NCT01496430终止3 期
A Randomized, Double-Blind, Phase 3b Proof-of-Concept Study to Evaluate the Efficacy and Safety of TAK-491 Compared to Placebo When Used in Combination With Metformin in Subjects With Hypertension and Type 2 Diabetes
Takeda0 个研究点目标入组 105 人开始时间: 2012年1月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 105
- 主要终点
- Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure
研究概览
简要总结
The purpose of this study was to evaluate the antihypertensive and antiglycemic effects, as well as the safety and tolerability of TAK-491 (azilsartan medoxomil), once daily (QD), in stage 1 hypertensive, type 2 diabetes mellitus (T2DM) participants whose glycemic control was inadequate on metformin alone.
详细描述
The study included a Screening Period of up to 4 weeks, which coincided with a 2-week single-blind, placebo Run-in Period, a 24 week Treatment Period, and a 2-week Follow-up Period. The duration of the study was approximately 30 weeks. The planned number of participants (n=450) was not reached; actual enrollment consisted of 105 particpants. Due to low enrollment this study was terminated early by Takeda.
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
- •Was male or female and ≥18 years.
- •Had type 2 diabetes mellitus with HbA1c of ≥7.5 to ≤9.5% at Screening.
- •Was treated with metformin alone (no treatment with any antidiabetic agents other than metformin within the 3 months prior to Screening) and was experiencing inadequate glycemic control. The participant should have received metformin monotherapy for ≥8 weeks prior to Screening at a stable dose ≥1500 mg). Participants with a maximum tolerated dose (MTD) that was documented to be less than 1500 mg of metformin could also be enrolled if this dose had been stable for 8 weeks prior to Screening.
- •Was treated with antihypertensive therapy and had a mean, trough, sitting clinic systolic blood pressure (SBP) ≥135 and < 160 mm Hg on Day -1 (after washout of prior antihypertensive therapy) or the participant had not received antihypertensive treatment within 28 days before Screening and had a mean sitting clinic SBP ≥135 and < 160 mm Hg at the Screening Visit and on Day -
- •Had clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or results that were deemed not clinically significant in this participant population for inclusion in this study, by the investigator.
排除标准
- •Had a mean, trough, sitting clinic diastolic blood pressure (DBP) ≥ 100 mm Hg at Day -
- •Had type 1 or poorly controlled type 2 diabetes mellitus (HbA1c >9.5%) at Screening.
- •Was taking or expected to take an excluded medication.
- •Had a history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack.
- •Had clinically significant cardiac conduction defects (for example, 3rd degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation).
- •Had hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease.
- •Had secondary hypertension of any etiology (e.g., renovascular disease, pheochromocytoma, Cushing's syndrome).
- •Had renal dysfunction defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 at Screening.
- •Had albuminuria defined as >200 mg/g at Screening.
- •Had known or suspected unilateral or bilateral renal artery stenosis.
- •Had unexplained microhematuria ≥3 RBCs/HPF or macrohematuria at Screening and confirmed on repeat testing.
- •Treatment with antidiabetic agents (sulfonylureas, glucagon-like peptide-1 (GLP-1) analogues, dipeptidyl peptidase-4 (DPP-4) inhibitors, glinides, thiazolidinediones (TZDs), and/or insulin) other than metformin during the 3 months prior to Screening.
- •Had hyperkalemia as defined by central laboratory normal reference range at Screening.
研究组 & 干预措施
Placebo QD
Placebo Comparator
Azilsartan medoxomil placebo-matching tablets, orally, once daily for up to 24 weeks.
干预措施: Placebo (Drug)
Azilsartan Medoxomil 40 mg QD
Experimental
Azilsartan medoxomil 40 mg, tablets, orally, once daily for up to 24 weeks.
干预措施: Azilsartan medoxomil (Drug)
Azilsartan Medoxomil 80 mg QD
Experimental
Azilsartan medoxomil 80 mg, tablets, orally, once daily for up to 24 weeks.
干预措施: Azilsartan medoxomil (Drug)
结局指标
主要结局
Change From Baseline in Trough Sitting Clinic Systolic Blood Pressure
时间窗: Baseline and Week 8
The change in trough systolic blood pressure measured at week 8 relative to baseline. The trough is the average of the non-missing values of the 3 serial trough sitting systolic blood pressure measurements.
次要结局
- Change From Baseline to Week 6 and Week 24 in 2h Glucose During Oral Glucose Tolerance Testing (OGTT)(Baseline and Weeks 6 and 24)
- Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring(Baseline and Week 8)
- Change From Baseline in the Trough (22 to 24 Hours After Dosing) Systolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring(Baseline and Week 8)
- Change From Baseline in Trough Sitting Clinic Diastolic Blood Pressure(Baseline and Week 8)
- Change From Baseline in the 24-hour Mean Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring(Baseline and Week 8)
- Change From Baseline in the Mean Daytime (6 AM to 10 PM) Diastolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring(Baseline and Week 8)
- Time to First Glycemic Rescue(24 Weeks)
- Change From Baseline in the 24-hour Mean Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring(Baseline and Week 8)
- Change From Baseline in the Mean Daytime (6 AM to 10 PM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring(Baseline and Week 8)
- Change From Baseline in the 12-hr Mean Diastolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring(Baseline and Week 8)
- Percentage of Participants Requiring Rescue Glycemic Therapy(24 Weeks)
- Change From Baseline in Glycosylated Hemoglobin (HbA1c)(Baseline and Week 24)
- Change From Baseline in the Mean Nighttime (12 AM to 6 AM) Systolic Blood Pressure, as Measured by Ambulatory Blood Pressure Monitoring(Baseline and Week 8)
- Change From Baseline to Week 6 and Week 24 in AUC for Insulin During OGTT(Baseline and Weeks 6 and 24)
- Change From Baseline to Week 6 and Week 24 in AUC for C-peptide During OGTT(Baseline and Weeks 6 and 24)
- Change From Baseline to Week 6 and Week 24 in AUC for Insulin/Glucose Ratio During OGTT(Baseline and Weeks 6 and 24)
- Change From Baseline to Week 6 and Week 24 in AUC for Glucagon During OGTT(Baseline and Weeks 6 and 24)
- Change From Baseline in the 12-hr Mean Systolic Blood Pressure Measured by Ambulatory Blood Pressure Monitoring(Baseline and Week 8)
- Change From Baseline in the Trough (22 to 24 Hours After Dosing) Diastolic Blood Pressure as Measured by Ambulatory Blood Pressure Monitoring(Baseline and Week 8)
- Change From Baseline in HbA1c(Baseline and Weeks 2, 4, 6, 8, 12, 16 and 20)
- Change From Baseline in Fasting Plasma Glucose(Baseline and Weeks 2, 4, 6, 8, 12, 16, 20, and 24)
- Change From Baseline to Week 6 and Week 24 in the Area Under the Plasma Concentration-time Curve (AUC) for Glucose During OGTT(Baseline and Weeks 6 and 24)
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