A Study of BMS-512148 (Dapagliflozin) in Patients With Type 2 Diabetes and Inadequately Controlled Hypertension on an Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker
Condition: Type 2 Diabetes
MeSH terms: Hypertension; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Dapagliflozin; Placebo-matching dapagliflozin
Intervention description: Oral tablets administered as 2.5, 5, or 10 mg, once daily for up to 12 weeks; Oral tablets administered as 0 mg once daily for up to 12 weeks
Intervention MeSH terms: Dapagliflozin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 2996.0
Sex: All
Minimum age: 18 Years
Maximum age: 89 Years
Healthy volunteers: No
Keywords: Diabetes Mellitus, Type 2; Diabetes Mellitus; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Hypoglycemic Agents; Pharmacologic Actions; Physiological Effects of Drugs

Summary:

      The purpose of this study is to learn whether 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 or an angiotensin receptor blocker. The
      safety of this treatment will also be studied.
    

Eligibility criteria:

        Key inclusion criteria

          -  Participants willing and able to give signed and written informed consent

          -  Males and females, aged 18 to 89 years, who have type 2 diabetes with inadequate
             glycemic control (hemoglobin A1c between 7% and 10.5%) and uncontrolled hypertension
             (seated systolic blood pressure of 140 to 165 mm Hg and seated diastolic blood
             pressure 85 to 105 mm Hg)

          -  Mean 24-hour BP>=130/80 mmHg determined by ABPM

          -  Stable dose of oral antidiabetic agent (OAD) for at least 6 weeks (12 weeks for
             thiazolidinedione) or a stable daily dose of insulin as monotherapy or in combination
             with another OAD, for 8 weeks, and a stable dose of an angiotensin-converting enzyme
             inhibitor or angiotensin-receptor blocker for at least 4 weeks

          -  C-peptide level ≥0.8 ng/mL

          -  Body mass index ≤ 45.0 kg/m^2

        Key exclusion criteria

          -  Aspartate aminotransferase or alanine aminotransferase level >3*upper limit of normal
             (ULN)

          -  Serum total bilirubin level >1.5*ULN

          -  Serum creatinine ≥2.0 mg/dL unless subject was on metformin, where exclusionary limits
             were serum creatinine ≥1.50 mg/dL for men and ≥1.40 mg/dL for women

          -  Estimated creatinine clearance of <60 mL/min

          -  Hemoglobin ≤10.0 g/dL for men and ≤9.0 g/dL for women

          -  Creatine kinase >3*ULN

          -  Positive for hepatitis B surface antigen

          -  Positive for antihepatitis C virus antibody

          -  Abnormal free T4 value

          -  History of diabetes insipidus

          -  Symptoms of poorly controlled diabetes that would preclude participation in this
             trial, including but not limited to, marked polyuria and polydipsia with greater than
             10% weight loss during the 3 months prior to enrollment.

          -  History of diabetic ketoacidosis or hyperosmolar nonketotic coma

          -  History of malignant and accelerated hypertension

          -  Known or suspected secondary hypertension

          -  Any of the following within 6 months of enrollment visit:

               -  Myocardial infarction

               -  Cardiac surgery or revascularization (coronary artery bypass surgery
                  /percutaneous transluminal coronary angioplasty)

               -  Unstable angina

               -  Unstable congestive heart disease or New York Heart Association Class III or IV

               -  Transient ischemic attack or significant cerebrovascular disease

               -  Unstable or previously undiagnosed arrhythmia