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.
Inclusion Criteria:
- Male or female subjects aged 18 years or older.
- Subjects with mean trough SeBP ≥ 160/100 mmHg (SeSBP ≥ 160 mmHg and 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 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 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.
- 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 ECG 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; Recruiting
Buizingen, Belgium; Recruiting
De Pinte, Belgium; Recruiting
Drongen, Belgium; Recruiting
Gent, Belgium; Recruiting
Gilly, Belgium; Recruiting
Merksem, Belgium; Recruiting
Mouscron, Belgium; Recruiting
Tremelo, Belgium; Recruiting
Wichelen, Belgium; Recruiting
Burgas, Bulgaria; Recruiting
Pleven, Bulgaria; Recruiting
Plovdiv, Bulgaria; Recruiting
Sofia, Bulgaria; Recruiting
Stara Zagora, Bulgaria; Recruiting
Veliko Tarnovo, Bulgaria; Recruiting
Benatky nad Jizerou, Czech Republic; Recruiting
Brodce, Czech Republic; Recruiting
Havirov, Czech Republic; Recruiting
Jicin, Czech Republic; Recruiting
Mlada Boleslav, Czech Republic; Recruiting
Moravska Ostrava, Czech Republic; Recruiting
Plzen, Czech Republic; Recruiting
Prachatice, Czech Republic; Recruiting
Praha, Czech Republic; Recruiting
Sokolov, Czech Republic; Recruiting
Copenhagen, Denmark; Recruiting
Frederiksberg, Denmark; Recruiting
Roskilde, Denmark; Recruiting
Berlin, Germany; Recruiting
Cloppenburg, Germany; Recruiting
Delitzsch, Germany; Recruiting
Dresden, Germany; Recruiting
Erfurt, Germany; Recruiting
Essen, Germany; Recruiting
Hamburg, Germany; Recruiting
Heidelberg, Germany; Recruiting
Leipzig, Germany; Recruiting
Northeim, Germany; Recruiting
Simmern, Germany; Recruiting
Wallerfing, Germany; Recruiting
Wiesbaden, Germany; Recruiting
Budapest, Hungary; Recruiting
Debrecen, Hungary; Recruiting
Hodmezovasarhely, Hungary; Recruiting
Jaszbereny, Hungary; Recruiting
Kaposvar, Hungary; Recruiting
Kecskemet, Hungary; Recruiting
Oroshaza, Hungary; Recruiting
Pecs, Hungary; Recruiting
Szekesfehervar, Hungary; Recruiting
Veszprem, Hungary; Recruiting
Zalaegerszeg, Hungary; Recruiting
Bologna, Italy; Recruiting
Brescia, Italy; Recruiting
Chieti, Italy; Recruiting
Ferrara, Italy; Recruiting
Foggia, Italy; Recruiting
Genova, Italy; Recruiting
Palermo, Italy; Recruiting
Parma, Italy; Recruiting
Perugia, Italy; Recruiting
Pisa, Italy; Recruiting
Roma, Italy; Recruiting
Sassari, Italy; Recruiting
Stradella Pavia, Italy; Recruiting
Cesis, Latvia; Recruiting
Daugavpils, Latvia; Recruiting
Jekabpils, Latvia; Recruiting
Ogre, Latvia; Recruiting
Riga, Latvia; Recruiting
Tukums, Latvia; Recruiting
Varaklani, Latvia; Recruiting
Ventspils, Latvia; Recruiting
Deurne, Netherlands; Recruiting
Eindhoven, Netherlands; Recruiting
Lichtenvoorde, Netherlands; Recruiting
Lieshout, Netherlands; Recruiting
Rotterdam, Netherlands; Recruiting
Utrecht, Netherlands; Recruiting
Bialystok, Poland; Recruiting
Debica, Poland; Recruiting
Gdansk, Poland; Recruiting
Gdynia, Poland; Recruiting
Jastrzebia Zdroj, Poland; Recruiting
Krakow, Poland; Recruiting
Lublin, Poland; Recruiting
Mielec, Poland; Recruiting
Opole, Poland; Recruiting
Szczecin, Poland; Recruiting
Warsaw, Poland; Recruiting
Wroclaw, Poland; Recruiting
Arad, Romania; Recruiting
Bucharest, Romania; Recruiting
Craiova, Romania; Recruiting
Iasi, Romania; Recruiting
Pitesti, Romania; Recruiting
Ploiesti, Romania; Recruiting
Sibiu, Romania; Recruiting
Suceava, Romania; Recruiting
Timisoara, Romania; Recruiting
Barnaul, Russian Federation; Recruiting
Moscow, Russian Federation; Recruiting
Novosibirsk, Russian Federation; Recruiting
Saint Petersburg, Russian Federation; Recruiting
Tyumen, Russian Federation; Recruiting
Yaroslavl, Russian Federation; Recruiting
Banska Bysterica, Slovakia; Recruiting
Bratilslava, Slovakia; Recruiting
Nitra, Slovakia; Recruiting
Povazska Bystrica, Slovakia; Recruiting
Rimavska Sobota, Slovakia; Recruiting
Zilina, Slovakia; Recruiting
Badalona, Spain; Recruiting
Barcelona, Spain; Recruiting
Ferrol, Spain; Recruiting
Lleida, Spain; Recruiting
Madrid, Spain; Recruiting
Petrer, Spain; Recruiting
Salamanca, Spain; Recruiting
Santiago de Compostela, Spain; Recruiting
Valencia, Spain; Recruiting
Dnipropetrovsk, Ukraine; Recruiting
Donetsk, Ukraine; Recruiting
Kharkiv, Ukraine; Recruiting
Kyiv, Ukraine; Recruiting
Lutsk, Ukraine; Recruiting
Lviv, Ukraine; Recruiting
Odesa, Ukraine; Recruiting
Simferopol, Ukraine; Recruiting
Vinnytsya, Ukraine; Recruiting
Zaporizhzhya, Ukraine; Recruiting
Zhytomyr, Ukraine; Recruiting
