A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Phase 3 Trial to Evaluate the Safety and Efficacy of Dapagliflozin in Subjects With Type 2 Diabetes With Inadequately Controlled Hypertension on an Angiotensin-Converting Enzyme (ACE) Inhibitor or Angiotensin Receptor Blocker (ARB) and an Additional Antihypertensive Medication
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 2,245
- 试验地点
- 155
- 主要终点
- Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure for 12 Week Double-Blind Treatment Period - Randomized Participants
研究概览
简要总结
The purpose of this study is to learn if BMS-512148 (Dapagliflozin), after 12 weeks, can improve (decrease) blood pressure in patients with type 2 diabetes with uncontrolled hypertension who are on an Angiotensin-converting enzyme inhibitor (ACEI) or an Angiotensin Receptor Blocker (ARB).The safety of this treatment will also be studied
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Males and females, 18 to 89 years old, with type 2 diabetes with inadequate glycemic control HbA1c between 7-10.5% and uncontrolled hypertension Systolic Blood Pressure (SBP) 140-165 and Diastolic Blood Pressure (DBP) 85-105
- •Subjects must have a mean 24 hr blood pressure ≥ 130/80 determined by Ambulatory Blood Pressure Monitoring (ABPM) within 1 week prior to Day 1 visit
- •Stable dose of oral antidiabetic agent (OAD) for at least 6 weeks [12 wks for Thiazolidinedione (TZD)] or a stable daily dose of insulin, as a monotherapy or in combination with another OAD, for 8 weeks, and a stable dose of ACEI or ARB and 1 additional antihypertensive medication for at least 4 weeks
- •C-peptide ≥ 0.8 ng/mL
- •Body Mass Index ≤ 45.0 kg/m2
- •Serum creatinine < 1.50 mg/dL for men or < 1.40 mg/dL for women
排除标准
- •Aspartate aminotransferase (AST) and /or Alanine aminotransferase (ALT) > 3.0*upper limit of normal (ULN)
- •Serum total bilirubin ≥ 1.5*ULN
- •Creatinine kinase > 3*ULN
- •Symptoms of severely uncontrolled diabetes
- •History of malignant or accelerated hypertension
- •Currently unstable or serious cardiovascular, renal, hepatic, hematological, oncological, endocrine, psychiatric, or rheumatic diseases
研究组 & 干预措施
Dapagliflozin 10 mg
Dapagliflozin 10 mg tablets
干预措施: Dapagliflozin (Drug)
Placebo matching Dapagliflozin
Placebo tablets matching dapagliflozin tablets
干预措施: Placebo matching Dapagliflozin (Drug)
结局指标
主要结局
Adjusted Mean Change From Baseline in Seated Systolic Blood Pressure for 12 Week Double-Blind Treatment Period - Randomized Participants
时间窗: Baseline to Week 12
Systolic blood pressure (SBP) was measured in millimeters of mercury (mmHg) on Day -1, Day 1, Weeks 2, 4, 8, and 12 of the Double Blind Period. Blood pressure (BP) values were obtained after the participant was seated for quietly for 10 minutes; a mean of 3 replicate measurements was taken at least 1 minute apart. However, if the 3 consecutive seated BP readings were not within 8 mm Hg of each other, an additional 2 BP readings were obtained (total = 5) and incorporated into the calculated mean. BP was measured in both arms. If the BP was higher in one arm than the other, then this arm was used; if no difference, the participant's dominant arm was used for all future BP measurements. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. Participants refrained from ingestion of caffeine, alcohol, or nicotine at least 10 hours prior to their visit and having their BP measured.
Adjusted Mean Change From Baseline in Hemoglobin A1c (HbA1c) for 12 Week Double-Blind Treatment Period - Randomized Participants
时间窗: Baseline to Week 12
Adjusted mean change in glycosylated hemoglobin ( HbA1c) from baseline at Week 12 was calculated. HbA1c was measured as percent of hemoglobin by a central laboratory. Baseline was defined as the last assessment prior to the start date and time of the first dose of the double-blind study medication. HbA1c values were obtained at enrollment and lead-in (Day -28) periods, and at Day 1, Weeks 4, 8, and 12, in the double-blind period.
次要结局
- Adjusted Mean Change From Baseline in 24-hour Ambulatory Systolic Blood Pressure at Week 12 Last Observation Carried Forward (LOCF)(Baseline, Week 12)
- Adjusted Mean Change From Baseline in Seated Diastolic Blood Pressure (DBP) for 12 Week Double-Blind Treatment Period - Randomized Participants(Baseline to Week 12)
- Adjusted Mean Change From Baseline in 24-hr Ambulatory Diastolic Blood Pressure at Week 12 (LOCF)(Baseline, Week 12)
- Adjusted Mean Change From Baseline in Serum Uric Acid at Week 12 in Double-Blind Treatment Period - Randomized Participants(Baseline, Week 12)
- Number of Participants With Deaths,Serious Adverse Events (SAEs), Adverse Events (AEs), Hypoglycemia Events, Discontinuation Due to AEs, SAEs and Hypoglycemia, During the 12 Week Double Blind Period, Including Data After Rescue(Baseline to last dose of 12 weeks of double blind medication plus 30 days if SAE or plus 4 days if AE/hypoglycemic event)
- Number of Participants With Marked Chemistry Laboratory Abnormalities in 12 Week Double Blind Treatment Period, Including Data After Rescue(Baseline (Day 1) to last dose double blind medication (Week 12) plus 4 days)
- Number of Participants With Elevated Liver Laboratory Tests in Participants Treated With Double Blind 10 mg Dapagliflozin or Placebo , Including Data After Rescue(Baseline (Day 1) to last dose double blind medication (Week 12) Plus 30 days)
- Number of Participants With Normal or Abnormal Electrocardiogram Summary Tracing at Week 12 (LOCF), Including Data After Rescue(Baseline, Week 12)
- Proportion of Participants With Orthostatic Hypotension at Baseline and Week 12, Including Data After Rescue(Baseline (Day 1), Week 12)