Hydrochlorothiazide as add-on to Olmesartan/Amlodipine in Hypertension
Condition: Essential Hypertension
MeSH terms: Hypertension; Essential Hypertension
Intervention: Olmesartan medoxomil 40 mg - Amlodipine 10 mg; Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 12.5mg; Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 25mg; OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg; OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg; OLM 40mg-AML 10mg-Hydrochlorothiazide 25mg
Intervention description: Oral tablets containing Olmesartan medoxomil-Amlodipine 40-10 mg, given once daily; Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.; Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 2 Hydrochlorothiazide 12.5mg oral tablets. All tablets are given once a day.; Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.; Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.; Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 2 Hydrochlorothiazide 12.5mg oral tablet. All tablets are given once a day.
Intervention MeSH terms: Amlodipine; Hydrochlorothiazide; Olmesartan; Olmesartan Medoxomil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 2204.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Add on treatment; essential hypertension

Summary:

      Both Olmesartan (OLM)/Amlodipine (AML) combination and Hydrochlorothiazide (HCTZ) have proven
      to be efficacious and safe in lowering blood pressure, but may not always be sufficient. This
      study is to test efficacy and safety of the combination of OLM/AML and HCTZ in hypertensive
      patients whose blood pressure is not adequately controlled with OLM/AML alone. The following
      treatments will be included in the trial: OLM 40mg/AML 10mg; OLM 40mg/AML 10 mg/HCTZ 12.5 mg;
      OLM 40 mg/AML 10 mg/HCTZ 25 mg. The trial has four periods. The treatments that will be used
      are as follows:

      Period 1 - OLM 40mg/AML 10mg; Period 2 - OLM 40mg/AML 10mg or OLM 40mg/AML 10 mg/HCTZ 12.5 mg
      or OLM 40 mg/AML 10 mg/HCTZ 25 mg; Period 3 - OLM 40mg/AML 10 mg/HCTZ 12.5 mg; Period 4 -
      Period 3 responders: OLM 40mg/AML 10 mg/HCTZ 12.5 mg; Period 4 - Period 3 non-responders: OLM
      40mg/AML 10 mg/HCTZ 12.5 mg or OLM 40 mg/AML 10 mg/HCTZ 25 mg
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female aged 18 years or older.

          -  Mean trough seated systolic blood pressure (SeSBP) of ≥ 160/100 mmHg (SeSBP of ≥ 160
             mmHg and seated diastolic blood pressure (SeDBP) ≥ 100 mmHg) at screening if not
             currently on antihypertensive medication (e.g. newly diagnosed subjects)

        OR:

        For subjects on monotherapy: mean trough SeSBP of ≥ 150/95 mmHg (SeSBP of ≥ 150 mmHg and
        SeDBP ≥ 95 mmHg) at screening

        OR:

        For subjects on any combination of antihypertensive medications that includes either
        hydrochlorothiazide or amlodipine or olmesartan for a duration of at least four weeks: mean
        trough SeSBP of ≥ 140/90 mmHg (SeSBP of ≥ 140 mmHg and SeDBP ≥ 90 mmHg) at screening

        OR:

        For subjects on any other combination of antihypertensive medications that includes neither
        hydrochlorothiazide, amlodipine nor olmesartan: mean trough SeSBP ≥ 160 mmHg, mean trough
        SeDBP ≥ 100mmHg, at the end of the taper-off period

          -  Subject freely signs 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]). Females taking oral
             contraceptives should have been on therapy for at least three months. 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. If a female becomes pregnant during the study, she has
             to be withdrawn immediately.

        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, haematological
             or oncological, neurological, 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-glutamyltransferase (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 excipients.

          -  Subjects with a mean SeSBP > 200 mmHg or mean SeDBP > 115 mmHg or 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 2).