Overview
This study will evaluate the efficacy of TNX-103 (oral levosimendan) compared with placebo in subjects with PH-HFpEF as measured by the change in 6-Minute Walk Distance (6 MWD; Day 1 to Week 12).
Description
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.
Eligibility
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.
