The purpose of this clinical research study is to evaluate signals of potential clinical benefit of the combination of Verinurad and Febuxostat in lowering concentrations of circulating uric acid and thus improving kidney or cardiovascular status of patients with hyperuricemia, albuminuria, and Type 2 diabetes (T2DM).

Brief Title

Intensive Uric Acid Lowering With Verinurad and Febuxostat in Patients With Albuminuria

Official Title

Effects of Intensive Uric Acid Lowering Therapy With RDEA3170 (Verinurad) and Febuxostat in Patients With Albuminuria

Brief Summary

The purpose of this clinical research study is to evaluate signals of potential clinical<br /> benefit of the combination of Verinurad and Febuxostat in lowering concentrations of<br /> circulating uric acid and thus improving kidney or cardiovascular status of patients with<br /> hyperuricemia, albuminuria, and Type 2 diabetes (T2DM).

Detailed Description

Evidence shows independent associations between elevated serum uric acid (sUA) and the risk
of hypertension, myocardial infarction (MI), chronic kidney disease (CKD), T2DM, heart
failure (HF), and metabolic syndrome, including obesity. Gout is associated with an increased
risk of all-cause death, as well as cardiovascular death. The causal relationship between
elevated sUA, gout, and these disease outcomes remains to be proven.

Verinurad (RDEA3170), is a novel Urate Transporter 1 (URAT1) inhibitor in Phase II
development. Verinurad combined with the xanthine oxidase (XO) inhibitor febuxostat has been
shown to lower sUA in patients with recurrent gout in Phase II studies by >80%. The extensive
lowering of sUA delivered by the combination presents a unique opportunity to explore whether
intensive urate lowering therapy can improve kidney and/or cardiac health.

This study will assess if intensive serum urate lowering therapy, more potent than ever
explored before in the chronic out-patient setting, can improve chronic kidney or cardiac
function in the study population.

In order to maximize the scientific value of the study and minimize the risk for systemic
biases a parallel group, double blind, randomized design will be utilized.

The study will recruit patients with hyperuricemia and presenting with albuminuria.

Hyperuricemic patients are expected to benefit more from urate lowering, and albuminuria at
baseline is required, as the primary objective of the study will be to assess changes in
albuminuria.

Patients are also required to be diagnosed with T2DM. Patients with T2DM frequently exhibit
changes in cardiac function detectable using magnetic resonance imaging (MRI) that represents
an early, pre-symptomatic state of HF. By limiting recruitment to patients with T2DM and by
performing MRI at baseline and 6 months of therapy, the study will deliver insights into
whether or not intensive urate lowering therapy can positively affect not only chronic kidney
disease, but also cardiac disease.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.

Inclusion Criteria:

  -  Serum Uric Acid ≥6.0 mg/dL

  -  eGFR ≥30 mL/min/1.73 m2

  -  UACR between 30 mg/g and 3500 mg/g inclusive

  -  Diagnosed with T2DM

Exclusion Criteria:

  -  Treated with any drug for hyperuricemia in the 6 months preceding randomization.Drugs
     for hyperuricemia include all XO inhibitors (allopurinol, febuxostat and topiroxostat)
     and URAT1 inhibitors (lesinurad, verinurad, probenecid, and benzbromarone)

  -  Prior history of gout, unless prophylaxis therapy isn't required

  -  Patients who are pregnant, lactating, or planning to become pregnant

  -  Patients unsuitable or unable to undergo MRI assessment