Study of Verinurad in Heart Failure With Preserved Ejection Fraction
Condition: Heart Failure With Preserved Ejection Fraction (HFpEF)
MeSH terms: Heart Failure
Intervention: Verinurad; Allopurinol; Placebo for verinurad; Placebo for allopurinol
Intervention description: The treatment will be titrated in 3 steps for target low dose (3 mg), intermediate dose (7.5 mg) and high dose (12mg) of verinurad.
Drug: Allopurinol The treatment will be titrated in 3 steps. Low dose (100mg), intermediate (200mg) and high dose (300mg) of allopurinol.; Study treatments will be titrated in 3 steps: Low dose (100mg), intermediate (200mg) and high dose (300mg) of allopurinol; Matching Capsule; Matching tablet
Intervention MeSH terms: Allopurinol; Verinurad
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 159.0
Sex: All
Minimum age: 40 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Phase 2,; Double-Blind,; Placebo and Active Control,; Verinurad,; Allopurinol,; HFpEF,; Heart Failure

Summary:

      International, Multicenter, Double-Blind, Placebo and Active Control Efficacy and Safety
      Study to Evaluate Verinurad combined with Allopurinol in Heart Failure with Preserved
      Ejection Fraction
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient must be ≥ 40 years of age at the time of signing the ICF

          -  Patients with hyperuricaemia defined as sUA level of > 6 mg/dL.

          -  Patients with documented diagnosis of symptomatic HFpEF according to all of the
             following criteria:

               1. Have NYHA functional class II-III at enrolment

               2. Have medical history of typical symptoms/signs of HF > 6 weeks before enrolment

               3. LVEF ≥ 45%

               4. NT-proBNP ≥ 125 pg/mL (≥ 14.75 pmol/L) at Visit 1 for patients without ongoing
                  atrial fibrillation/flutter.

          -  Patients able to exercise to near exhaustion during a CPET as exhibited by RER

             ≥ 1.05 during CPET conducted during screening. If patient does not achieve RER ≥ 1.05
             the CPET may be repeated once, at least 48 hours but less than 2 weeks (but before
             randomisation) after the initial test; in such cases the second test will serve as
             baseline.

          -  Male or female

        Exclusion Criteria:

          -  eGFR < 30ml/min/1.73m2 (based on CKD-EPI formula)

          -  Presence of any condition that precludes exercise testing

          -  Known history of a documented LVEF < 40%

          -  Probable alternative or concomitant diagnoses which in the opinion of the Investigator
             could account for the patient's HF symptoms and signs (eg, anaemia, hypothyroidism)

          -  Known carrier of the Human Leukocyte Antigen-B (HLA-B) *58:01 allele: HLA-B

             *58:01 genotyping is mandatory prior to randomization for all patients.

          -  Patients diagnosed with tumor lysis syndrome or Lesch-Nyhan syndrome

          -  Patients who are severely physically or mentally incapacitated and who in the opinion
             of investigator are unable to perform the patients' tasks associated with the protocol

          -  Presence of any condition which, in the opinion of the investigator, places the
             patient at undue risk or potentially jeopardises the quality of the data to be
             generated

          -  Current acute decompensated HF or hospitalisation due to decompensated HF < 4 weeks
             prior to enrolment

          -  Myocardial infarction, unstable angina, coronary revascularisation (percutaneous
             coronary intervention or coronary artery bypass grafting), ablation of atrial
             flutter/fibrillation, valve repair/replacement, implantation of a cardiac
             resynchronisation therapy device, stroke or transient ischemic attack within 6 months
             prior to enrolment.

          -  Planned coronary revascularisation, ablation of atrial flutter/fibrillation and/or
             valve repair/replacement

          -  Atrial fibrillation with persistent resting heart rate > 110 beats per minute.