Inclusion Criteria:
- Male and female patients, age 40 to 85 years inclusive.
- • Patients with uncontrolled hypertension (here defined as having a mean daytime systolic BP ≥ 135 mmHg by ABPM at screening) despite treatment with a stable (at least 1 month) regimen that includes an optimal dose of an ARB plus a diuretic plus at least one additional class of anti-hypertensive medication.
For the purposes of this trial, optimal doses of anti-hypertensive medications are defined as:
- the highest dose listed in the clinical practice guideline from the American Society for Hypertension and the International Society for Hypertension or
- the highest allowable prescribed dose per the manufacturer's label or
- the highest dose tolerated by an individual patient or
- the highest dose appropriate for an individual patient in the judgment of the Investigator
- Subjects must weigh at least 45 kg to participate in the study and must have a body mass index (BMI) within the range of 18-38 kg/m^2.
Exclusion Criteria:
- Patients with an estimated GFR <60 ml/min/1.73m^2.
- Use of angiotensin converting enzyme inhibitors (ACE-inhibitors). Note: Patients who discontinue their ACE-inhibitor and substitute with an angiotensin receptor blocker may be eligible to be re-screened provided their anti-hypertensive regimen has been stable for at least 1 month. Any substitutions or changes to a patient's anti-hypertensive regimen should be done under the guidance of the patient's treating physician.
- Severe hypertension as defined by systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110 mmHg at screening.
- A history of secondary hypertension of any etiology including but not limited to unilateral or bilateral renal artery stenosis, polycystic kidney disease, coarctation of the aorta, primary hyperaldosteronism, Cushing's disease, pheochromocytoma, and drug-induced hypertension.
- Known current significant left ventricular outflow obstruction, such as obstructive hypertrophic cardiomyopathy or significant severe valvular disease on prior or current echocardiogram).
- A history of known moderate or malignant retinopathy defined as moderate (retinal signs of hemorrhage), microaneurysms, cotton-wool spots, hard exudates, or a combination thereof) or malignant (signs of moderate retinopathy plus swelling of the optic disk). Patients with a stable ophthalmologic history in the past 6 months are eligible.
- To facilitate ABPM assessment, an upper arm circumference greater than 42 cm.
- History within the previous 6 months of myocardial infarction, coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), hypertensive encephalopathy, stroke, or transient ischemic attack (TIA).
Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
• Women of child-bearing potential