An Open-label, Randomized, Parallel-group Study to Evaluate the Acute and Steady-state Renal Hemodynamic Responses to Aliskiren in Patients With Type 2 Diabetes Mellitus
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Novartis
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Aliskiren or Irbesartan
研究概览
简要总结
The study objective was to assess the effect of single and multiple doses of aliskiren on renal plasma flow, glomerular filtration rate and to compare the effects of single and multiple doses of aliskiren versus captopril or irbesartan on renal blood flow, glomerular filtration rate, and retinal blood flow in patients with type 2 diabetes mellitus.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hypertensive, male and females of non-child bearing potential patients, with type 2 diabetes mellitus (T2DM) (diagnosed at least 8 weeks before Screening), with or without renal impairment; estimated glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73 m^2, documented at least 3 months before the study start, aged 18-75 years with a minimum body weight of 50 kg and having an appropriate intravenous access as determined by the study staff, able to communicate well were enrolled in the study.
- •Patients must be on a stable dose of hypoglycemic medications for at least 8 weeks prior to the study.
- •Patients must be medically able to discontinue anti- hypertensive medications for the duration of the study.
排除标准
- •Patients with type 1 diabetes mellitus or uncontrolled T2DM (HbA1C> 11%), eGFR <40 mL/min/1.73 m^2 (calculated by the Modification of Diet in Renal Disease (MDRD) formula), renal disease not caused by diabetes or hypertension, serum potassium < 3.5 or > 5.1 mEq/L, heart failure (New York Heart Association (NYHA) Class II-IV) or history of acute/decompensated heart failure within the 6 months prior to dosing, history of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any percutaneous coronary intervention (PCI) during the 6 months prior to the baseline visit, history of malignancy including leukemia and lymphoma within past five years, hypertensive encephalopathy any time in the past or cerebrovascular accident within the 6 months prior to the baseline visit, or with history of drug or alcohol abuse within the 12 months prior to dosing were excluded from the study.
- •Patients with glaucoma, or prior ocular surgery.
- •Patients with renal disease not caused by diabetes or hypertension.
- •Patients with history of clinically significant drug or atopic allergy, acute or chronic respiratory disease, history of malignancy, or history of myocardial infarction, unstable angina pectoris, coronary bypass surgery, or any coronary intervention (percutaneous coronary intervention; PCI) during the 6 months prior to the study.
- •Patients who had used any prescription drugs which may affect the renin-angiotensin-aldosterone system or with known effect on renal hemodynamics within 2 weeks prior to dosing and during the study, over-the-counter (OTC) medication within two (2) weeks prior to dosing,
- •Any surgical or medical condition which may jeopardize the patient in case of participation in the study.
- •Participation in any clinical investigation within 4 weeks prior to the study.
- •Donation or loss of 400 mL or more of blood within 8 weeks prior to the study.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Aliskiren
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
干预措施: Aliskiren (Drug)
Aliskiren
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received aliskiren 300 mg tablets orally once a day for 14 days.
干预措施: Captopril (Drug)
Irbesartan
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
干预措施: Irbesartan (Drug)
Irbesartan
On Day 1 participants received a single oral dose of 25 mg captopril. Starting on Day 2 participants received irbesartan 300 mg tablets orally once a day for 14 days.
干预措施: Captopril (Drug)
结局指标
主要结局
Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Aliskiren or Irbesartan
时间窗: Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.
Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. The measure of the single dose effect (SDE) for aliskiren and irbesartan was calculated as Day 2 peak - Day 2 baseline RPF. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept.
Change From Baseline to Steady State Trough in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan
时间窗: Day 2 and Day 15 at Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) .
Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. This multiple dose effect at steady state (MDE_SS) was calculated as Day 15 baseline - Day 2 baseline. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values.
Change From Baseline to Steady State Peak in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan
时间窗: Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and Day 15: 1, 2, 3, 4 and 5 hours post-dose.
Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. This maximum multiple dose effect (MDE_Max) was calculated as Day 15 peak - Day 2 baseline. Baseline RPF was determined as the median of the -10 minute, -5 minute predose and predose (0 hour) values. Peak RPF was obtained using a moving average concept.
Change From Single Dose Peak to Steady State Peak in Renal Plasma Flow (RPF) After Aliskiren or Irbesartan
时间窗: Day 2 and Day 15: 1, 2, 3, 4 and 5 hours post-dose.
Renal plasma flow (RPF) was measured by the clearance of para-aminohippurate (PAH) by autoanalyzer methods. Accumulation of peak effect from single dose to multiple dose (MDE_Acc) was calculated as Day 15 peak - Day 2 peak. Peak RPF was obtained using a moving average concept.
次要结局
- Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Aliskiren or Irbesartan(Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.)
- Change From Baseline to Steady State Trough in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan(Day 2 and Day 15 at Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) .)
- Change From Baseline to Steady State Peak in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan(Day 2: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and Day 15: 1, 2, 3, 4 and 5 hours post-dose.)
- Change From Single Dose Peak to Steady State Peak in Glomerular Filtration Rate (GFR) After Aliskiren or Irbesartan(Day 2 and Day 15: 1, 2, 3, 4 and 5 hours post-dose.)
- Change in Plasma Renin Concentration (PRC) After Captopril, Aliskiren or Irbesartan(Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.)
- Change in Plasma Pro-renin Concentration After Captopril, Aliskiren or Irbesartan(Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.)
- Change in Plasma Renin Activity (PRA) After Captopril, Aliskiren or Irbesartan(Predose and 5 hours post dose on Days 1, 2 and 15.)
- Change in Plasma Angiotensin I After Captopril, Aliskiren or Irbesartan(Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.)
- Change From Baseline in Renal Plasma Flow (RPF) After a Single Dose of Captopril(Day 1: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.)
- Change From Baseline in Glomerular Filtration Rate (GFR) After a Single Dose of Captopril(Day 1: Baseline (10 minutes and 5 minutes pre-treatment and 0 hours) and 1, 2, 3, 4 and 5 hours post-dose.)
- Change in Plasma Angiotensin II After Captopril, Aliskiren or Irbesartan(Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.)
- Change in Serum Aldosterone After Captopril, Aliskiren or Irbesartan(Predose (Baseline) and 5 hours post dose on Days 1, 2 and 15.)
- Change From Baseline in Retinal Blood Flow After Aliskiren or Irbesartan(Baseline (Day 1), Day 2 and Day 15.)