DORADO - Fixed Doses of Darusentan as Compared to Placebo in Resistant Hypertension

Inclusion Criteria:

• Subjects who are competent to provide written consent

• Aged 35 to 80 years

• Subjects with diabetes and/or chronic kidney disease must have a mean systolic bloodpressure ≥130 mmHg

• All other subjects must have a mean systolic blood pressure ≥140 mmHg

• Receiving and adhering to full doses of appropriate guideline-recommendedantihypertensive drugs from three different classes of antihypertensive agents,including a diuretic

• Female subjects of non-childbearing potential (i.e., post-menopausal for at lest 2years; surgically sterile)

Exclusion Criteria:

• Average sitting systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥110mmHg

• Serum ALT or AST >2 x the upper limit of the normal range (ULN)

• Subjects who have experienced myocardial infarction, unstable angina pectoris, or acerebrovascular accident (CVA) within 6 month; or sick sinus syndrome or second orthird degree atrioventricular block, atrial fibrillation or recurrent atrialtachyarrhythmia, recurrent ventricular tachycardia, or symptomatic bradycardia

• Implanted pacemakers or implanted cardioverter defibrillator (ICD)

• Symptomatic congestive heart failure requiring treatment

• Hemodynamically significant valvular heart disease

• Type I diabetes mellitus

• Hemodialysis or peritoneal dialysis; or history of renal transplant

• Diagnosis or recurrence of malignancy within the past 3 years

• Sleep apnea, unless a recent sleep study demonstrates arterial oxygen saturationgreater than or equal to 90%

• Subjects who perform alternating shift or night work

• Subjects who have participated in a clinical study involving another investigationaldrug or device within 4 weeks prior to Screening