Intensive Uric Acid Lowering With Verinurad and Febuxostat in Patients With Albuminuria
- Conditions
- HyperuricemiaAlbuminuriaType 2 Diabetes
- Interventions
- Drug: Placebo
- Registration Number
- NCT03118739
- Lead Sponsor
- AstraZeneca
- Brief Summary
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).
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Verinurad 9 mg+Febuxostat 80 mg Verinurad 9 mg+Febuxostat 80 mg Capsule administered orally, once daily for 24 weeks Placebo Placebo Capsule administered orally, once daily for 24 weeks
- Primary Outcome Measures
Name Time Method Urinary Albumin to Creatinine Ratio (UACR) From Baseline to 24 Weeks of Treatment LS Mean Percentage Change (95% CI) from Baseline in UACR
Urinary Albumin to Creatinine Ratio (UACR) Compared to Placebo From Baseline to 24 Weeks of Treatment LS Mean Percentage Change (90% CI) from Baseline in UACR Compared to Placebo
- Secondary Outcome Measures
Name Time Method sUA From Baseline to 12 Weeks and 24 Weeks of Treatment LS Mean Percentage Change (95% CI) from Baseline in sUA
eGFR From Baseline to 12 Weeks and 24 Weeks of Treatment LS Mean Percentage Change (95% CI) from Baseline in eGFR
Serum Creatinine From Baseline to 12 Weeks and 24 Weeks of Treatment LS Mean Percentage Change (95% CI) from Baseline in Serum Creatinine
Serum Cystatin C From Baseline to 12 Weeks and 24 Weeks of Treatment LS Mean Percentage Change (95% CI) from Baseline in Serum Cystatin C
Serum High Sensitivity C-reactive Protein From Baseline to 12 Weeks and 24 Weeks of Treatment LS Mean Percentage Change (95% CI) from Baseline in Serum High Sensitivity C-reactive Protein
Clinical Assessments From Baseline to 12 Weeks and 24 Weeks of Treatment Change from Baseline in Diastolic and Systolic Blood Pressure
MRI Variables - LV Mass/End-diastolic Volume From Baseline to 24 Weeks of Treatment Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
MRI Variables - Kidney Cortex T2 Star - BOLD MRI From Baseline to 24 Weeks of Treatment Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
MRI Variables - LV End-diastolic Volume, LV End-systolic Volume, LV Stroke Volume From Baseline to 24 Weeks of Treatment Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial Strain From Baseline to 24 Weeks of Treatment Change from baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
MRI Variables - Diastolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate and Systolic Circumferential Strain Rate, Longitudinal Strain Rate, Radial Strain Rate From Baseline to 24 Weeks of Treatment Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
MRI Variables - LV Mass From Baseline to 24 Weeks of Treatment Change from Baseline in MRI Variables at Week 24 (CFB = Change from Baseline)
Trial Locations
- Locations (1)
Research Site
🇺🇸Webster, Texas, United States