A Study of Verinurad and Allopurinol in Patients With Chronic Kidney Disease and Hyperuricaemia
Condition: Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Hyperuricemia
Intervention: Verinurad; Allopurinol; Placebo for Verinurad; Placebo for Allopurinol
Intervention description: Study treatments will be titrated in 3 steps for target low dose (3 mg), intermediate dose ( 7.5 mg) and High Dose (12 mg) Verinurad.
As per Protocol Version 5.0, Patients from 3 mg dose will be switched to 24 mg at visit 9; Study treatments will be titrated in 3 steps: Low dose (100 mg), intermediate (200 mg) and High Dose ( 300 mg) 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: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 861.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Chronic Kidney Disease

Summary:

      The purpose of this clinical research study is to establish the dose of verinurad combined
      with allopurinol 300 mg once daily that will elicit the desired response; ie, reduction in
      urinary albumin to creatinine ratio (UACR) at 6 months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  The subject has given written informed consent prior to any mandatory study specific
             procedures, sampling, and analyses, and is able to understand and comply with all
             study procedures

          -  Adult Patient ≥18 years of age with CKD for >3 months.

          -  Patients with background standard of care treatment for albuminuria and/or T2DM and
             treated according to locally recognised guidelines. Therapy optimised and stable for
             ≥4 weeks before study entry and including an angiotensin-converting enzyme inhibitor
             or an angiotensin receptor blocker, unless justified.

          -  If treated with a sodium-glucose transport protein (SGLT2) inhibitor, stable dose for
             ≥4 weeks before randomisation.

          -  Meeting screening criteria for sUA and eGFR (Visit 2): sUA ≥6.0 mg/dL. ∙ eGFR ≥25
             mL/min/1.73 m2 Chronic Kidney Disease Epidemiology Collaboration

          -  UACR between 30 mg/g and 5000 mg/g.

          -  Female patients: Negative pregnancy test for childbearing potential. 1 year
             post-menopausal, surgically sterile, or using an acceptable method of contraception
             during the study and 4 weeks after the last dose of study treatment.

        Exclusion Criteria:

          -  Autosomal dominant or autosomal recessive polycystic kidney disease, lupus nephritis
             or anti-neutrophil cytoplasmic antibody associated vasculitis (granulomatosis with
             polyangiitis [Wegener's granulomatosis], microscopic polyangiitis, or eosinophilic
             granulomatosis with polyangiitis [Churg-Strauss syndrome]).

          -  History of renal transplantation

          -  Known carrier of the Human Leukocyte Antigen-B *58:01 allele.

          -  Patients diagnosed with tumor lysis syndrome or Lesch-Nyhan syndrome

          -  Patients who in the opinion of investigator are unable to perform the patients' tasks
             associated with the protocol or Presence of any condition which, places the patient at
             undue risk or potentially jeopardises the quality of the data to be generated

          -  History of stroke, myocardial infarction, percutaneous coronary intervention, coronary
             artery bypass graft in the past 6 months

          -  Uncontrolled hypertension presenting with systolic blood pressure >180 mm Hg and/or
             diastolic blood pressure >100 mm Hg

          -  Diagnosed with heart failure and New York Heart Association Functional Classification
             Class IV at the time of randomisation

          -  QT interval corrected by the Fridericia formula >470 msec; patients diagnosed with
             long QT syndrome; patients with a family history of long QT syndrome.

          -  Subjects with severe hepatic impairment, as judged by the investigator, of Child-Pugh
             Class C (decompensated cirrhosis), or with major cirrhosis complications (eg,
             hepatorenal syndrome)

          -  Receiving cytotoxic or immunosuppressive therapy or other immunotherapy for primary or
             secondary renal disease within 6 months prior to enrolment

          -  Treated with any drug for hyperuricaemia in the 6 months preceding randomisation.

          -  Dose of ACEi, ARBs, fenofibrate, guaifenesin, or SGLT2 inhibitors changed within 4
             weeks of randomisation or further dose titration expected after randomization