NCT03990363

A Study of Verinurad and Allopurinol in Patients With Chronic Kidney Disease and Hyperuricaemia

A Phase 2b, Multicentre, Randomised, Double-blind, Placebo-controlled Study of Verinurad and Allopurinol in Patients With Chronic KIdney Disease and Hyperuricaemia

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 861 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 130 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Chronic Kidney Disease

Interventions

Type	Name	Description
DRUG	Verinurad	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
DRUG	Allopurinol	Study treatments will be titrated in 3 steps: Low dose (100 mg), intermediate (200 mg) and High Dose ( 300 mg) Allopurinol
DRUG	Placebo for Verinurad	Matching Capsule
DRUG	Placebo for Allopurinol	Matching tablet

Timeline

• Start date: 2019-07-23
• Primary completion: 2021-11-22
• Completion: 2021-11-22
• First posted: 2019-06-19
• Last updated: 2023-03-02
• Results posted: 2023-03-02

Locations

165 sites across 12 countries: United States, Czechia, France, Hungary, Israel, Italy, Mexico, Poland, Romania, Slovakia, South Africa, Spain

Regulatory

• FDA-regulated drug study