A Randomized, Crossover, Double Blind, Placebo Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Lorundrostat in Addition to Sodium-Glucose Cotransporter-2 Inhibitors, in Adults With Hypertension and Chronic Kidney Disease With Albuminuria
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 88
- 主要终点
- Placebo-adjusted change from baseline in automated office blood pressure (AOBP) systolic blood pressure (SBP) at Week 4
研究概览
简要总结
This is a randomized, double-blind (DB), placebo controlled, crossover study with a two-period, two-sequence (2x2) design evaluating the efficacy and safety of 25 mg QD lorundrostat (an aldosterone synthase inhibitor [ASI]) in addition to a SGLT2i for the treatment of hypertension in subjects with CKD and albuminuria while receiving stable treatment with an Angiotensin-converting enzyme inhibitor (ACEi) or an Angiotensin receptor blocker (ARB). Subjects will be at least 18 years old with hypertension, and mild to severe CKD with albuminuria at the Screening Visit.
详细描述
The study consists of up to a 2-week Screening period, a 2-week run-in period where subjects will either begin study provided dapagliflozin 10 mg or continue on their regularly prescribed SGLT2i, and two DB 4-week treatment periods separated by a 4-week washout period. Subjects will be randomized (1:1) to two treatment sequences: lorundrostat-placebo (LP) and placebo-lorundrostat (PL).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
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
- •Major Inclusion Criteria:
- •At Screening, UACR of 200-5000 mg/g, inclusive, in first morning urine void
- •At Screening, eGFRs of ≥30 mL/min/1.73 m2
- •At Screening, AOBP SBP of 135-180 mmHg, inclusive
- •On a stable treatment with an ACEi or ARB for at least 2 months prior to Screening
- •At Screening, body mass index (BMI) of >18 kg/m2
排除标准
- •Subjects with known hypersensitivity to lorundrostat or any of its respective excipients
- •Subjects with known hypersensitivity to dapagliflozin or any of its respective excipients (subjects beginning dapagliflozin only)
- •At Screening, serum potassium >5.0 mmol/L
- •History of clinically significant hyponatremia within 1 year prior to Screening
- •Use of epithelial sodium channel (ENaC) inhibitors or Mineralocorticoid receptor antagonist (MRAs), including, but not limited to amiloride, triamterene, spironolactone, eplerenone, finerenone, from 4 weeks prior to the Screening Visit and during study participation. With the exception of MRAs in primary aldosteronism
- •Medical history of kidney disease related to autoimmune diseases (lupus, anti-neutrophil cytoplasmic antibody [ANCA] vasculitis), multiple myeloma or other known paraproteins, infiltrative diseases of the kidney, obstructive nephropathy, cystic kidney diseases, and renal transplantation
- •Medical history of advanced liver disease, including cirrhosis
- •Medical history of active autoimmune disease or recent (within 30 days) or anticipated need for immunosuppressive therapy
- •Diabetes mellitus with a glycosylated hemoglobin (HbA1c) >10% (>86 mmol/mol) at Screening
研究组 & 干预措施
Cohort 2
干预措施: Placebo QD + SGLT2i QD, Washout, Lorundrostat 25mg+SGLT2i QD (Drug)
Cohort 1
干预措施: Lorundrostat 25mg+SGLT2i QD, Washout, Placebo+SGLT2i QD (Drug)
结局指标
主要结局
Placebo-adjusted change from baseline in automated office blood pressure (AOBP) systolic blood pressure (SBP) at Week 4
时间窗: baseline to Week 4
Incidence and severity of adverse events (AEs)
时间窗: baseline to Week 14
次要结局
未报告次要终点