Safety and Efficacy Study of a Triple Combination Therapy in Subjects With Hypertension

To determine the effectiveness of four different strength combinations of three approved anti-hypertension therapies (olmesartan medoxomil, amlodipine, and hydrochlorothiazide) for lowering blood pressure.


Eligibility Criteria:
Inclusion Criteria:

* Demonstrable hypertension defined as mean sitting trough cuff blood pressure ≥ 140/100 mmHg (SeSBP ≥ 140 mmHg and SeDBP ≥ 100mmHg) or mean sitting trough cuff BP ≥ 160/90 mmHg (SeSBP ≥ 160 mmHg and SeDBP ≥ 90mmHg).
* Male or female newly diagnosed hypertensive subjects or currently on hypertension medication.

  * Negative urine pregnancy test at screening
  * Not lactating
  * Do not plan to become pregnant during the study
  * Will practice birth control throughout the study by the following: oral or patch contraceptive, injectable or implantable contraceptive medication, intrauterine device, diaphragm or female condom plus spermicide

    * Non childbearing potential must be classified by one of the following criteria
    * Had a hysterectomy or tubal ligation at least 6 months prior to consent
    * Has been postmenopausal for a least 1 year

Exclusion Criteria:

* Mean sitting trough cuff DBP \<90 mmHg or mean sitting trough cuff SBP \<140 mmHg (off antihypertensive medication).
* Subjects with uncontrolled hypertension taking multiple antihypertensive therapies (at the discretion of the investigator).
* Signs or symptoms which could exacerbate the occurrence of hypotension such as volume and salt depletion.
* History of hypertensive encephalopathy, stroke or transient ischemic attack (TIA).
* Participation in another clinical trial involving an investigational drug within one month prior to screening.
* History of myocardial infarction, percutaneous transluminal coronary revascularization, coronary artery bypass graft, and/or unstable angina within the past 6 months.
* Any history of New York Heart Association Class III or IV congestive heart failure (CHF). A history of New York Heart Association Class I or II CHF may be exclusionary at the discretion of the investigator.
* History of secondary hypertension including renal disease, pheochromocytoma, or Cushing's syndrome.
* Uncorrected coarctation of the aorta, bilateral renal artery stenosis, or unilateral renal artery stenosis in a solitary kidney.
* Evidence of symptomatic resting bradycardia.
* Evidence of hemodynamically significant cardiac valvular disease.
* Presence of heart block greater than first degree atrioventricular block, chronic atrial fibrillation or flutter.
* Uncontrolled Type I or Type II diabetes defined as HbA1c \>9.0%. Diabetics must have documentation of HbA1c within 6 months of the Screening Visit. Undocumented subjects must have their HbA1c assessed prior to randomization. Note: Subjects with Type I or Type II diabetes controlled with insulin, diet or oral hypoglycemic agents on a stable dose for at least 30 days may be included.
* Evidence of liver disease as indicated by ALT and AST and/or total bilirubin \>3 times the upper limit of normal.
* Severe renal insufficiency defined as a creatinine clearance (based on the Cockcroft-Gault formula) of \<30 mL/min.
* Clinically significant laboratory elevations at Visit 1 that compromise subject safety, based on the investigator's judgment. Consideration should take into account the potential laboratory effects of the component blinded therapies.
* Positive for any one of the following tests: hepatitis B surface antigen, hepatitis C antibody (confirmed by radio immunobinding assay, RIBA) or HIV antibody (confirmed by western blot assay).
* Subjects with malignancy during the past 2 years excluding squamous cell or basal cell carcinoma of the skin.
* Known allergy to any of the medications used in the study.
* Subjects who require or are taking any concomitant medication, which may interfere with the objectives of the study (Refer to Section 5.2 for a listing of excluded medications).
* Pregnant or lactating females.
* Current history of drug or alcohol abuse.
* A subject with any medical condition, which in the judgment of the Investigator would jeopardize the evaluation of efficacy or safety and/or constitute a significant safety risk to the subject.