A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study Evaluating the Safety and Efficacy of Oral GKT137831 in Patients With Type 2 Diabetes and Albuminuria
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 136
- 试验地点
- 48
- 主要终点
- Albuminuria Absolute Value and Ratio to Baseline by Study Visit and Treatment Group
研究概览
简要总结
NADPH oxidase enzymes (NOX) have been implicated in the development of several diabetic complications including diabetic nephropathy. GKT137831 is the first in class NOX1/4 inhibitor.
The primary objective of this study is to evaluate the efficacy of oral GKT137831 in patients with residual albuminuria despite maximal inhibition of the renin angiotensin aldosterone system.
详细描述
A double-blind, placebo-controlled, randomized, multicenter, parallel group Phase 2 study assessing a 12-week period of treatment with oral GKT137831 administered in addition to standard of care for patients with type 2 diabetes.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged 18 to 80 years
- •History of type 2 diabetes, defined as fasting plasma glucose ≥7.0 mmol/L (126 mg/dL) or a glycated hemoglobin (HbA1c) >6.5% (48 mmol/mol) on at least 2 occasions prior to screening.
- •Albuminuria defined as a UACR of 300 to 3500 mg/g.
- •An eGFR ≥30 mL/min/1.73 m2, as calculated by the CKD-EPI formula.
- •Must be taking an ACEI or an ARB for at least 6 weeks prior to the first screening visit (Visit 1) and during the screening period. The dose must have been stable for at least 4 weeks prior to the first screening visit (Visit 1). Combination therapy associating an ACEI and an ARB is not permitted.
排除标准
- •History of type 1 diabetes
- •Any other non-diabetic kidney disease(s) except for hypertensive nephropathy which is acceptable.
- •Diagnostic or interventional procedure requiring a contrast agent within 4 weeks of the first screening visit (Visit 1) or planned during the study.
- •History of renal transplant or planned renal transplant during the study.
- •A history of acute renal dialysis or acute kidney injury (defined according to the Kidney Disease: Improving Global Outcomes [KDIGO] definition) within 12 weeks of the first screening visit (Visit 1)
- •HbA1c level >11% (97 mmol/mol).
- •History of hypothyroidism requiring hormone replacement therapy.
- •History of active cardiovascular disease
- •A personal or family history of long QT syndrome.
- •Administration of any investigational product within 30 days or within 5 half-lives of the investigational agent
研究组 & 干预措施
GKT137831
GKT137831 100 mg capsules twice a day
干预措施: GKT137831 (Drug)
Placebo
Placebo capsule twice a day
干预措施: Placebo (Drug)
结局指标
主要结局
Albuminuria Absolute Value and Ratio to Baseline by Study Visit and Treatment Group
时间窗: Visit 4 (week -2) to visit 11 (week 12)
UACR from baseline to Visits 9, 10, and 11 (i.e. weeks 8, 10 and 12 of the treatment period, respectively). Baseline for UACR is defined as the geometric mean of the geometric means of the UACR values measured on Day-14 (visit 4) and Day 1 (visit 5). End of treatment is defined as the geometric mean of the geometric means of the UACR values measured at week 8 (visit 9), week 10 (visit 10) and week 12 (visit 11).
次要结局
- Glucose Metabolism by Homeostatic Model Assessment (HOMA)(Visits 5 (week 0), 8 (week 6), and 11 (week 12))
- Glucose Metabolism HbA1c(Visit 5 (week 0), 8 (week 6) and 11 (week 12))
- 24 Hours Albumin Excretion(Visits 5 (week 0) and 11 (week 12))
- 24 Hours Urine UACR(Visits 5 (week 0) and 11 (week 12))
- eGFR Change by Study Visit(Visits 5 (week 0), 6 (week 2), 7 (week 4), 8 (week 6), 9 (week 8), 10 (week 10), 11 (week 12), follow up (week 16))