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

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

Official Title
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A Randomized, Double-Blind, Parallel Group Study Evaluating the Efficacy and Safety of Co-Administration of a Triple Combination Therapy of Olmesartan Medoxomil, Amlodipine Besylate and Hydrochlorothiazide in Subjects With Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Olmesartan medoxomil
* Drug: Amlodipine
* Drug: Hydrochlorothiazide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OM40/AML10<br>olmesartan medoxomil 40mg and amlodipine 10mg | Drug: Olmesartan medoxomil<br>* 40mg olmesartan medoxomil<br>* Other names: Benicar;Drug: Amlodipine<br>* Amlodipine 10mg<br>* Other names: Norvasc;|
| Active Comparator: OM40/HCTZ25<br>olmesartan medoxomil 40mg and hydrochlorothiazide 25mg | Drug: Olmesartan medoxomil<br>* 40mg olmesartan medoxomil<br>* Other names: Benicar;Drug: Hydrochlorothiazide<br>* Hydrochlorothiazide 25mg<br>|
| Active Comparator: AML10/HCTZ25<br>amlodipine 10mg and hydrochlorothiazide 25mg | Drug: Amlodipine<br>* Amlodipine 10mg<br>* Other names: Norvasc;Drug: Hydrochlorothiazide<br>* Hydrochlorothiazide 25mg<br>|
| Active Comparator: OM40/AML10/HCTZ25<br>olmesartan medoxomil 40mg, amlodipine 10mg, and hydrochlorothiazide 25mg | Drug: Olmesartan medoxomil<br>* 40mg olmesartan medoxomil<br>* Other names: Benicar;Drug: Amlodipine<br>* Amlodipine 10mg<br>* Other names: Norvasc;Drug: Hydrochlorothiazide<br>* Hydrochlorothiazide 25mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 12 in Seated Diastolic Blood Pressure (SeDBP). |  | baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Who Reached Blood Pressure Goal (<140/90 mmHg; <130/80 mmHg for Subjects With Diabetes, Chronic Renal Disease, or Chronic Cardiovascular Disease)by 12 Weeks |  | Baseline to 12 weeks | 
| Change in Mean 24-hour Ambulatory Blood Pressure From Baseline to Week 12 or Early Termination |  | Baseline to 12 weeks or early termination | 
| Change in Seated Systolic Blood Pressure From Baseline to Week 12 |  | Baseline to week 12 |