Clinical Trials

Inclusion Criteria:

1. Men or women, greater than or equal to18 to 85 years of age.

2. NYHA Class II or III or ambulatory NYHA class IV symptoms.

3. A diagnosis of World Health Organization (WHO) Group 2 PH-HFpEF with qualifying
hemodynamics

4. A qualifying Baseline RHC performed within 120 days. The RHC can be a historical RHC
done prior to study consent.

5. A qualifying echocardiogram performed within 30 days showing an LVEF greater than or
equal to 40%

6. A qualifying 6-MWD of at least 100 meters, but not more than 450 meters at Screening

7. A 48-hour ambulatory cardiac rhythm monitor during the Screening Period to establish
the resting heart rate (HR) and rhythm.

8. Chronic medications for heart failure with preserved ejection fraction (HFpEF) or
other serious underlying cardiac or pulmonary conditions should be administered at a
stable dose for greater than or equal to 30 days prior to the day of the Baseline
6-MWT.

9. Female subjects of childbearing potential must have a negative urine pregnancy test
result at the Screening Visit and a negative urine pregnancy test and must not be
pregnant, lactating, or planning a pregnancy from the Screening Visit to 7 months
after the last dose of study drug.

10. Female subjects of childbearing potential will be included if they are either sexually
inactive (abstinent) for 90 days prior to the first dose of study drug, or are using a
highly effective birth control method

11. Female subjects of nonchildbearing potential will be included if they meet the
following definition of nonchildbearing potential: are either surgically sterile or
postmenopausal.

12. Male patients with female partners of childbearing potential must use highly effective
methods of birth control during their participation in the study and for a period of 4
months after the last dose of study drug.

13. Patients must agree to abstain from egg or sperm donation through 7 months for female
patients and 4 months for male patients after administration of the last dose of study
drug.

14. Ability to adhere to study visit schedule and understand and comply with all protocol
requirements.

15. Signed informed consent document indicating that they understand the purpose and
procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

1. A diagnosis of PH WHO Groups 1, 3, 4, or 5.

2. Walking activity that is limited by anything other than shortness of breath or fatigue
attributed to PH-HFpEF.

3. Echocardiographic evidence for hypertrophic cardiomyopathy, restrictive
cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or infiltrative
cardiomyopathy

4. Structural heart repair or replacement of the aortic valve or mitral valve (surgical
or percutaneous) within the past 12 months. OR, planned valve intervention in the next
6 months. OR, the presence of echocardiographic findings of significant valve disease
as assessed from the qualifying echocardiogram

5. Any of the following clinical laboratory values within 30 days as specified:

1. Hemoglobin <10 g/dL per local laboratory.

2. Serum alanine aminotransferase or aspartate aminotransferase levels > 3 × upper
limit of normal (ULN) or total bilirubin > 3 × ULN.

3. Electrocardiogram (ECG) with a QTcF > 450 msec for males and > 470 msec for females
at Screening and Baseline in the absence of right bundle branch block.

4. Platelet count < 75,000/mm^3.

6. A diagnosis of pre-existing lung disease

7. Recent documentation of significant underlying lung disease

8. Documentation of pulmonary thromboembolism in the last 12 months

9. Cardiovascular co-morbidities

10. Receipt of any approved pulmonary arterial hypertension-specific therapies

11. Hospitalization for any indication within 30 days

12. Receipt of any intravenous (IV) inotropes within 30 days

13. Body mass index greater than or equal to 50 kg/m^2.

14. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m^2

15. Known history of chronic liver disease

16. Prior exposure to levosimendan

17. Current enrollment in or completion of any other investigational product study within
30 days of Screening.

18. Initiation of an exercise program for cardiopulmonary rehabilitation within 45 days

19. History of severe allergic or anaphylactic reaction or hypersensitivity to the
excipients in the investigational product.

20. Major surgery within 60 days. Subjects must have completely recovered from any
previous surgery.

21. Prior heart, lung, or heart-lung transplants or life expectancy of <12 months

22. Pregnancy or breastfeeding in females

23. History of active malignancy, with the exception of fully treated basal cell
carcinoma, cervical carcinoma in situ, or squamous cell carcinomas of the skin.

24. History of clinically significant other diseases that may limit or complicate
participation in the study.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 11/21/23. Questions regarding updates should be directed to the study team contact.