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

AstraZeneca

Status and phase: Completed; Phase 3

Conditions: Type 2 Diabetes

Treatments: Drug: Placebo-matching dapagliflozin; Drug: Dapagliflozin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01137474

2010-019797-32 (EudraCT Number)

MB102-073 ST

Details and patient eligibility

About

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.

Enrollment: 2,996 patients

Sex: All

Ages: 18 to 89 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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2,996 participants in 4 patient groups, including a placebo group

Dapagliflozin, 10 mg

Experimental group

Description:

Oral tablets administered as 10 mg once daily for up to 12 weeks

Treatment:

Drug: Dapagliflozin

Placebo-matching dapagliflozin

Placebo Comparator group

Description:

Oral tablets administered once daily in the morning

Treatment:

Drug: Placebo-matching dapagliflozin

Dapagliflozin, 2. 5 mg

Experimental group

Description:

Oral tablets administered as 2.5 mg once daily for up to 12 weeks (Arm discontinued as of Protocol Amendment 8)

Treatment:

Drug: Dapagliflozin

Dapagliflozin, 5 mg

Experimental group

Description:

Oral tablets administered as 5 mg once daily for up to 12 weeks (Arm discontinued as of Protocol Amendment 8)

Treatment:

Drug: Dapagliflozin