Parallel-Group Comparison of Olmesartan (OLM), Amlodipine (AML) and Hydrochlorothiazid (HCTZ) in Hypertension
Condition: Essential Hypertension
MeSH terms: Hypertension; Essential Hypertension
Intervention: olmesartan medoxomil + amlodipine + hydroclororthiazide + placebo; Olmesartan medoxomil + amlodipine + hydrochlorothiazide + placebo; olmesartan medoxomil + amlodipine + hydroclororthiazide; olmesartan medoxomil + amlodipine + hydroclororthiazide; olmesartan medoxomil + amlodipine + hydroclororthiazide; olmesartan medoxomil + amlodipine; olmesartan medoxomil + amlodipine; olmesartan medoxomil + amlodipine
Intervention description: One olmesartan medoxomil 20 mg + amlodipine 5 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.; One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.; One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day. Two hydrochlorothiazide 12.5 mg tablets taken once per day.; One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.; One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day. Two hydrochlorothiazide 12.5 mg tablets taken once per day.; One olmesartan medoxomil 20 mg + amlodipine 5 mg combination oral tablet taken once per day; One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day.; One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day.
Intervention MeSH terms: Amlodipine; Hydrochlorothiazide; Olmesartan; Olmesartan Medoxomil; Amlodipine Besylate, Olmesartan Medoxomil Drug Combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 2689.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: triple combination; parallel group; dual combination

Summary:

      This study is to determine the change in blood pressure from the administration of
      Olmesartan/Amlodipine/Hydrochlorothiazide triple combinations compared to dual combinations
      with Olmesartan/Amlodipine.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female subjects aged 18 years or older.

          -  Subjects with mean trough seated blood pressure (SeBP) ≥ 160/100 mmHg, (seated
             systolic blood pressure(SeSBP) ≥ 160 mmHg and seated diastolic blood pressure (SeDBP)
             ≥ 100 mmHg) at Screening if not currently on antihypertensive medication (newly
             diagnosed subjects or subjects who are not taking any antihypertensive medication for
             at least 3 weeks); Or Subjects with mean trough SeBP ≥ 160/100 mmHg, SeSBP ≥ 160 mmHg
             and SeDBP ≥ 100 mmHg) after washout of prior antihypertensive medication in subjects
             who discontinued their previous antihypertensive medication.

        The difference in mean SeSBP/SeDBP between the visit prior to randomisation and the
        randomisation visit must be ≤ 20/10 mmHg. Subjects not currently on antihypertensive (HTN)
        medication may meet this requirement at the screening visit (Visit 1) and the randomization
        visit (Visit 3). Subjects washing out of HTN medication must meet this requirement at least
        by Visit 2 (or Visit 2.1, if needed) and Visit 3. All subjects undergoing washout of their
        prior antihypertensive medication will have the opportunity to re-visit the study sites for
        additional visits during washout (Visits 2 and 2.1) to assess eligibility for
        randomisation.

          -  Subjects freely sign the informed consent form (ICF) after the nature of the study and
             the disclosure of his/her data has been explained.

          -  Female subjects of childbearing potential must be using adequate contraception (female
             of childbearing potential is defined as one who has not been postmenopausal for at
             least one year, or has not been surgically sterilised, or has not had a hysterectomy
             at least three months prior to the start of this study [Visit 1]). Adequate
             contraceptives include hormonal intra-uterine devices, hormonal contraceptives (oral,
             depot, patch or injectable), and double barrier methods such as condoms or diaphragms
             with spermicidal gel or foam.

        Exclusion Criteria:

          -  Female subjects of childbearing potential who are pregnant or lactating.

          -  Subjects with serious disorders which may limit the ability to evaluate the efficacy
             or safety of the investigational products, including cerebrovascular, cardiovascular,
             renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, haematologic
             or, neurologic, and psychiatric diseases. The same applies for immunocompromised
             and/or neutropenic subjects.

          -  Subjects having a history of the following within the last six months: myocardial
             infarction (MI), unstable angina pectoris, percutaneous coronary intervention, heart
             failure, hypertensive encephalopathy, cerebrovascular accident (stroke), or transient
             ischaemic attack.

          -  Subjects with clinically significant abnormal laboratory values at Screening,
             including subjects with one or more of the following:

               -  Aspartate aminotransferase (AST) > 3 times upper limit of normal (ULN).

               -  Alanine aminotransferase (ALT) > 3 times ULN.

               -  Gamma-glutamyl transferase (GGT) > 3 times ULN.

               -  Potassium above ULN (unless high value is due to haemolytic blood sample).

          -  Subjects with secondary hypertension of any aetiology such as renal disease,
             phaeochromocytoma, or Cushing's syndrome.

          -  Subjects with contraindication to olmesartan, amlodipine, hydrochlorothiazide, or any
             of the tablet's excipients.

          -  Newly diagnosed subjects with a mean trough SeSBP > 200 mmHg or mean trough SeDBP >
             115 mmHg or any subjects with bradycardia (heart rate < 50 beats/min at rest
             documented by mean radial pulse rate [PR] or electrocardiogram [ECG]) at Screening
             (Visit 1) or immediately before taking Period I study medication (Visit 3).

          -  Subjects already taking four or more antihypertensive medications.

          -  Subjects with a mean trough SeSBP > 145 mmHg or mean trough SeDBP > 95 mmHg while
             taking three antihypertensive medications.

          -  Subjects with a mean trough SeSBP > 160 mmHg or mean trough SeDBP > 100 mmHg while
             taking two antihypertensive medications.

          -  Subjects with a mean trough SeSBP > 180 mmHg or mean trough SeDBP > 110 mmHg while
             taking one antihypertensive medication.

          -  Subjects with electrocardiogram evidence of 2nd or 3rd degree atrio ventricular (AV)
             block, atrial fibrillation, or other cardiac arrhythmia (requiring treatment).

          -  Subjects with severe heart failure (New York Heart Association stage III-IV),
             clinically significant aortic or mitral valve stenosis, uncorrected coarctation of the
             aorta, obstruction of cardiac outflow (obstructive, hypertrophic cardiomyopathy) or
             symptomatic coronary disease.

          -  Subjects with clinical evidence of renal disease including reno-vascular occlusive
             disease, nephrectomy and/or renal transplant, bilateral renal artery stenosis,
             unilateral renal artery stenosis in a solitary kidney, or severe renal impairment as
             evidenced by CrCl of < 30 mL/min calculated using the Cockcroft and Gault formula.

          -  Subjects with clinically relevant hepatic impairment.

          -  Subjects with biliary obstruction.

          -  Subjects with uncontrolled Type 1 or Type 2 diabetes defined as HbA1c > 9.0%.
             Diabetics must have documentation of HbA1c within 6 months of the Screening Visit, or
             must have their HbA1c assessed prior to randomisation. Note: subjects with Type 1 or
             Type 2 diabetes controlled with insulin, diet or oral hypoglycaemic agents on a stable
             dose for at least 30 days may be included.

          -  Subjects with a history of a wasting disease (e.g. cancer), autoimmune diseases,
             connective tissue diseases, major allergies or angioneurotic oedema.

          -  Subjects who require or are taking any concomitant medication which may interfere with
             the objectives of the study.

          -  Subjects on beta blockers or calcium channel blockers (CCBs) for both hypertension and
             either ischemia, post-MI prophylaxis or tachyarrhythmias.

          -  Subjects with known malabsorption syndromes.

          -  Subjects with psychiatric or emotional problems, which would invalidate the giving of
             informed consent or limit the ability of the subject to comply with study
             requirements.

          -  Subjects with a history of alcohol and/or drug abuse.

          -  Subjects who have received any investigational agent within 30 days prior to
             Screening.

          -  Subjects who are unwilling or unable to provide informed consent or to participate
             satisfactorily for the entire study.

          -  Subjects with malignancy during the past 2 years excluding squamous cell or basal cell
             carcinoma of the skin.

          -  Subjects with signs or symptoms which could exacerbate the occurrence of hypotension
             such as volume and salt depletion.

          -  Subjects with any medical condition, which in the judgment of the Investigator would
             jeopardise the evaluation of efficacy or safety and/or constitute a significant safety
             risk to the subject.