Both Olmesartan/Amlodipine combination and Hydrochlorothiazide 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 olmesartan/amlodipine and hydrochlorothiazide in hypertensive patients whose blood pressure is not adequately controlled with olmesartan/amlodipine alone.

• Drug: Olmesartan medoxomil/Amlodipine
  film coated tablet Olmesartan medoxomil/Amlodipine 40/10 mg once daily
• Drug: Hydrochlorothiazide
  tablet, 12.5 mg, once daily

• 1: Active Comparator
  Intervention: Drug: Olmesartan medoxomil/Amlodipine
• 2: Active Comparator
  Interventions:

  • Drug: Olmesartan medoxomil/Amlodipine
  • Drug: Hydrochlorothiazide

Inclusion Criteria:

• Male or female aged 18 years or older.
• Mean trough SeBP of ≥ 160/100 mmHg (SeSBP of ≥ 160 mmHg and SeDBP ≥ 100 mmHg) at Screening if not currently on antihypertensive medication (e.g. newly diagnosed subjects) and a mean 24-hour DBP of at least 85 mmHg with at least 30% of daytime DBP readings over 90 mmHg.

OR:

For subjects on monotherapy: mean trough SeBP of ≥ 150/95 mmHg (SeSBP of ≥ 150 mmHg and SeDBP ≥ 95 mmHg) at Screening and mean 24-hour DBP of at least 80 mmHg and with at least 30% of daytime DBP readings over 85 mmHg.

OR:

For subjects on any combination of antihypertensive medications that includes either HCTZ or AML for a duration of at least four weeks: mean trough SeBP of ≥ 140/90 mmHg (SeSBP of ≥ 140 mmHg and SeDBP ≥ 90 mmHg) at Screening and mean 24-hour DBP of at least 80 mmHg and with at least 30% of daytime DBP readings over 85 mmHg.

OR:

For subjects on any other combination of antihypertensive medications that includes neither HCTZ nor AML: mean trough SeSBP ≥ 160 mmHg, mean trough SeDBP ≥ 100mmHg, at the end of the taper-off period and a mean 24-hour DBP of at least 85 mmHg, assessed by 24-hour ABPM, with at least 30% of daytime DBP readings above 90 mmHg.

• 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 HTN of any aetiology such as renal disease, phaeochromocytoma, or Cushing's syndrome.
• Subjects with contraindication to OM, AML, HCTZ, 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).