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
Study type: Interventional
Phase: Phase 2

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.
    

Detailed description: 
      Evidence shows independent associations between hyperuricaemia and the risk of hypertension,
      myocardial infarction, chronic kidney disease (CKD), type 2 diabetes, heart failure, and
      metabolic syndrome, including obesity Furthermore, gout, an inflammatory arthritis caused by
      deposition of monosodium urate crystals in joints, is associated with an increased risk of
      all-cause death, as well as cardiovascular (CV) death.

      Hyperuricaemia is a prerequisite for development of gout, thus linking high levels of sUA to
      gout and to poor outcomes. However, the causal relationship between hyperuricaemia / gout and
      the aforementioned diseases and outcomes remains to be proven.

      Uric acid transporter 1 (URAT1) is responsible for reabsorption of uric acid (UA in the
      proximal tubule. Inhibition of URAT1 results in increased urinary excretion of UA.

      Verinurad (RDEA3170) is a novel URAT1 inhibitor in Phase 2 development for chronic kidney
      disease and heart failure.

      Verinurad combined with the xanthine oxidase (XO)inhibitor (XOI) febuxostat or allopurinol
      has been shown to lower sUA in patients with recurrent gout in Phase 2 studies by up to 80%..

      The primary objective of this study is to assess the effects of treatment with verinurad and
      allopurinol, allopurinol alone, and placebo on UACR at 6 months.

      In this study, change in UACR at 6 months of treatment is the primary endpoint for the
      efficacy evaluation of treatment with the combination of verinurad and allopurinol vs.
      placebo.

      A key secondary objective is evaluation of verinurad plus allopurinol on the reduction in
      UACR at 12 months.

      Further, standard safety parameters such as adverse event (AEs), serious adverse event
      (SAEs), and laboratory evaluations will be employed to assess the safety profile of the study
      drugs.

      Verinurad, allopurinol and oxypurinol plasma concentrations over time will also be measured.

      The study will recruit patients with Chronic Kidney Disease and Hyperuricaemia.
    

Intervention name(s): Verinurad; Allopurinol; Placebo for Verinurad; Placebo for Allopurinol
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 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
Other intervention name(s): Placebo; Placebo
Intervention MeSH terms: Allopurinol; Verinurad
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Chronic Kidney Disease