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

Daiichi Sankyo

Status and phase: Completed; Phase 3

Conditions: Hypertension

Treatments: Drug: Olmesartan medoxomil; Drug: Hydrochlorothiazide; Drug: Amlodipine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00649389

CS8635-A-U301

Details and patient eligibility

About

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

Enrollment: 2,500 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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2,500 participants in 4 patient groups

OM40/AML10

Experimental group

Description:

olmesartan medoxomil 40mg and amlodipine 10mg

Treatment:

Drug: Amlodipine

Drug: Olmesartan medoxomil

OM40/HCTZ25

Active Comparator group

Description:

olmesartan medoxomil 40mg and hydrochlorothiazide 25mg

Treatment:

Drug: Hydrochlorothiazide

Drug: Olmesartan medoxomil

AML10/HCTZ25

Active Comparator group

Description:

amlodipine 10mg and hydrochlorothiazide 25mg

Treatment:

Drug: Hydrochlorothiazide

Drug: Amlodipine

OM40/AML10/HCTZ25

Active Comparator group

Description:

olmesartan medoxomil 40mg, amlodipine 10mg, and hydrochlorothiazide 25mg

Treatment:

Drug: Hydrochlorothiazide

Drug: Amlodipine

Drug: Olmesartan medoxomil