A Phase IIb, Multicenter, Randomised, Double-Blind, Dose-finding Study to Evaluate the Efficacy, Safety and Tolerability of Balcinrenone in Combination With Dapagliflozin Compared With Dapagliflozin in Patients With Chronic Kidney Disease and Albuminuria
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 324
- 试验地点
- 92
- 主要终点
- Relative Change in Urine Albumin-to-Creatinine Ratio (UACR) From Baseline to Week 12
研究概览
简要总结
The purpose of the study is to evaluate the efficacy, safety and tolerability of balcinrenone/dapagliflozin compared with dapagliflozin alone on patients with chronic kidney disease (CKD) and albuminuria. This study will evaluate the effect of the balcinrenone/dapagliflozin on urinary albumin-to-creatinine ratio (UACR), compared with dapagliflozin in patients with CKD. This is a dose-finding study aiming to identify an optimal dose of balcinrenone/dapagliflozin for a future Phase III study in patients with CKD.
详细描述
This is a Phase IIb, multicentre, randomised, double-blind, dose-finding, parallel group, double-dummy study aiming to determine the effect on albuminuria, as well as safety and tolerability, of balcinrenone/dapagliflozin compared with dapagliflozin, when given once daily on top of other Standard of Care (SoC) to patients with CKD and albuminuria.
Study population will include participants with CKD (eGFR ≥ 25 to < 60 mL/min/1.73 m2) and UACR > 100 mg/g to ≤ 5000 mg/g. Participants with or without a diagnosis of T2DM and with or without an SGLT2 inhibitor treatment at screening are eligible for the study.
The study will be conducted at approximately 110 sites in approximately 16 countries globally.
At least 300 participants will be randomised in order to have 300 evaluable participants.
Participants will be randomised to one of 3 treatment arms in a 1:1:1 ratio:
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)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years old - Diagnosis of CKD and eGFR ≥ 25 to < 60 mL/min/1.73 m
- •UACR > 100 mg/g (10 mg/mmol) to ≤ 5000 mg/g (500 mg/mmol). - Serum potassium ≥ 3.5 mmol/L to ≤ 5.0 mmol/L. - Stable RAAS inhibitors treatment for 4 weeks before screening. Participants who cannot tolerate or are not treated with RAAS inhibitors can also participate in the study.
排除标准
- •Uncontrolled arterial hypertension (SBP > 160 mmHg or DBP > 100 mmHg). - Hypotension defined as SBP < 100 mmHg. - Autosomal dominant polycystic kidney disease, lupus nephritis or ANCA-associated vasculitis or other nephropathies that are unstable or progress rapidly. - Cytotoxic or immunomodulatory therapy within 6 months prior to screening, or current, or planned within 6 months following randomization. - History of solid organ or bone marrow transplantation - Recent (90 d prior to screening) or ongoing dialysis, or likely need for dialysis within 3 months following randomization. - Myocardial infarction, acute coronary syndrome, stroke or transient ischaemic attack within the previous 12 weeks. - Type 1 diabetes mellitus (DM) or uncontrolled type 2 DM. - Hepatic disease, including active hepatitis, and/or hepatic impairment (Child-Pugh class B-C; or any of AST or ALT > 3 × ULN; or TBL > 2 × ULN. - Serum HCO3 < 18 mmol/L at screening. - Adrenal insufficiency (eg, Addison's disease, prolonged use of glucocorticoids). - Any use of the following within 4 weeks prior to screening: - MRA (or planned initiation of MRA treatment), potassium sparing diuretic, potassium binders, fludrocortisone. - Strong or moderate CYP3A4 inducers or inhibitors prohibited at least 1 week prior to randomisation and during treatment.
研究组 & 干预措施
Dapagliflozin 10 mg
Patients will be randomized 1:1:1 to either balcinrenone/dapagliflozin and matching placebo for dapagliflozin or dapagliflozin and matching placebo for balcinrenone/dapagliflozin
干预措施: Dapagliflozin 10 mg and matching placebo for balcinrenone/dapa gliflozin (Drug)
Balcinrenone/dapagliflozin 15 mg/10 mg
Patients will be randomized 1:1:1 to either balcinrenone/dapagliflozin and matching placebo for dapagliflozin or dapagliflozin and matching placebo for balcinrenone/dapagliflozin
干预措施: Balcinrenone/dapagliflozin 15 mg/10 mg and matching placebo for dapagliflozin 10 mg (Drug)
Balcinrenone/dapagliflozin 40 mg/10 mg
Patients will be randomized 1:1:1 to either balcinrenone/dapagliflozin and matching placebo for dapagliflozin or dapagliflozin and matching placebo for balcinrenone/dapagliflozin
干预措施: Balcinrenone/dapagliflozin 40 mg/10 mg and matching placebo for dapagliflozin 10 mg (Drug)
结局指标
主要结局
Relative Change in Urine Albumin-to-Creatinine Ratio (UACR) From Baseline to Week 12
时间窗: Baseline (Day 1) until Week 12 (Day 85)
Evaluating the effect of balcinrenone/dapagliflozin compared with dapagliflozin alone on Urine Albumin-to-Creatinine Ratio (UACR).
次要结局
未报告次要终点