Safety and Efficacy Study of a Triple Combination Therapy in Subjects With Hypertension
Condition: Hypertension
MeSH terms: Hypertension
Intervention: Olmesartan medoxomil; Amlodipine; Hydrochlorothiazide
Intervention description: 40mg olmesartan medoxomil; Amlodipine 10mg; Hydrochlorothiazide 25mg
Intervention MeSH terms: Amlodipine; Hydrochlorothiazide; Olmesartan; Olmesartan Medoxomil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 2500.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      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.