A Study to Evaluate Whether Macitentan is an Effective and Safe Treatment for Patients With Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease (SERENADE)

This is a study to evaluate whether macitentan is an effective and safe treatment for patients with heart failure with preserved ejection fraction (HFpEF) and pulmonary vascular disease. The primary objective is to evaluate whether macitentan 10 mg reduces N-terminal pro-brain natriuretic peptide (NT-pro-BNP) as compared to placebo in these patients.

Inova Fairfax Hospital

3300 Gallows Road

Falls Church, VA 22042

Dr. Mardi Gomberg, MD

Inclusion Criteria:

• Signs or symptoms of Heart Failure (HF) (NYHA FC I I and II I ) requiring treatment with at least one oral diuretic (any type)
• Left ventricular ejection fraction (LVEF) ≥ 40% (by echocardiography at Screening)
• Structural heart disease consistent with heart failure with preserved ejection fraction (HFpEF) established by echocardiography at Screening
• HF hospitalization within 12 months prior to Screening and/or cardiac catheterization performed within 6 months prior to Screening showing PAWP or LVEDP > 15 mmHg
• Elevated NT-proBNP
• Pulmonary vascular disease or right ventricular dysfunction

Exclusion Criteria:

• Any prior measurement of LVEF < 40%.
• Cardiovascular co-morbidities (e.g., significant unrepaired structural valvular heart disease; acute coronary syndrome, coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) within 3 months of Screening; uncontrolled heart rate from atrial fibrillation or atrial flutter, history of serious life-threatening or hemodynamically significant arrhythmia; history of or anticipated heart transplant or ventricular assist device implantation, etc)
• Systolic blood pressure (SBP) ≥ 180 mmHg, or diastolic blood pressure (DBP) ≥ 110 mmHg during Screening
• Body mass index (BMI) ≥ 45 kg/m2
• Hemoglobin < 100g/L (< 10 g/dl) at Screening.
• Significant parenchymal lung disease (e.g., severe COPD, moderate or severe restrictive lung disease, diffuse interstitial fibrosis or alveolitis, pulmonary thromboembolism)
• Severe renal dysfunction with an estimated Glomerular Filtration Rate (eGFR) < 30 mL/min per 1.73 m2
• Severe hepatic impairment, e.g., Child Pugh Class C.
• Other protocol-defined inclusion/exclusion criteria may apply.