The purpose of this study is to evaluate the safety and efficacy of ALT-711 in the treatment of isolated systolic hypertension in a formal dose-ranging study in patients without left ventricular hypertrophy. Eligible patients will be randomized to double-blind treatment once daily for 6 months with oral ALT-711 (35, 70, 140, or 210 mg) or placebo.

Inclusion Criteria

• Men or women at least 50 years of age.
• Screening diagnosis of isolated systolic hypertension, defined as systolic blood pressure >150 mm Hg and diastolic blood pressure <90 mm Hg (office blood pressure measurements) and systolic blood pressure >140 mm Hg (measured by 24-hour ambulatory blood pressure monitoring-mean daytime values).
• Baseline systolic blood pressure >150 mm Hg and diastolic blood pressure <90 mm Hg (office blood pressure measurements).
• Patients without left ventricular hypertrophy (LVH) as determined by limited echocardiography for LVH (i.e., wall thickness < 1.2 cm).
• Patient can complete an informed consent.

Exclusion Criteria

• Patient <50 years of age.
• Patients on antihypertensive therapy with changes in dose in the last 1 month prior to the entry into the study.
• Hb A1c > 9%.
• Serum creatinine > 1.7mg/dL.
• History of ketoacidosis or uncontrolled diabetes within the last 2 years.
• History of congestive heart failure.
• History of stroke, or any sequelae of a transient ischemic attack, reversible ischemic neurologic defect, or stroke, within the last 12 months.
• History of acute myocardial infarction within 6 months prior to entry into the study.
• Any significant ECG abnormalities, including second degree AV-block or complete AV-block. Any known significant arrhythmia including atrial flutter, ventricular tachycardia, WPW-syndrome. Any hemodynamically significant valvular heart disease.
• Any significant systemic illnesses or medical condition that could lead to difficulty complying with the protocol.
• Screening or Baseline liver function tests SGOT and/or SGPT > 2.0 times the upper limits of central laboratory normal range.
• Use of systemic and/or inhaled corticosteroids (excluding topical corticosteroids).
• Any additional condition(s), which in the investigator's opinion would prohibit the patient from completing the study, or not be in the best interest of the patient.
• Use of any investigational drugs within 30 days prior to screening.
• Previous exposure to ALT-711.
• Known seropositivity for HIV or hepatitis C, or presence of hepatitis B surface antigen.
• Pregnancy or active breast-feeding. Female patients of childbearing potential (not postmenopausal for at least 5 years or surgically sterilized) must agree not to become pregnant during the duration of the study. Specifically, they must agree to use an appropriate contraceptive regimen. Acceptable regimens include abstinence, systemic hormones, intrauterine devices and barrier methods, such as cervical caps, male or female condoms, or diaphragms with concomitant intravaginal spermicide. A barrier method must have been used without failure for at least 1 year immediately preceding entry into the study.
• Positive drug screen.
• Necessity to use tobacco or nicotine-containing products, or to consume caffeine- containing beverages and/or food, and/or alcohol after midnight prior to clinic visit days, until after any evaluations.