Effects of Intensive Uric Acid Lowering Therapy With RDEA3170 (Verinurad) and Febuxostat in Patients With Albuminuria
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Urinary Albumin to Creatinine Ratio (UACR)
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Verinurad capsules/matching placebo capsules and febuxostat/matching placebo capsules with randomization code printed on each label
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Verinurad 9 mg+Febuxostat 80 mg
Capsule administered orally, once daily for 24 weeks
干预措施: Verinurad 9 mg+Febuxostat 80 mg (Drug)
Placebo
Capsule administered orally, once daily for 24 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Urinary Albumin to Creatinine Ratio (UACR)
时间窗: 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
时间窗: From Baseline to 24 Weeks of Treatment
LS Mean Percentage Change (90% CI) from Baseline in UACR Compared to Placebo
次要结局
- sUA(From Baseline to 12 Weeks and 24 Weeks of Treatment)
- eGFR(From Baseline to 12 Weeks and 24 Weeks of Treatment)
- Serum Creatinine(From Baseline to 12 Weeks and 24 Weeks of Treatment)
- Serum Cystatin C(From Baseline to 12 Weeks and 24 Weeks of Treatment)
- Serum High Sensitivity C-reactive Protein(From Baseline to 12 Weeks and 24 Weeks of Treatment)
- Clinical Assessments(From Baseline to 12 Weeks and 24 Weeks of Treatment)
- MRI Variables - LV Mass/End-diastolic Volume(From Baseline to 24 Weeks of Treatment)
- MRI Variables - Kidney Cortex T2 Star - BOLD MRI(From Baseline to 24 Weeks of Treatment)
- MRI Variables - LV End-diastolic Volume, LV End-systolic Volume, LV Stroke Volume(From Baseline to 24 Weeks of Treatment)
- MRI Variables - LV Ejection Fraction, Circumferential Strain, Longitudinal Strain, Radial Strain(From Baseline to 24 Weeks of Treatment)
- 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)
- MRI Variables - LV Mass(From Baseline to 24 Weeks of Treatment)