 2.81	-0.36 percentage Standard Deviation 1.63	—	—	—
Transthoracic Echo (TTE) Left Ventricular Global Longitudinal Strain (LVGLS) Change From Baseline End of treatment period 2	-2.05 percentage Standard Deviation 2.05	-1.21 percentage Standard Deviation 2.23	-1.92 percentage Standard Deviation 2.00	-0.95 percentage Standard Deviation 2.46	—	—	—
Transthoracic Echo (TTE) Left Ventricular Global Longitudinal Strain (LVGLS) Change From Baseline week 2	—	—	—	—	-1.60 percentage Standard Deviation 2.59	-1.84 percentage Standard Deviation 1.66	-1.80 percentage Standard Deviation 2.63
Transthoracic Echo (TTE) Left Ventricular Global Longitudinal Strain (LVGLS) Change From Baseline week 6	—	—	—	—	-2.18 percentage Standard Deviation 2.53	-1.90 percentage Standard Deviation 1.11	-3.65 percentage Standard Deviation 0.49
Transthoracic Echo (TTE) Left Ventricular Global Longitudinal Strain (LVGLS) Change From Baseline week 12	—	—	—	—	-2.34 percentage Standard Deviation 2.03	-2.00 percentage Standard Deviation 2.34	-4.00 percentage Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Left Ventricular Global Longitudinal Strain (LVGLS) Change From Baseline week 24	—	—	—	—	0.02 percentage Standard Deviation 1.25	-2.62 percentage Standard Deviation 2.66	—
Transthoracic Echo (TTE) Left Ventricular Global Longitudinal Strain (LVGLS) Change From Baseline week 36	—	—	—	—	—	-2.50 percentage Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Left Ventricular Global Longitudinal Strain (LVGLS) Change From Baseline Week 42	—	—	—	—	—	-7.70 percentage Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Left Ventricular Global Longitudinal Strain (LVGLS) Change From Baseline week 48	—	—	—	—	-2.77 percentage Standard Deviation 1.99	-4.33 percentage Standard Deviation 1.30	—
Transthoracic Echo (TTE) Left Ventricular Global Longitudinal Strain (LVGLS) Change From Baseline Early termination	-0.70 percentage Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	0.01 percentage Standard Deviation 2.12	-1.31 percentage Standard Deviation 1.41	-1.90 percentage Standard Deviation 1.81

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 42, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=10 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=10 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=4 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=7 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=4 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Left Ventricular Global Circumferential Strain (LVGCS) Change From Baseline Early termination	0.40 percentage Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	0.54 percentage Standard Deviation 5.50	-1.52 percentage Standard Deviation 2.38	0.40 percentage Standard Deviation 5.23
Transthoracic Echo (TTE) Left Ventricular Global Circumferential Strain (LVGCS) Change From Baseline End of treatment period 1	-3.62 percentage Standard Deviation 3.73	0.58 percentage Standard Deviation 2.83	-4.10 percentage Standard Deviation 4.07	0.15 percentage Standard Deviation 4.47	—	—	—
Transthoracic Echo (TTE) Left Ventricular Global Circumferential Strain (LVGCS) Change From Baseline End of treatment period 2	-4.00 percentage Standard Deviation 3.17	-1.45 percentage Standard Deviation 3.32	-2.08 percentage Standard Deviation 1.25	-0.78 percentage Standard Deviation 3.87	—	—	—
Transthoracic Echo (TTE) Left Ventricular Global Circumferential Strain (LVGCS) Change From Baseline week 2	—	—	—	—	-5.16 percentage Standard Deviation 4.55	-3.00 percentage Standard Deviation 3.64	-3.25 percentage Standard Deviation 5.30
Transthoracic Echo (TTE) Left Ventricular Global Circumferential Strain (LVGCS) Change From Baseline week 6	—	—	—	—	-4.07 percentage Standard Deviation 3.43	-4.68 percentage Standard Deviation 1.11	-0.10 percentage Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Left Ventricular Global Circumferential Strain (LVGCS) Change From Baseline week 12	—	—	—	—	-3.80 percentage Standard Deviation 1.26	-0.94 percentage Standard Deviation 2.65	0.00 percentage Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Left Ventricular Global Circumferential Strain (LVGCS) Change From Baseline week 24	—	—	—	—	-2.64 percentage Standard Deviation 4.72	-0.88 percentage Standard Deviation 1.94	—
Transthoracic Echo (TTE) Left Ventricular Global Circumferential Strain (LVGCS) Change From Baseline week 36	—	—	—	—	—	-2.60 percentage Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Left Ventricular Global Circumferential Strain (LVGCS) Change From Baseline Week 42	—	—	—	—	—	-6.00 percentage Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Left Ventricular Global Circumferential Strain (LVGCS) Change From Baseline week 48	—	—	—	—	-4.05 percentage Standard Deviation 3.13	-3.98 percentage Standard Deviation 3.43	—

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=11 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=13 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=2 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Lateral Change From Baseline End of treatment period 1	0.23 cm/s Standard Deviation 1.90	-0.12 cm/s Standard Deviation 0.77	1.15 cm/s Standard Deviation 0.66	0.22 cm/s Standard Deviation 1.62	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Lateral Change From Baseline End of treatment period 2	1.01 cm/s Standard Deviation 1.75	0.53 cm/s Standard Deviation 1.57	1.40 cm/s Standard Deviation 1.38	-0.10 cm/s Standard Deviation 1.99	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Lateral Change From Baseline week 2	—	—	—	—	-0.04 cm/s Standard Deviation 1.62	-0.14 cm/s Standard Deviation 0.88	-0.95 cm/s Standard Deviation 0.78
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Lateral Change From Baseline week 6	—	—	—	—	0.34 cm/s Standard Deviation 0.84	0.08 cm/s Standard Deviation 0.59	-0.80 cm/s Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Lateral Change From Baseline week 12	—	—	—	—	0.57 cm/s Standard Deviation 1.26	-0.03 cm/s Standard Deviation 1.29	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Lateral Change From Baseline week 24	—	—	—	—	-0.55 cm/s Standard Deviation 1.33	0.18 cm/s Standard Deviation 0.65	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Lateral Change From Baseline week 36	—	—	—	—	—	-0.30 cm/s Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Lateral Change From Baseline week 48	—	—	—	—	1.25 cm/s Standard Deviation 1.35	0.10 cm/s Standard Deviation 0.46	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Lateral Change From Baseline Early termination	-2.30 cm/s Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	0.14 cm/s Standard Deviation 1.43	0.67 cm/s Standard Deviation 1.39	-1.20 cm/s Standard Deviation 0.57

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=13 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=3 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Septal Change From Baseline week 36	—	—	—	—	—	-1.40 cm/s Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Septal Change From Baseline week 48	—	—	—	—	1.22 cm/s Standard Deviation 1.27	0.07 cm/s Standard Deviation 1.14	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Septal Change From Baseline End of treatment period 1	0.56 cm/s Standard Deviation 1.05	0.03 cm/s Standard Deviation 0.50	0.78 cm/s Standard Deviation 0.63	0.06 cm/s Standard Deviation 0.66	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Septal Change From Baseline End of treatment period 2	0.53 cm/s Standard Deviation 0.42	0.20 cm/s Standard Deviation 0.62	1.04 cm/s Standard Deviation 1.57	-0.20 cm/s Standard Deviation 0.94	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Septal Change From Baseline week 2	—	—	—	—	0.24 cm/s Standard Deviation 0.90	0.06 cm/s Standard Deviation 0.58	0.20 cm/s Standard Deviation 1.31
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Septal Change From Baseline week 6	—	—	—	—	0.95 cm/s Standard Deviation 0.89	0.50 cm/s Standard Deviation 1.39	-0.05 cm/s Standard Deviation 1.34
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Septal Change From Baseline week 12	—	—	—	—	0.77 cm/s Standard Deviation 0.83	-0.12 cm/s Standard Deviation 0.74	1.30 cm/s Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Septal Change From Baseline week 24	—	—	—	—	0.17 cm/s Standard Deviation 0.53	0.17 cm/s Standard Deviation 0.97	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) S Prime Septal Change From Baseline Early termination	0.40 cm/s Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	0.40 cm/s Standard Deviation 1.53	0.10 cm/s Standard Deviation 0.77	0.67 cm/s Standard Deviation 1.00

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=13 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=7 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=3 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Diameter (LVESD) Change From Baseline End of treatment period 1	-0.15 mm Standard Deviation 4.07	-2.84 mm Standard Deviation 3.47	0.10 mm Standard Deviation 1.44	-1.77 mm Standard Deviation 5.60	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Diameter (LVESD) Change From Baseline End of treatment period 2	-3.14 mm Standard Deviation 5.97	-5.48 mm Standard Deviation 4.83	-3.60 mm Standard Deviation 3.48	-2.20 mm Standard Deviation 6.03	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Diameter (LVESD) Change From Baseline week 2	—	—	—	—	-0.90 mm Standard Deviation 4.25	-5.94 mm Standard Deviation 3.74	-4.43 mm Standard Deviation 9.40
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Diameter (LVESD) Change From Baseline week 6	—	—	—	—	-0.17 mm Standard Deviation 6.01	-5.93 mm Standard Deviation 4.76	-2.20 mm Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Diameter (LVESD) Change From Baseline week 12	—	—	—	—	-0.92 mm Standard Deviation 4.67	-4.18 mm Standard Deviation 4.75	-1.60 mm Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Diameter (LVESD) Change From Baseline week 24	—	—	—	—	-0.07 mm Standard Deviation 6.04	-6.12 mm Standard Deviation 4.18	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Diameter (LVESD) Change From Baseline week 36	—	—	—	—	—	-5.80 mm Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Diameter (LVESD) Change From Baseline week 48	—	—	—	—	2.90 mm Standard Deviation 7.07	-4.90 mm Standard Deviation 3.53	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Diameter (LVESD) Change From Baseline Early termination	-1.50 mm Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	1.33 mm Standard Deviation 10.57	-0.77 mm Standard Deviation 3.86	-0.60 mm Standard Deviation 5.36

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 42, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=4 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=3 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Volumen Index (LVESVi) Change From Baseline End of treatment period 1	-8.3128 mL/m^2 Standard Deviation 9.2045	-2.8341 mL/m^2 Standard Deviation 10.6672	1.5998 mL/m^2 Standard Deviation 2.6613	-3.1748 mL/m^2 Standard Deviation 6.3863	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Volumen Index (LVESVi) Change From Baseline End of treatment period 2	-9.0315 mL/m^2 Standard Deviation 10.6354	-7.0016 mL/m^2 Standard Deviation 8.8423	-1.7459 mL/m^2 Standard Deviation 6.9756	-4.3387 mL/m^2 Standard Deviation 8.9773	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Volumen Index (LVESVi) Change From Baseline week 2	—	—	—	—	-16.6661 mL/m^2 Standard Deviation 27.1117	-6.1675 mL/m^2 Standard Deviation 12.9178	-3.7087 mL/m^2 Standard Deviation 2.2142
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Volumen Index (LVESVi) Change From Baseline week 6	—	—	—	—	-6.8323 mL/m^2 Standard Deviation 14.6055	-7.9134 mL/m^2 Standard Deviation 10.2267	-13.2403 mL/m^2 Standard Deviation 18.8755
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Volumen Index (LVESVi) Change From Baseline week 12	—	—	—	—	-5.5205 mL/m^2 Standard Deviation 9.5934	-9.9285 mL/m^2 Standard Deviation 14.1805	-0.9776 mL/m^2 Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Volumen Index (LVESVi) Change From Baseline week 24	—	—	—	—	-2.2674 mL/m^2 Standard Deviation 14.6852	-6.6309 mL/m^2 Standard Deviation 19.3049	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Volumen Index (LVESVi) Change From Baseline week 36	—	—	—	—	—	-21.4681 mL/m^2 Standard Deviation 6.5099	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Volumen Index (LVESVi) Change From Baseline Week 42	—	—	—	—	—	-29.9173 mL/m^2 Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Volumen Index (LVESVi) Change From Baseline week 48	—	—	—	—	-13.5827 mL/m^2 Standard Deviation 21.5043	-18.4947 mL/m^2 Standard Deviation 12.9649	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Systolic Volumen Index (LVESVi) Change From Baseline Early termination	1.2208 mL/m^2 Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	-2.3523 mL/m^2 Standard Deviation 14.4189	-6.7128 mL/m^2 Standard Deviation 15.2440	2.9170 mL/m^2 Standard Deviation 6.0452

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=13 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=4 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Diameter (LVEDD) Change From Baseline End of treatment period 1	0.48 mm Standard Deviation 3.61	-2.49 mm Standard Deviation 3.51	-0.60 mm Standard Deviation 3.91	-1.37 mm Standard Deviation 5.14	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Diameter (LVEDD) Change From Baseline End of treatment period 2	-0.85 mm Standard Deviation 4.36	-3.12 mm Standard Deviation 3.34	-3.50 mm Standard Deviation 3.84	-1.77 mm Standard Deviation 4.60	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Diameter (LVEDD) Change From Baseline week 2	—	—	—	—	-5.11 mm Standard Deviation 9.22	-3.56 mm Standard Deviation 4.03	-5.00 mm Standard Deviation 7.04
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Diameter (LVEDD) Change From Baseline week 6	—	—	—	—	-1.75 mm Standard Deviation 3.34	-3.10 mm Standard Deviation 2.61	0.30 mm Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Diameter (LVEDD) Change From Baseline week 12	—	—	—	—	-2.09 mm Standard Deviation 3.58	-0.17 mm Standard Deviation 2.64	0.90 mm Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Diameter (LVEDD) Change From Baseline week 24	—	—	—	—	-2.10 mm Standard Deviation 2.50	-2.86 mm Standard Deviation 5.87	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Diameter (LVEDD) Change From Baseline week 36	—	—	—	—	—	-3.10 mm Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Diameter (LVEDD) Change From Baseline Week 42	—	—	—	—	—	-1.50 mm Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Diameter (LVEDD) Change From Baseline week 48	—	—	—	—	-3.40 mm Standard Deviation 3.64	-2.13 mm Standard Deviation 3.40	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Diameter (LVEDD) Change From Baseline Early termination	3.60 mm Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	-1.97 mm Standard Deviation 5.36	0.46 mm Standard Deviation 3.40	2.70 mm Standard Deviation 1.13

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 42, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=4 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=3 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Volumen Index (LVEDVi) Change From Baseline End of treatment period 1	-7.3006 m1/m2 Standard Deviation 7.0043	0.4855 m1/m2 Standard Deviation 10.8288	1.3937 m1/m2 Standard Deviation 3.9810	-3.6715 m1/m2 Standard Deviation 8.4975	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Volumen Index (LVEDVi) Change From Baseline End of treatment period 2	-4.3719 m1/m2 Standard Deviation 11.6238	-4.4642 m1/m2 Standard Deviation 12.9621	-1.1050 m1/m2 Standard Deviation 6.1575	-2.1417 m1/m2 Standard Deviation 12.8270	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Volumen Index (LVEDVi) Change From Baseline week 2	—	—	—	—	-19.7184 m1/m2 Standard Deviation 31.0876	-6.7773 m1/m2 Standard Deviation 10.3963	0.2596 m1/m2 Standard Deviation 0.0152
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Volumen Index (LVEDVi) Change From Baseline week 6	—	—	—	—	-6.2694 m1/m2 Standard Deviation 17.5060	-12.9208 m1/m2 Standard Deviation 11.0202	-11.4771 m1/m2 Standard Deviation 18.4933
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Volumen Index (LVEDVi) Change From Baseline week 12	—	—	—	—	-5.2247 m1/m2 Standard Deviation 11.4301	-11.7627 m1/m2 Standard Deviation 17.1607	7.4828 m1/m2 Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Volumen Index (LVEDVi) Change From Baseline week 24	—	—	—	—	-5.9020 m1/m2 Standard Deviation 20.7779	-6.2700 m1/m2 Standard Deviation 24.3104	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Volumen Index (LVEDVi) Change From Baseline week 36	—	—	—	—	—	-13.0453 m1/m2 Standard Deviation 5.3813	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Volumen Index (LVEDVi) Change From Baseline Week 42	—	—	—	—	—	-11.8121 m1/m2 Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Volumen Index (LVEDVi) Change From Baseline week 48	—	—	—	—	-14.3351 m1/m2 Standard Deviation 24.7973	-18.5657 m1/m2 Standard Deviation 6.0845	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) Left Ventricular End-Diastolic Volumen Index (LVEDVi) Change From Baseline Early termination	-1.6197 m1/m2 Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	-7.2323 m1/m2 Standard Deviation 24.2148	-6.7050 m1/m2 Standard Deviation 17.2581	8.3887 m1/m2 Standard Deviation 3.3592

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=11 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=12 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=6 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=3 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Lateral Change From Baseline End of treatment period 1	0.55 cm/s Standard Deviation 1.63	0.37 cm/s Standard Deviation 2.51	1.23 cm/s Standard Deviation 1.21	0.46 cm/s Standard Deviation 3.27	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Lateral Change From Baseline End of treatment period 2	0.51 cm/s Standard Deviation 1.50	0.58 cm/s Standard Deviation 2.97	2.60 cm/s Standard Deviation 3.38	-0.66 cm/s Standard Deviation 2.23	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Lateral Change From Baseline week 2	—	—	—	—	0.23 cm/s Standard Deviation 2.77	0.42 cm/s Standard Deviation 1.47	-1.30 cm/s Standard Deviation 1.51
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Lateral Change From Baseline week 6	—	—	—	—	0.43 cm/s Standard Deviation 1.18	-0.14 cm/s Standard Deviation 1.29	-1.30 cm/s Standard Deviation 0.99
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Lateral Change From Baseline week 12	—	—	—	—	0.83 cm/s Standard Deviation 1.99	-1.48 cm/s Standard Deviation 2.36	-3.20 cm/s Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Lateral Change From Baseline week 24	—	—	—	—	0.15 cm/s Standard Deviation 1.52	-0.40 cm/s Standard Deviation 2.09	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Lateral Change From Baseline week 36	—	—	—	—	—	-1.80 cm/s Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Lateral Change From Baseline week 48	—	—	—	—	2.25 cm/s Standard Deviation 1.89	-0.30 cm/s Standard Deviation 1.60	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Lateral Change From Baseline Early termination	-0.60 cm/s Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	0.20 cm/s Standard Deviation 2.85	0.37 cm/s Standard Deviation 2.28	2.23 cm/s Standard Deviation 2.16

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=11 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=3 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Septal Change From Baseline End of treatment period 1	0.75 cm/s Standard Deviation 1.66	0.26 cm/s Standard Deviation 1.62	-0.05 cm/s Standard Deviation 1.35	-0.73 cm/s Standard Deviation 1.30	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Septal Change From Baseline End of treatment period 2	-0.04 cm/s Standard Deviation 0.86	0.28 cm/s Standard Deviation 1.59	0.84 cm/s Standard Deviation 1.12	-0.32 cm/s Standard Deviation 1.32	—	—	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Septal Change From Baseline week 2	—	—	—	—	0.51 cm/s Standard Deviation 1.43	-0.84 cm/s Standard Deviation 1.52	-0.17 cm/s Standard Deviation 1.12
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Septal Change From Baseline week 6	—	—	—	—	0.58 cm/s Standard Deviation 1.12	-0.73 cm/s Standard Deviation 1.94	-0.10 cm/s Standard Deviation 2.97
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Septal Change From Baseline week 12	—	—	—	—	0.60 cm/s Standard Deviation 1.16	-0.86 cm/s Standard Deviation 1.23	1.90 cm/s Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Septal Change From Baseline week 24	—	—	—	—	-0.65 cm/s Standard Deviation 0.76	-0.75 cm/s Standard Deviation 0.91	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Septal Change From Baseline week 36	—	—	—	—	—	-5.10 cm/s Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Septal Change From Baseline week 48	—	—	—	—	1.75 cm/s Standard Deviation 1.32	-1.50 cm/s Standard Deviation 1.93	—
Transthoracic Echo (TTE) Tissue Doppler Imaging (TDI) E Prime Septal Change From Baseline Early termination	0.60 cm/s Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	1.04 cm/s Standard Deviation 1.65	0.04 cm/s Standard Deviation 1.25	1.03 cm/s Standard Deviation 2.58

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=13 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=7 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=3 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) E/E Prime Average Ratio Change From Baseline End of treatment period 1	-2.45 E/E prime ratio Standard Deviation 3.16	0.07 E/E prime ratio Standard Deviation 3.67	-0.20 E/E prime ratio Standard Deviation 4.46	0.41 E/E prime ratio Standard Deviation 3.23	—	—	—
Transthoracic Echo (TTE) E/E Prime Average Ratio Change From Baseline End of treatment period 2	-2.15 E/E prime ratio Standard Deviation 2.88	0.45 E/E prime ratio Standard Deviation 2.99	-2.16 E/E prime ratio Standard Deviation 3.92	1.03 E/E prime ratio Standard Deviation 2.60	—	—	—
Transthoracic Echo (TTE) E/E Prime Average Ratio Change From Baseline week 2	—	—	—	—	-1.43 E/E prime ratio Standard Deviation 4.37	-0.03 E/E prime ratio Standard Deviation 4.40	-0.03 E/E prime ratio Standard Deviation 0.47
Transthoracic Echo (TTE) E/E Prime Average Ratio Change From Baseline week 6	—	—	—	—	-1.19 E/E prime ratio Standard Deviation 4.09	-0.15 E/E prime ratio Standard Deviation 5.41	1.25 E/E prime ratio Standard Deviation 1.20
Transthoracic Echo (TTE) E/E Prime Average Ratio Change From Baseline week 12	—	—	—	—	-2.24 E/E prime ratio Standard Deviation 1.56	-0.47 E/E prime ratio Standard Deviation 3.85	0.60 E/E prime ratio Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) E/E Prime Average Ratio Change From Baseline week 24	—	—	—	—	0.07 E/E prime ratio Standard Deviation 4.67	-0.66 E/E prime ratio Standard Deviation 4.24	—
Transthoracic Echo (TTE) E/E Prime Average Ratio Change From Baseline week 36	—	—	—	—	—	10.70 E/E prime ratio Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) E/E Prime Average Ratio Change From Baseline week 48	—	—	—	—	-4.88 E/E prime ratio Standard Deviation 2.38	-1.00 E/E prime ratio Standard Deviation 3.89	—
Transthoracic Echo (TTE) E/E Prime Average Ratio Change From Baseline Early termination	-0.90 E/E prime ratio Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	-1.07 E/E prime ratio Standard Deviation 3.30	-0.51 E/E prime ratio Standard Deviation 3.91	-0.03 E/E prime ratio Standard Deviation 0.93

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=11 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=12 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=7 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=6 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=3 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) E/E Prime Lateral Ratio Change From Baseline End of treatment period 1	-1.29 E/E prime ratio Standard Deviation 1.72	-0.08 E/E prime ratio Standard Deviation 3.68	-1.80 E/E prime ratio Standard Deviation 5.60	-0.49 E/E prime ratio Standard Deviation 3.94	—	—	—
Transthoracic Echo (TTE) E/E Prime Lateral Ratio Change From Baseline End of treatment period 2	-1.14 E/E prime ratio Standard Deviation 2.23	0.12 E/E prime ratio Standard Deviation 2.94	-3.58 E/E prime ratio Standard Deviation 4.88	0.73 E/E prime ratio Standard Deviation 3.93	—	—	—
Transthoracic Echo (TTE) E/E Prime Lateral Ratio Change From Baseline week 2	—	—	—	—	-1.07 E/E prime ratio Standard Deviation 2.88	-1.00 E/E prime ratio Standard Deviation 1.98	0.77 E/E prime ratio Standard Deviation 1.42
Transthoracic Echo (TTE) E/E Prime Lateral Ratio Change From Baseline week 6	—	—	—	—	-0.75 E/E prime ratio Standard Deviation 4.23	-1.34 E/E prime ratio Standard Deviation 2.15	1.80 E/E prime ratio Standard Deviation 2.55
Transthoracic Echo (TTE) E/E Prime Lateral Ratio Change From Baseline week 12	—	—	—	—	-2.17 E/E prime ratio Standard Deviation 2.45	2.48 E/E prime ratio Standard Deviation 5.43	4.00 E/E prime ratio Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) E/E Prime Lateral Ratio Change From Baseline week 24	—	—	—	—	-0.45 E/E prime ratio Standard Deviation 3.99	-0.47 E/E prime ratio Standard Deviation 2.94	—
Transthoracic Echo (TTE) E/E Prime Lateral Ratio Change From Baseline week 36	—	—	—	—	—	5.00 E/E prime ratio Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) E/E Prime Lateral Ratio Change From Baseline week 48	—	—	—	—	-4.08 E/E prime ratio Standard Deviation 3.06	-1.47 E/E prime ratio Standard Deviation 1.44	—
Transthoracic Echo (TTE) E/E Prime Lateral Ratio Change From Baseline Early termination	0.20 E/E prime ratio Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	-0.91 E/E prime ratio Standard Deviation 3.39	0.75 E/E prime ratio Standard Deviation 5.92	0.10 E/E prime ratio Standard Deviation 0.62

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=11 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=7 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=3 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) E/E Prime Septal Ratio Change From Baseline End of treatment period 1	-3.12 E/E prime ratio Standard Deviation 4.51	-0.91 E/E prime ratio Standard Deviation 3.78	0.65 E/E prime ratio Standard Deviation 2.89	1.86 E/E prime ratio Standard Deviation 2.30	—	—	—
Transthoracic Echo (TTE) E/E Prime Septal Ratio Change From Baseline End of treatment period 2	-1.45 E/E prime ratio Standard Deviation 2.14	0.07 E/E prime ratio Standard Deviation 4.00	-1.38 E/E prime ratio Standard Deviation 2.82	1.32 E/E prime ratio Standard Deviation 3.07	—	—	—
Transthoracic Echo (TTE) E/E Prime Septal Ratio Change From Baseline week 2	—	—	—	—	-1.77 E/E prime ratio Standard Deviation 6.75	1.50 E/E prime ratio Standard Deviation 9.41	-0.83 E/E prime ratio Standard Deviation 1.57
Transthoracic Echo (TTE) E/E Prime Septal Ratio Change From Baseline week 6	—	—	—	—	-1.27 E/E prime ratio Standard Deviation 4.43	1.33 E/E prime ratio Standard Deviation 10.61	0.65 E/E prime ratio Standard Deviation 0.07
Transthoracic Echo (TTE) E/E Prime Septal Ratio Change From Baseline week 12	—	—	—	—	-2.27 E/E prime ratio Standard Deviation 3.53	-1.30 E/E prime ratio Standard Deviation 3.68	-2.70 E/E prime ratio Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) E/E Prime Septal Ratio Change From Baseline week 24	—	—	—	—	0.70 E/E prime ratio Standard Deviation 5.41	-2.03 E/E prime ratio Standard Deviation 7.68	—
Transthoracic Echo (TTE) E/E Prime Septal Ratio Change From Baseline week 36	—	—	—	—	—	16.50 E/E prime ratio Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) E/E Prime Septal Ratio Change From Baseline week 48	—	—	—	—	-5.68 E/E prime ratio Standard Deviation 4.89	0.05 E/E prime ratio Standard Deviation 7.37	—
Transthoracic Echo (TTE) E/E Prime Septal Ratio Change From Baseline Early termination	-2.00 E/E prime ratio Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	-1.19 E/E prime ratio Standard Deviation 3.67	-1.19 E/E prime ratio Standard Deviation 4.95	-0.27 E/E prime ratio Standard Deviation 2.20

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=11 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=11 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=5 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=10 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=6 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=6 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=4 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Ratio of Peak Inflow Velocities in Early and Late Diastole - E/A Change From Baseline End of treatment period 1	0.02 E/A ratio Standard Deviation 0.16	-0.01 E/A ratio Standard Deviation 0.32	-0.10 E/A ratio Standard Deviation 0.10	0.04 E/A ratio Standard Deviation 0.11	—	—	—
Transthoracic Echo (TTE) Ratio of Peak Inflow Velocities in Early and Late Diastole - E/A Change From Baseline End of treatment period 2	-0.16 E/A ratio Standard Deviation 0.40	-0.08 E/A ratio Standard Deviation 0.37	-0.26 E/A ratio Standard Deviation 0.54	-0.04 E/A ratio Standard Deviation 0.15	—	—	—
Transthoracic Echo (TTE) Ratio of Peak Inflow Velocities in Early and Late Diastole - E/A Change From Baseline week 2	—	—	—	—	0.07 E/A ratio Standard Deviation 0.92	-0.32 E/A ratio Standard Deviation 0.40	-0.12 E/A ratio Standard Deviation 0.21
Transthoracic Echo (TTE) Ratio of Peak Inflow Velocities in Early and Late Diastole - E/A Change From Baseline week 6	—	—	—	—	-0.25 E/A ratio Standard Deviation 0.45	-0.58 E/A ratio Standard Deviation 0.77	0.15 E/A ratio Standard Deviation 0.21
Transthoracic Echo (TTE) Ratio of Peak Inflow Velocities in Early and Late Diastole - E/A Change From Baseline week 12	—	—	—	—	-0.23 E/A ratio Standard Deviation 0.50	-0.76 E/A ratio Standard Deviation 0.70	0.20 E/A ratio Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Ratio of Peak Inflow Velocities in Early and Late Diastole - E/A Change From Baseline week 24	—	—	—	—	0.00 E/A ratio Standard Deviation 0.10	-0.53 E/A ratio Standard Deviation 0.78	—
Transthoracic Echo (TTE) Ratio of Peak Inflow Velocities in Early and Late Diastole - E/A Change From Baseline week 36	—	—	—	—	—	0.20 E/A ratio Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Ratio of Peak Inflow Velocities in Early and Late Diastole - E/A Change From Baseline week 48	—	—	—	—	-0.40 E/A ratio Standard Deviation 0.52	-0.77 E/A ratio Standard Deviation 0.85	—
Transthoracic Echo (TTE) Ratio of Peak Inflow Velocities in Early and Late Diastole - E/A Change From Baseline Early termination	0.70 E/A ratio Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	-0.10 E/A ratio Standard Deviation 0.32	-0.37 E/A ratio Standard Deviation 0.52	0.17 E/A ratio Standard Deviation 0.06

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=4 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=9 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=3 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Left Atrial Minimum Volume (LAminV) Change From Baseline week 6	—	—	—	—	3.430 mL Standard Deviation 9.313	-10.938 mL Standard Deviation 22.821	1.680 mL Standard Deviation 5.374
Transthoracic Echo (TTE) Left Atrial Minimum Volume (LAminV) Change From Baseline week 12	—	—	—	—	-3.409 mL Standard Deviation 13.577	-13.953 mL Standard Deviation 24.798	9.950 mL Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Left Atrial Minimum Volume (LAminV) Change From Baseline End of treatment period 1	-2.545 mL Standard Deviation 4.182	-0.374 mL Standard Deviation 8.947	-3.663 mL Standard Deviation 9.552	-0.563 mL Standard Deviation 3.670	—	—	—
Transthoracic Echo (TTE) Left Atrial Minimum Volume (LAminV) Change From Baseline End of treatment period 2	-3.985 mL Standard Deviation 5.681	0.049 mL Standard Deviation 8.529	-3.993 mL Standard Deviation 5.672	-2.866 mL Standard Deviation 6.613	—	—	—
Transthoracic Echo (TTE) Left Atrial Minimum Volume (LAminV) Change From Baseline week 2	—	—	—	—	0.509 mL Standard Deviation 11.279	-3.807 mL Standard Deviation 9.917	2.817 mL Standard Deviation 8.224
Transthoracic Echo (TTE) Left Atrial Minimum Volume (LAminV) Change From Baseline week 24	—	—	—	—	-2.858 mL Standard Deviation 16.826	-5.214 mL Standard Deviation 32.177	—
Transthoracic Echo (TTE) Left Atrial Minimum Volume (LAminV) Change From Baseline week 36	—	—	—	—	—	-16.410 mL Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Left Atrial Minimum Volume (LAminV) Change From Baseline Week 42	—	—	—	—	—	-27.640 mL Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Left Atrial Minimum Volume (LAminV) Change From Baseline week 48	—	—	—	—	-7.560 mL Standard Deviation 7.287	-19.843 mL Standard Deviation 24.404	—
Transthoracic Echo (TTE) Left Atrial Minimum Volume (LAminV) Change From Baseline Early termination	12.030 mL Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	1.313 mL Standard Deviation 13.248	-4.793 mL Standard Deviation 19.027	10.607 mL Standard Deviation 3.279

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=4 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=9 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=3 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Left Atrial Maximum Volume Index (LAmaxVi) Change From Baseline End of treatment period 1	-0.6427 mL/m^2 Standard Deviation 5.0007	0.9860 mL/m^2 Standard Deviation 7.1462	-0.6320 mL/m^2 Standard Deviation 9.1208	-0.0084 mL/m^2 Standard Deviation 2.4459	—	—	—
Transthoracic Echo (TTE) Left Atrial Maximum Volume Index (LAmaxVi) Change From Baseline End of treatment period 2	-0.3419 mL/m^2 Standard Deviation 4.2365	1.1617 mL/m^2 Standard Deviation 6.0815	-1.1870 mL/m^2 Standard Deviation 7.2047	-0.2139 mL/m^2 Standard Deviation 2.5533	—	—	—
Transthoracic Echo (TTE) Left Atrial Maximum Volume Index (LAmaxVi) Change From Baseline week 2	—	—	—	—	0.1346 mL/m^2 Standard Deviation 6.4456	-0.1818 mL/m^2 Standard Deviation 5.1802	2.3315 mL/m^2 Standard Deviation 9.2253
Transthoracic Echo (TTE) Left Atrial Maximum Volume Index (LAmaxVi) Change From Baseline week 6	—	—	—	—	1.1887 mL/m^2 Standard Deviation 4.2647	-5.5545 mL/m^2 Standard Deviation 13.4164	-0.5969 mL/m^2 Standard Deviation 10.1570
Transthoracic Echo (TTE) Left Atrial Maximum Volume Index (LAmaxVi) Change From Baseline week 12	—	—	—	—	-1.9834 mL/m^2 Standard Deviation 9.0618	-7.1717 mL/m^2 Standard Deviation 14.8684	7.8293 mL/m^2 Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Left Atrial Maximum Volume Index (LAmaxVi) Change From Baseline week 24	—	—	—	—	-2.3145 mL/m^2 Standard Deviation 11.3192	-1.8423 mL/m^2 Standard Deviation 17.8500	—
Transthoracic Echo (TTE) Left Atrial Maximum Volume Index (LAmaxVi) Change From Baseline week 36	—	—	—	—	—	-13.3385 mL/m^2 Standard Deviation 3.1173	—
Transthoracic Echo (TTE) Left Atrial Maximum Volume Index (LAmaxVi) Change From Baseline Week 42	—	—	—	—	—	-11.7208 mL/m^2 Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Left Atrial Maximum Volume Index (LAmaxVi) Change From Baseline week 48	—	—	—	—	-2.4524 mL/m^2 Standard Deviation 3.4679	-11.2887 mL/m^2 Standard Deviation 15.6892	—
Transthoracic Echo (TTE) Left Atrial Maximum Volume Index (LAmaxVi) Change From Baseline Early termination	8.1892 mL/m^2 Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	-0.0097 mL/m^2 Standard Deviation 6.8537	-1.4975 mL/m^2 Standard Deviation 9.7454	6.5957 mL/m^2 Standard Deviation 3.9106

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=4 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=9 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=3 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Left Atrial Emptying Fraction (LAEF) Change From Baseline End of treatment period 1	5.617 Percent change Standard Deviation 13.459	4.675 Percent change Standard Deviation 12.173	2.687 Percent change Standard Deviation 26.913	2.489 Percent change Standard Deviation 10.953	—	—	—
Transthoracic Echo (TTE) Left Atrial Emptying Fraction (LAEF) Change From Baseline End of treatment period 2	15.504 Percent change Standard Deviation 18.234	9.870 Percent change Standard Deviation 15.019	8.102 Percent change Standard Deviation 21.513	9.655 Percent change Standard Deviation 14.789	—	—	—
Transthoracic Echo (TTE) Left Atrial Emptying Fraction (LAEF) Change From Baseline week 2	—	—	—	—	-1.903 Percent change Standard Deviation 19.042	15.609 Percent change Standard Deviation 10.759	1.058 Percent change Standard Deviation 6.753
Transthoracic Echo (TTE) Left Atrial Emptying Fraction (LAEF) Change From Baseline week 6	—	—	—	—	-9.410 Percent change Standard Deviation 20.950	21.196 Percent change Standard Deviation 24.108	-7.265 Percent change Standard Deviation 24.267
Transthoracic Echo (TTE) Left Atrial Emptying Fraction (LAEF) Change From Baseline week 12	—	—	—	—	5.089 Percent change Standard Deviation 17.898	24.306 Percent change Standard Deviation 30.693	-6.694 Percent change Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Left Atrial Emptying Fraction (LAEF) Change From Baseline week 24	—	—	—	—	6.522 Percent change Standard Deviation 23.635	19.181 Percent change Standard Deviation 31.252	—
Transthoracic Echo (TTE) Left Atrial Emptying Fraction (LAEF) Change From Baseline week 36	—	—	—	—	—	2.595 Percent change Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Left Atrial Emptying Fraction (LAEF) Change From Baseline Week 42	—	—	—	—	—	43.996 Percent change Standard Deviation NA Insufficient number of participants to calculate standard deviation	—
Transthoracic Echo (TTE) Left Atrial Emptying Fraction (LAEF) Change From Baseline week 48	—	—	—	—	23.815 Percent change Standard Deviation 26.494	27.568 Percent change Standard Deviation 24.279	—
Transthoracic Echo (TTE) Left Atrial Emptying Fraction (LAEF) Change From Baseline Early termination	-7.060 Percent change Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	-0.711 Percent change Standard Deviation 30.276	11.267 Percent change Standard Deviation 25.412	-6.924 Percent change Standard Deviation 11.148

SECONDARY outcome

Timeframe: Part A: Baseline, end of treatment period 1. end of treatment period 2, early termination; Part B: Baseline, weeks 2, 6, 12, 24, 36, 48, and early termination

Population: All treated participants with baseline and post baseline measurements at the specified timepoints

Baseline is defined as the last non-missing result prior to the first dose of study medication. for part B, baseline is defined as visit 1B regardless of rescreening. Treatment periods 1 and 2 are 5 to 8 days. Higher LAFI values are considered better left atrial function while lower LFAI values may indicate left atrial dysfunction.

Outcome measures

Measure	Part A - MYH7 - MYK-491 n=12 Participants Participants with myosin heavy chain 7 (MYH7) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - TTN - MYK-491 n=14 Participants Participants with titin (TTN) variant received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Genetic - MYK-491 n=4 Participants Participants with dilated cardiomyopathy (DCM)-Genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part A - DCM-Non Genetic - MYK-491 n=9 Participants Participants with dilated cardiomyopathy (DCM)-Non genetic received Danicamtiv. Study drug will be administered orally BID for at least 5 days and up to 8 days for each Treatment Period	Part B - MYH7 - MYK-491 n=8 Participants Participants with MYH7 variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - TTN - MYK-491 n=7 Participants Participants with TTN variant received Danicamtiv orally BID after meeting eligibility criteria	Part B - DCM-Non Genetic - MYK-491 n=3 Participants Participants with DCM-Non genetic received Danicamtiv orally BID after meeting eligibility criteria
Transthoracic Echo (TTE) Left Atrial Function Index (LAFI) Change From Baseline week 48	—	—	—	—	6.3041 Index Standard Deviation 18.4543	12.8222 Index Standard Deviation 14.0703	—
Transthoracic Echo (TTE) Left Atrial Function Index (LAFI) Change From Baseline Early termination	-11.0849 Index Standard Deviation NA Insufficient number of participants to calculate standard deviation	—	—	—	0.3925 Index Standard Deviation 23.9350	2.4252 Index Standard Deviation 10.4948	-20.4736 Index Standard Deviation 4.7293
Transthoracic Echo (TTE) Left Atrial Function Index (LAFI) Change From Baseline End of treatment period 1	5.2299 Index Standard Deviation 5.3847	1.6645 Index Standard Deviation 11.9891	-0.4600 Index Standard Deviation 1.6721	0.3524 Index Standard Deviation 5.0864	—	—	—
Transthoracic Echo (TTE) Left Atrial Function Index (LAFI) Change From Baseline End of treatment period 2	11.1434 Index Standard Deviation 10.5287	6.8482 Index Standard Deviation 13.2805	1.6243 Index Standard Deviation 5.5803	3.6366 Index Standard Deviation 6.4861	—	—	—
Transthoracic Echo (TTE) Left Atrial Function Index (LAFI) Change From Baseline week 2	—	—	—	—	4.1989 Index Standard Deviation 10.0937	5.6654 Index Standard Deviation 7.6211	-10.2619 Index Standard Deviation 21.2810
Transthoracic Echo (TTE) Left Atrial Function Index (LAFI) Change From Baseline week 6	—	—	—	—	0.7215 Index Standard Deviation 23.0068	9.9039 Index Standard Deviation 8.9999	1.3624 Index Standard Deviation 15.4676
Transthoracic Echo (TTE) Left Atrial Function Index (LAFI) Change From Baseline week 12	—	—	—	—	5.3578 Index Standard Deviation 14.5382	8.4149 Index Standard Deviation 7.3469	-22.1266 Index Standard Deviation NA Insufficient number of participants to calculate standard deviation
Transthoracic Echo (TTE) Left Atrial Function Index (LAFI) Change From Baseline week 24	—	—	—	—	-4.8648 Index Standard Deviation 19.3724	8.1890 Index Standard Deviation 8.8584	—
Transthoracic Echo (TTE) Left Atrial Function Index (LAFI) Change From Baseline week 36	—	—	—	—	—	8.6083 Index Standard Deviation 8.6083	—

Adverse Events

Part A - MYH7 - MYK-491 25 mg BID

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part A - TTN - MYK-491 25 mg BID

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part A - DCM-Genetic - MYK-491 25 mg BID

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part A - DCM-Non Genetic - MYK-491 25 mg BID

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A - MYH7 - MYK-491 50 mg BID

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part A - TTN - MYK-491 50 mg BID

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part A - DCM-Genetic - MYK-491 50 mg BID

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A - DCM-Non Genetic - MYK-491 50 mg BID

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A - DCM-Genetic - MYK-491 10 mg BID

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part A - DCM-Non Genetic - MYK-491 10 mg BID

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part B - MYH7 - MYK-491 25 mg BID

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part B - MYH7 - MYK-491 50 mg BID

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Part B - TTN - MYK-491 50 mg BID

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Part B - DCM-Non Genetic - MYK-491 50 mg BID

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part B - MYH7 - MYK-491 75 mg BID

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part B - TTN - MYK-491 75 mg BID

Serious events: 2 serious events

Other events: 4 other events

Deaths: 0 deaths

Part B - DCM-Non Genetic - MYK-491 75 mg BID

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	Part A - MYH7 - MYK-491 25 mg BID n=12 participants at risk Participants with MYH7 variant received 25 mg BID Danicamtiv	Part A - TTN - MYK-491 25 mg BID n=14 participants at risk Participants with TTN variant received 25 mg BID Danicamtiv	Part A - DCM-Genetic - MYK-491 25 mg BID n=5 participants at risk Participants with DCM-Genetic variant received 25 mg BID Danicamtiv	Part A - DCM-Non Genetic - MYK-491 25 mg BID n=10 participants at risk Participants with DCM-Non genetic variant received 25 mg BID Danicamtiv	Part A - MYH7 - MYK-491 50 mg BID n=12 participants at risk Participants with MYH7 variant received 50 mg BID Danicamtiv	Part A - TTN - MYK-491 50 mg BID n=14 participants at risk Participants with TTN variant received 50 mg BID Danicamtiv	Part A - DCM-Genetic - MYK-491 50 mg BID n=4 participants at risk Participants with DCM-Genetic variant received 50 mg BID Danicamtiv	Part A - DCM-Non Genetic - MYK-491 50 mg BID n=9 participants at risk Participants with DCM-Non genetic variant received 50 mg BID Danicamtiv	Part A - DCM-Genetic - MYK-491 10 mg BID n=1 participants at risk Participants with DCM-Genetic variant received 10 mg BID Danicamtiv	Part A - DCM-Non Genetic - MYK-491 10 mg BID n=1 participants at risk Participants with DCM-Non genetic variant received 10 mg BID Danicamtiv	Part B - MYH7 - MYK-491 25 mg BID n=1 participants at risk Participants with MYH7 variant received 25 mg BID Danicamtiv	Part B - MYH7 - MYK-491 50 mg BID n=4 participants at risk Participants with MYH7 variant received 50 mg BID Danicamtiv	Part B - TTN - MYK-491 50 mg BID n=4 participants at risk Participants with TTN variant received 50 mg BID Danicamtiv	Part B - DCM-Non Genetic - MYK-491 50 mg BID n=1 participants at risk Participants with DCM-Non genetic variant received 50 mg BID Danicamtiv	Part B - MYH7 - MYK-491 75 mg BID n=5 participants at risk Participants with MYH7 variant received 75 mg BID Danicamtiv	Part B - TTN - MYK-491 75 mg BID n=4 participants at risk Participants with TTN variant received 75 mg BID Danicamtiv	Part B - DCM-Non Genetic - MYK-491 75 mg BID n=3 participants at risk Participants with DCM-Non genetic variant received 75 mg BID Danicamtiv
Cardiac disorders Arrhythmic storm	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Cardiac disorders Cardiac failure congestive	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	33.3% 1/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Cardiac disorders Ventricular fibrillation	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Hepatobiliary disorders Liver injury	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Infections and infestations Urinary tract infection	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Nervous system disorders Transient ischaemic attack	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Renal and urinary disorders Acute kidney injury	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.

Other adverse events

Measure	Part A - MYH7 - MYK-491 25 mg BID n=12 participants at risk Participants with MYH7 variant received 25 mg BID Danicamtiv	Part A - TTN - MYK-491 25 mg BID n=14 participants at risk Participants with TTN variant received 25 mg BID Danicamtiv	Part A - DCM-Genetic - MYK-491 25 mg BID n=5 participants at risk Participants with DCM-Genetic variant received 25 mg BID Danicamtiv	Part A - DCM-Non Genetic - MYK-491 25 mg BID n=10 participants at risk Participants with DCM-Non genetic variant received 25 mg BID Danicamtiv	Part A - MYH7 - MYK-491 50 mg BID n=12 participants at risk Participants with MYH7 variant received 50 mg BID Danicamtiv	Part A - TTN - MYK-491 50 mg BID n=14 participants at risk Participants with TTN variant received 50 mg BID Danicamtiv	Part A - DCM-Genetic - MYK-491 50 mg BID n=4 participants at risk Participants with DCM-Genetic variant received 50 mg BID Danicamtiv	Part A - DCM-Non Genetic - MYK-491 50 mg BID n=9 participants at risk Participants with DCM-Non genetic variant received 50 mg BID Danicamtiv	Part A - DCM-Genetic - MYK-491 10 mg BID n=1 participants at risk Participants with DCM-Genetic variant received 10 mg BID Danicamtiv	Part A - DCM-Non Genetic - MYK-491 10 mg BID n=1 participants at risk Participants with DCM-Non genetic variant received 10 mg BID Danicamtiv	Part B - MYH7 - MYK-491 25 mg BID n=1 participants at risk Participants with MYH7 variant received 25 mg BID Danicamtiv	Part B - MYH7 - MYK-491 50 mg BID n=4 participants at risk Participants with MYH7 variant received 50 mg BID Danicamtiv	Part B - TTN - MYK-491 50 mg BID n=4 participants at risk Participants with TTN variant received 50 mg BID Danicamtiv	Part B - DCM-Non Genetic - MYK-491 50 mg BID n=1 participants at risk Participants with DCM-Non genetic variant received 50 mg BID Danicamtiv	Part B - MYH7 - MYK-491 75 mg BID n=5 participants at risk Participants with MYH7 variant received 75 mg BID Danicamtiv	Part B - TTN - MYK-491 75 mg BID n=4 participants at risk Participants with TTN variant received 75 mg BID Danicamtiv	Part B - DCM-Non Genetic - MYK-491 75 mg BID n=3 participants at risk Participants with DCM-Non genetic variant received 75 mg BID Danicamtiv
Cardiac disorders Atrial flutter	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Cardiac disorders Cardiac failure	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Cardiac disorders Palpitations	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Cardiac disorders Ventricular extrasystoles	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Cardiac disorders Ventricular tachycardia	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Ear and labyrinth disorders Vertigo	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Eye disorders Chalazion	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	7.1% 1/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Gastrointestinal disorders Abdominal pain	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	10.0% 1/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Gastrointestinal disorders Diarrhoea	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	16.7% 2/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	7.1% 1/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Gastrointestinal disorders Dyspepsia	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Gastrointestinal disorders Vomiting	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
General disorders Application site rash	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
General disorders Chills	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
General disorders Fatigue	16.7% 2/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	33.3% 1/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
General disorders Malaise	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
General disorders Non-cardiac chest pain	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	7.1% 1/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
General disorders Pyrexia	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Infections and infestations COVID-19	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	50.0% 2/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	33.3% 1/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Infections and infestations Cystitis	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Infections and infestations Gastroenteritis	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Infections and infestations Influenza	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Infections and infestations Nasopharyngitis	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	100.0% 1/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Infections and infestations Pharyngitis	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Infections and infestations Pneumonia	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Infections and infestations Respiratory tract infection	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	50.0% 2/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Infections and infestations Sinusitis	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Infections and infestations Urinary tract infection	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Infections and infestations Viral upper respiratory tract infection	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Injury, poisoning and procedural complications Accidental overdose	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	10.0% 1/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Injury, poisoning and procedural complications Contusion	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Injury, poisoning and procedural complications Fall	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Injury, poisoning and procedural complications Ligament sprain	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Injury, poisoning and procedural complications Meniscus injury	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Injury, poisoning and procedural complications Overdose	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Investigations Alanine aminotransferase increased	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Investigations Aspartate aminotransferase increased	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Investigations Blood creatine phosphokinase increased	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Investigations Blood creatinine increased	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Investigations Fibrin D dimer increased	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	7.1% 1/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Investigations International normalised ratio increased	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Investigations Liver function test increased	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Investigations SARS-CoV-2 test positive	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Investigations Troponin I increased	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	7.1% 1/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Musculoskeletal and connective tissue disorders Flank pain	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Musculoskeletal and connective tissue disorders Muscle contracture	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	7.1% 1/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	11.1% 1/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	7.1% 1/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Haemangioma of bone	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Nervous system disorders Dizziness	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Nervous system disorders Headache	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	7.1% 1/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	10.0% 1/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Nervous system disorders Hypoaesthesia	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Nervous system disorders Presyncope	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Product Issues Device inappropriate shock delivery	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Psychiatric disorders Adjustment disorder	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Psychiatric disorders Initial insomnia	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Psychiatric disorders Insomnia	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	8.3% 1/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Psychiatric disorders Restlessness	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	7.1% 1/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	7.1% 1/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	11.1% 1/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Skin and subcutaneous tissue disorders Rash pruritic	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Vascular disorders Hot flush	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	20.0% 1/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.
Vascular disorders Hypotension	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/10 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/12 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/14 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/9 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	25.0% 1/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/1 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	0.00% 0/5 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	50.0% 2/4 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.	33.3% 1/3 • All-cause mortality, serious adverse events, and other adverse events are from first dose until the end of the study visit for the participant (Up to approximately 115 weeks) The participant will receive 25mg BID dose in Part A Treatment Period 1 and then the same participant will be up-titrated to 50mg BID or down-titrated to 10mg BID in Part A Treatment Period 2. The Part B starting dose can be either 5 mg BID, 10 mg BID, 25 mg BID, 50 mg BID, or 75 mg BID, and then the same participant will be up-titrated or down-titrated to a dose based on systolic ejection time.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Phone: Please Email:

Email: Clinical.Trials@bms.com

Results disclosure agreements

• Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
• Publication restrictions are in place

Restriction type: OTHER