A Study of the Effect of IW-1973 on the Exercise Capacity of Patients With Heart Failure With Preserved Ejection Fraction (HFpEF)
Condition: Heart Failure With Preserved Ejection Fraction
MeSH terms: Heart Failure
Intervention: IW-1973; Placebo Oral Tablet
Intervention description: Oral Tablet; Oral Tablet
Intervention MeSH terms: Praliciguat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 196.0
Sex: All
Minimum age: 45 Years
Healthy volunteers: No
Keywords: Heart Failure; Cardiovascular; HF; HFpEF

Summary:

      The objective of the CAPACITY-HFpEF study is to evaluate the safety and efficacy of IW-1973
      compared with placebo when administered daily for approximately 12 weeks to patients with
      HFpEF. The study will evaluate the effect of oral IW-1973 on peak exercise capacity in
      patients with HFpEF, with or without permanent or persistent atrial fibrillation.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient is an ambulatory male or female ≥45 years old at the Screening Visit

          2. Patient has heart failure with ejection fraction (EF) of ≥40%

          3. Patient has a peak VO2 measuring <80% of age- and sex-adjusted normal values

          4. Patient has evidence in medical history supporting clinical heart failure syndrome
             consisting of at least 1 of the following:

               1. Hospitalization or emergency department visit for heart failure within the past
                  year

               2. Elevated B-type natriuretic peptide (BNP) or N-terminal pro b-type natriuretic
                  peptide (NT-proBNP) within the past 6 months

               3. 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

               4. Hemodynamic evidence of elevated filling pressures

          5. Patient meets at least 2 of the following criteria at the Screening Visit:

               1. Diagnosis of type 2 diabetes mellitus or prediabetes

               2. History of hypertension

               3. Body mass index (BMI) >30 kg/m2

               4. Age ≥70 years

        Exclusion Criteria:

          1. Patient has had acute coronary syndrome or percutaneous coronary intervention within
             30 days before Randomization

          2. Patient has had cardiac transplantation or has cardiac transplantation planned during
             the study

          3. 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

          4. Patient has severe chronic obstructive coronary disease as defined by chronic oxygen
             dependence

          5. Patient had had heart failure hospitalization with discharge within 30 days before the
             Screening Visit

          6. Patient has a history of clinically significant hypersensitivity or allergies to any
             of the inactive ingredients contained in the active or placebo drug products

          7. 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

          8. 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

          9. Patient is taking strong cytochrome P450 3A (CYP3A) inhibitors

         10. 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

         11. 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

         12. Other exclusion criteria per protocol