RADAR: Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With AtRasentan - A Phase 2b, Prospective, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Safety and Efficacy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 149
- 试验地点
- 72
- 主要终点
- Change from baseline to Week 12 in Urinary Albumin to Creatinine Ratio (UACR)
研究概览
简要总结
Prospective, Randomized, Double-Blind, Placebo-Controlled Multicenter Study. The objective of the study is to evaluate the efficacy and safety of once daily administration of atrasentan tablets (low dose and high dose) compared to placebo in reducing residual albuminuria in Type 2 diabetic patients with nephropathy who are treated with the maximum tolerated labeled dose of a Renin Angiotensin System (RAS) inhibitor. If the patient is already receiving a maximum tolerated labeled daily dose of RAS inhibitor and a diuretic, he/she will complete 4 weeks of the Run-in Period on a dose that has not been adjusted. If the patient is currently not receiving a maximum labeled daily dose of a RAS inhibitor then the dose will be titrated up to the maximum tolerated labeled dose over the course of 4 to 8 weeks during the Run-in Period. It is expected that subjects not receiving a diuretic will have a diuretic added or titrated during this period to maximize RAS inhibition. Following titration to the maximum tolerated labeled dose, the patient will complete an additional 4 weeks of Run-In Period on an unchanged doses of RAS inhibitor and diuretics, unless medically contraindicated. The randomization will be stratified based on country where subjects are enrolled into the study, and the Week -1 Urinary Albumin to Creatinine Ratio (UACR) levels (< or = 1000 mg/g [113 mg/mmol], or > 1000 mg/g [113 mg/mmol]). Within each stratum, subjects will be randomly assigned in a 1:2:2 ratio to one of the following blinded treatment groups: Group A - Placebo once daily (QD) Group B - low dose atrasentan QD Group C - high dose atrasentan QD After the 12 weeks of study drug treatment, subjects will be followed up to 30 days.
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
- •Patient is > or = 18 years old.
- •Patient has Type 2 diabetes and has been treated with at least one anti hyperglycemic medication within the 12 months prior to the Screening Period.
- •Patient is currently receiving an angiotensin converting enzyme inhibitor (ACEi) or Angiotensin II receptor blocker (ARB) (Renin Angiotensin System (RAS) inhibitor).
- •For entry in the Run-in Period the patient must satisfy the following criteria based on the Screening laboratory values:
- •Estimated glomerular filtration rate (eGFR) ≥ 30 and ≤ 75 mL/min/1.73m2 by Epidemiology Collaboration (EPI) formula
- •Urinary Albumin to Creatinine Ratio (UACR) > or = 300 and < or = 3500 mg/g as determined by the geometric mean of the two morning void urine specimens obtained at the Screening visit (UACR > or = 34 mg/mmol and < or = 396 mg/mmol)
- •Serum albumin > or = 3.0 g/dL (30 g/L) - B-type Natriuretic Peptide (BNP) < or = 200 pg/mL (57.8 pmol/L) * Negative serum pregnancy test for female patients
- •Systolic Blood Pressure (SBP) > or = 110 mmHg and < or = 180 mmHg
- •Glucosylated hemoglobin A1c (HbA1c) < or = 12%
- •For entry in the Treatment Period the patient must satisfy the following criteria based on the last visit of the Run-in Period laboratory values:
- •Renin Angiotensin System (RAS) inhibitor at maximum tolerated labeled dose for the previous 4 weeks with no adjustments of dose
- •Diuretic at any dose unless medically contraindicated (with the exception of loop diuretics > or = 120 mg QD of furosemide or > or = 3.0 mg QD of bumetanide or > or = 150 mg QD of ethacrynic acid or > or = 60 mg QD of torasemide)
- •Urinary Albumin to Creatinine Ratio (UACR) > or = 200 and < or = 3500 mg/g as determined by the median of the three morning void urine specimens obtained prior to the Week -1 visit (UACR > or = 23 mg/mmol and < or = 396 mg/mmol)
- •Systolic blood pressure (SBP) > or = 110 mmHg and < or = 160 mmHg
- •Serum Potassium < or = 5.5 mEq/L (5.5 mmol/L)
- •Negative serum pregnancy test for female patients
排除标准
- •Patient has a history of moderate or severe edema, facial edema unrelated to trauma, or a history of myxedema in the prior 6 months to Screening.
- •Patient is receiving loop diuretics > or = 120 mg QD of furosemide or > or = 3.0 mg QD of bumetanide or > or = 150 mg QD of ethacrynic acid or > or = 60 mg QD of torasemide.
- •Patient has a history of pulmonary edema.
- •Patient has a history of pulmonary hypertension, or any lung diseases requiring oxygen therapy (i.e., chronic obstructive pulmonary disease, emphysema, pulmonary fibrosis).
- •Patient has a history of orthostatic hypotension within the past 6 months as defined by the presence of a supine-to-standing blood pressure decrease > or = 20 mmHg systolic or > or = 10 mmHg diastolic within 3 minutes of standing.
研究组 & 干预措施
Group A - Placebo QD
干预措施: Placebo (Drug)
Group B - Low dose Atrasentan QD
干预措施: Atrasentan (Drug)
Group C - High dose Atrasentan QD
干预措施: Atrasentan (Drug)
结局指标
主要结局
Change from baseline to Week 12 in Urinary Albumin to Creatinine Ratio (UACR)
时间窗: Every two weeks for 12 weeks
次要结局
- Differences in change from baseline to each post baseline measure for estimated glomerular filtration rate (eGFR)(Every two weeks for 12 weeks)
- Differences in change from baseline to each post baseline measure for EQ-5D Index Score(Once a month for 3 months)
- Differences in change from baseline to each post baseline measure for each of the Kidney Disease Quality of Life (KDQOL) Kidney Disease Targeted Scales(Once a month for 3 months)