A RANDOMISED, DOUBLE-BLIND, ADD-ON STUDY OF HYDROCHLOROTHIAZIDE IN SUBJECTS WITH MODERATE TO SEVERE HYPERTENSION NOT ACHIEVING TARGET BLOOD PRESSURE ON OLMESARTAN MEDOXOMIL/AMLODIPINE FIXED DOSE COMBINATION 40/10 MG ALONE

INTERVENTION: Trade Name: Sevikar 40 mg /10 mg Product Name: OM/AML 40/10 mg Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: olmesartan medoxomil CAS Number: 144689‐63‐4 Other descriptive name: OM Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 40‐ INN or Proposed INN: amlodipine besylate CAS Number: 88150‐42‐9 Other descriptive name: AML Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ Trade Name: HCT 12.5‐1 A Pharma Pharmaceutical Form: Tablet INN or Proposed INN: hydrochlorothiazide CAS Number: 58‐93‐5 Other descriptive name: HCTZ Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 12.5‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Essential hypertension ; MedDRA version: 9.1 Level: LLT Classification code 10020772 Term: Hypertension PRIMARY OUTCOME: Main Objective: The primary objective (Period II, Week 8 to Week 16) is to demonstrate the additional antihypertensive efficacy for SeDBP gained by adding HCTZ 12.5 or 25 mg to the treatment regimen in subjects with moderate to severe HTN not adequately controlled on OM/AML 40/10 mg alone, at Week 16 (after 8 weeks of double‐blind treatment) using conventional BP measurement. Primary end point(s): The mean change in trough SeDBP from the randomisation visit (end of the OM/AML run‐in period [Week 8]) to the end of the double‐blind Period II (Week 16). Secondary Objective: Period II: 1. Evaluate antihypertensive efficacy for SeDBP of triple combination OM/AML/HCTZ 40/10/12.5 & 40/10/25 mg vs OM/AML 40/10 mg at Wk(week)12. 2. Evaluate antihypertensive efficacy for SeSBP of OM/AML/HCTZ 40/10/12.5 & 40/10/25mg vs OM/AML 40/10mg at Wk12&16. 3. Evaluate antihypertensive efficacy from baseline to Wk16 (see protocol p36). 4. Evaluate % no. subjects achieving BP goal (SeBP, see protocol p36) and % no. subjects achieving SeBP thresholds (see protocol p.36) at Wk12&16. 5. Evaluate safety & tolerability of triple combination therapy at Wk8‐16. Period III&IV: 1. Evaluate antihypertensive efficacy of up titration of dose to 40/10/25mg in subjects not reaching BP goal on dose 40/10/12.5mg based on changes from Wk24‐32 (see protocol p36). 2. Evaluate % no. subjects achieving BP goal & BP thresholds (defined point 4 above) at Wk32. 3. Evaluate safety & tolerability of triple combination therapy during Wk16‐32. INCLUSION CRITERIA: 1. Male or female aged 18 years or older. 2. 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). OR: For subjects on monotherapy: mean trough SeBP 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 HCTZ, OM 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. OR: For subjects on any other combination of antihypertensive medications that includes neither HCTZ, OM nor AML: mean trough SeSBP = 160 mmHg and mean trough SeDBP = 100mmHg, at the end of the taper‐off period. 3. Subject freely signs ICF after the nature of the study and the disclosure of his/her data has been explained. 4. Female subjects of childbearing potential must b