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.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Antwerp, Belgium
Buizingen, Belgium
De Pinte, Belgium
Drongen, Belgium
Gent, Belgium
Gilly, Belgium
Merksem, Belgium
Mouscron, Belgium
Tremelo, Belgium
Wichelen, Belgium
Burgas, Bulgaria
Pleven, Bulgaria
Plovdiv, Bulgaria
Sofia, Bulgaria
Stara Zagora, Bulgaria
Veliko Tarnovo, Bulgaria
Benatky nad Jizerou, Czech Republic
Brodce, Czech Republic
Havirov, Czech Republic
Jicin, Czech Republic
Mlada Boleslav, Czech Republic
Moravska Ostrava, Czech Republic
Plzen, Czech Republic
Prachatice, Czech Republic
Praha, Czech Republic
Sokolov, Czech Republic
Copenhagen, Denmark
Frederiksberg, Denmark
Roskilde, Denmark
Berlin, Germany
Cloppenburg, Germany
Delitzsch, Germany
Dresden, Germany
Erfurt, Germany
Essen, Germany
Hamburg, Germany
Heidelberg, Germany
Leipzig, Germany
Northeim, Germany
Simmern, Germany
Wallerfing, Germany
Wiesbaden, Germany
Budapest, Hungary
Debrecen, Hungary
Hodmezovasarhely, Hungary
Jaszbereny, Hungary
Kaposvar, Hungary
Kecskemet, Hungary
Oroshaza, Hungary
Pecs, Hungary
Szekesfehervar, Hungary
Veszprem, Hungary
Zalaegerszeg, Hungary
Bologna, Italy
Brescia, Italy
Chieti, Italy
Ferrara, Italy
Foggia, Italy
Genova, Italy
Palermo, Italy
Parma, Italy
Perugia, Italy
Pisa, Italy
Roma, Italy
Sassari, Italy
Stradella Pavia, Italy
Cesis, Latvia
Daugavpils, Latvia
Jekabpils, Latvia
Ogre, Latvia
Riga, Latvia
Tukums, Latvia
Varaklani, Latvia
Ventspils, Latvia
Deurne, Netherlands
Eindhoven, Netherlands
Lichtenvoorde, Netherlands
Lieshout, Netherlands
Rotterdam, Netherlands
Utrecht, Netherlands
Bialystok, Poland
Debica, Poland
Gdansk, Poland
Gdynia, Poland
Jastrzebia Zdroj, Poland
Krakow, Poland
Lublin, Poland
Mielec, Poland
Opole, Poland
Szczecin, Poland
Warsaw, Poland
Wroclaw, Poland
Arad, Romania
Bucharest, Romania
Craiova, Romania
Iasi, Romania
Pitesti, Romania
Ploiesti, Romania
Sibiu, Romania
Suceava, Romania
Timisoara, Romania
Barnaul, Russian Federation
Moscow, Russian Federation
Novosibirsk, Russian Federation
Saint Petersburg, Russian Federation
Tyumen, Russian Federation
Yaroslavl, Russian Federation
Banska Bysterica, Slovakia
Bratilslava, Slovakia
Nitra, Slovakia
Povazska Bystrica, Slovakia
Rimavska Sobota, Slovakia
Zilina, Slovakia
Badalona, Spain
Barcelona, Spain
Ferrol, Spain
Lleida, Spain
Madrid, Spain
Petrer, Spain
Salamanca, Spain
Santiago de Compostela, Spain
Valencia, Spain
Dnipropetrovsk, Ukraine
Donetsk, Ukraine
Kharkiv, Ukraine
Kyiv, Ukraine
Lutsk, Ukraine
Lviv, Ukraine
Odesa, Ukraine
Simferopol, Ukraine
Vinnytsya, Ukraine
Zaporizhzhya, Ukraine
Zhytomyr, Ukraine