LEVosimendan to Improve Exercise Limitation in Patients With PH-HFpEF

This is a Phase 3, double-blind, randomized, placebo-controlled study of oral levosimendan in patients with PH-HFpEF. There will be a Screening Period of up to 30 days. Subjects will provide written informed consent prior to completing any study procedures. Upon meeting all eligibility criteria, patients will continue to the 12-week randomized, double-blind treatment phase. Approximately 230 subjects will be randomized in a 1:1 ratio to receive an oral dose of levosimendan or placebo

All randomized subjects will have the option to enter the 92-week OLE following the completion of all study events at Week 12.

Inclusion criteria

• Men or women, greater than or equal to18 to 85 years of age.
• NYHA Class II or III or NYHA class IV symptoms.
• A diagnosis of World Health Organization (WHO) Group 2 PH-HFpEF with qualifying hemodynamics
• Qualifying Baseline RHC.
• Qualifying echocardiogram
• Qualifying 6-MWD
• A 48-hour ambulatory cardiac rhythm monitor during the Screening Period.
• Requirements related to child bearing potential, contraception, and egg/sperm donation

Exclusion criteria

• A diagnosis of PH WHO Groups 1, 3, 4, or 5.
• Echocardiographic evidence for hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or infiltrative cardiomyopathy
• Structural heart repair or replacement of the aortic valve or mitral valve (surgical or percutaneous). OR, planned valve intervention. OR, the presence of significant valve disease
• A diagnosis of pre-existing lung disease
• History of severe allergic or anaphylactic reaction or hypersensitivity to the excipients in the investigational product.
• Major surgery within 60 days.
• Prior heart, lung, or heart-lung transplants or life expectancy of <12 months
• History of clinically significant other diseases that may limit or complicate participation in the study.