Clinical Trials

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.