A Study of the Effect of IW-1973 on the Exercise Capacity of Patients With Heart Failure With Preserved Ejection Fraction (HFpEF)

Inclusion criteria

• Patient is an ambulatory male or female ≥45 years old at the Screening Visit
• Patient has heart failure with ejection fraction (EF) of ≥40%
• Patient has a peak VO2 measuring <80% of age- and sex-adjusted normal values
• Patient has evidence in medical history supporting clinical heart failure syndrome consisting of at least 1 of the following:

• Hospitalization or emergency department visit for heart failure within the past year
• Elevated B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic peptide (NT-proBNP) within the past 6 months
• Echocardiographic evidence within the past 12 months of at least 2 of the following: left ventricular (LV) hypertrophy, left atrial (LA) enlargement, or diastolic dysfunction
• Hemodynamic evidence of elevated filling pressures
• Patient meets at least 2 of the following criteria at the Screening Visit:

• Diagnosis of type 2 diabetes mellitus or prediabetes
• History of hypertension
• Body mass index (BMI) >30 kg/m2
• Age ≥70 years

Exclusion criteria

• Patient has had acute coronary syndrome or percutaneous coronary intervention within 30 days before Randomization
• Patient has had cardiac transplantation or has cardiac transplantation planned during the study
• Patient has had cardiac artery bypass graft, cardiac mechanical support implantation, or other cardiac surgery in the 3 months before the Screening Visit or planned during the study
• Patient has severe chronic obstructive coronary disease as defined by chronic oxygen dependence
• Patient had had heart failure hospitalization with discharge within 30 days before the Screening Visit
• Patient has a history of clinically significant hypersensitivity or allergies to any of the inactive ingredients contained in the active or placebo drug products
• Patient has previously received IW-1973 in a study, or received an investigational drug during the 30 days or 5 half lives of that investigational drug (whichever is longer) before the Screening Visit, or is planning to receive another investigational drug at any time during the study
• Patient is taking specific inhibitors of phosphodiesterase 5 (PDE5), nonspecific inhibitors of PDE5, any supplements for the treatment of erectile dysfunction, riociguat, or nitrates or nitric oxide (NO) donors in any form
• Patient is taking strong cytochrome P450 3A (CYP3A) inhibitors
• Women of childbearing potential must have a negative pregnancy test prior to randomization and must agree to use protocol-specified contraception from the Screening Visit through 60 days after the final dose of study drug
• Male patients must be surgically sterile by vasectomy (conducted ≥60 days before the Screening Visit or confirmed via sperm analysis) or must agree to use protocol-specified contraception from the Screening Visit through 60 days after the final dose of study drug
• Other exclusion criteria per protocol