Clinical trial NCT00923091: Parallel-Group Comparison of Olmesartan (OLM), Amlodipine (AML) and Hydrochlorothiazid (HCTZ) in Hypertension
Official title: Randomised, Double-Blind, Parallel-Group Study Evaluating Efficacy and Safety of Co-Administration of Triple Combinations of Olmesartan Medoxomil, Amlodipine Besylate, and Hydrochlorothiazide Compared With Corresponding Olmesartan - Amlodipine Combination in Subjects With Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Essential Hypertension
Keywords: triple combination
parallel group
dual combination
Lead sponsor: Daiichi Sankyo
Sponsor class: INDUSTRY
First posted: 2009-06-18
Enrollment: 2689
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in Seated Diastolic Blood Pressure (SeDBP).
timeFrame: Baseline to week 10
Secondary outcomes:
measure: Change in Seated Systolic Blood Pressure (SeDBP).
timeFrame: Baseline to week 10
measure: Number of Subjects Reaching Blood Pressure Goal at Week 10
timeFrame: baseline to week 10
measure: Change in Seated Diastolic Blood Pressure From Week 18 to Week 22
timeFrame: Week 18 to week 22
measure: Change in Seated Systolic Blood Pressure From Week 18 to Week 22
timeFrame: Week 18 to week 22
measure: Number of Subjects Reaching Blood Pressure Goal From Week 18 to Week 22
timeFrame: Week 18 to week 22
measure: Change in Seated Diastolic Blood Pressure From Week 22 to Week 26
timeFrame: Week 22 to week 26
measure: Change in Seated Systolic Blood Pressure From Week 22 to Week 26
timeFrame: Week 22 to week 26
measure: Number of Subjects Reaching Blood Pressure Goal at Week 26
timeFrame: Week 22 to week 26
measure: Change in Seated Systolic Blood Pressure (SeDBP) During Open-Label Period VI (Titration Effect From OM/AML/HCTZ 40/5/25 to 40/10/25.
timeFrame: Week 26 to week 54
Other outcomes:
Locations:
city: Antwerp
country: Belgium
city: Buizingen
country: Belgium
city: De Pinte
country: Belgium
city: Drongen
country: Belgium
city: Gent
country: Belgium
city: Gilly
country: Belgium
city: Merksem
country: Belgium
city: Mouscron
country: Belgium
city: Tremelo
country: Belgium
city: Wichelen
country: Belgium
city: Burgas
country: Bulgaria
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Sofia
country: Bulgaria
city: Stara Zagora
country: Bulgaria
city: Veliko Tarnovo
country: Bulgaria
city: Benatky nad Jizerou
country: Czechia
city: Brodce
country: Czechia
city: Havirov
country: Czechia
city: Jicin
country: Czechia
city: Mlada Boleslav
country: Czechia
city: Moravska Ostrava
country: Czechia
city: Plzen
country: Czechia
city: Prachatice
country: Czechia
city: Praha
country: Czechia
city: Sokolov
country: Czechia
city: Copenhagen
country: Denmark
city: Frederiksberg
country: Denmark
city: Roskilde
country: Denmark
city: Berlin
country: Germany
city: Cloppenburg
country: Germany
city: Delitzsch
country: Germany
city: Dresden
country: Germany
city: Erfurt
country: Germany
city: Essen
country: Germany
city: Hamburg
country: Germany
city: Heidelberg
country: Germany
city: Leipzig
country: Germany
city: Northeim
country: Germany
city: Simmern
country: Germany
city: Wallerfing
country: Germany
city: Wiesbaden
country: Germany
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Hodmezovasarhely
country: Hungary
city: Jaszbereny
country: Hungary
city: Kaposvar
country: Hungary
city: Kecskemet
country: Hungary
city: Oroshaza
country: Hungary
city: Pecs
country: Hungary
city: Szekesfehervar
country: Hungary
city: Veszprem
country: Hungary
city: Zalaegerszeg
country: Hungary
city: Bologna
country: Italy
city: Brescia
country: Italy
city: Chieti
country: Italy
city: Ferrara
country: Italy
city: Foggia
country: Italy
city: Genova
country: Italy
city: Palermo
country: Italy
city: Parma
country: Italy
city: Perugia
country: Italy
city: Pisa
country: Italy
city: Roma
country: Italy
city: Sassari
country: Italy
city: Stradella Pavia
country: Italy
city: Cesis
country: Latvia
city: Daugavpils
country: Latvia
city: Jekabpils
country: Latvia
city: Ogre
country: Latvia
city: Riga
country: Latvia
city: Tukums
country: Latvia
city: Varaklani
country: Latvia
city: Ventspils
country: Latvia
city: Deurne
country: Netherlands
city: Eindhoven
country: Netherlands
city: Lichtenvoorde
country: Netherlands
city: Lieshout
country: Netherlands
city: Rotterdam
country: Netherlands
city: Utrecht
country: Netherlands
city: Bialystok
country: Poland
city: Debica
country: Poland
city: Gdansk
country: Poland
city: Gdynia
country: Poland
city: Jastrzebia Zdroj
country: Poland
city: Krakow
country: Poland
city: Lublin
country: Poland
city: Mielec
country: Poland
city: Opole
country: Poland
city: Szczecin
country: Poland
city: Warsaw
country: Poland
city: Wroclaw
country: Poland
city: Arad
country: Romania
city: Bucharest
country: Romania
city: Craiova
country: Romania
city: Iasi
country: Romania
city: Pitesti
country: Romania
city: Ploiesti
country: Romania
city: Sibiu
country: Romania
city: Suceava
country: Romania
city: Timisoara
country: Romania
city: Barnaul
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: Saint Petersburg
country: Russian Federation
city: Tyumen
country: Russian Federation
city: Yaroslavl
country: Russian Federation
city: Banska Bysterica
country: Slovakia
city: Bratilslava
country: Slovakia
city: Nitra
country: Slovakia
city: Povazska Bystrica
country: Slovakia
city: Rimavska Sobota
country: Slovakia
city: Zilina
country: Slovakia
city: Badalona
country: Spain
city: Barcelona
country: Spain
city: Ferrol
country: Spain
city: Lleida
country: Spain
city: Madrid
country: Spain
city: Petrer
country: Spain
city: Salamanca
country: Spain
city: Santiago de Compostela
country: Spain
city: Valencia
country: Spain
city: Dnipropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Kharkiv
country: Ukraine
city: Kyiv
country: Ukraine
city: Lutsk
country: Ukraine
city: Lviv
country: Ukraine
city: Odesa
country: Ukraine
city: Simferopol
country: Ukraine
city: Vinnytsya
country: Ukraine
city: Zaporizhzhya
country: Ukraine
city: Zhytomyr
country: Ukraine
Study officials:
References:
citation: Marques da Silva P, Haag U, Guest JF, Brazier JE, Soro M. Health-related quality of life impact of a triple combination of olmesartan medoxomil, amlodipine besylate and hydrochlorotiazide in subjects with hypertension. Health Qual Life Outcomes. 2015 Feb 21;13:24. doi: 10.1186/s12955-015-0216-6.
citation: Volpe M, de la Sierra A, Ammentorp B, Laeis P. Open-label study assessing the long-term efficacy and safety of triple olmesartan/amlodipine/hydrochlorothiazide combination therapy for hypertension. Adv Ther. 2014 May;31(5):561-74. doi: 10.1007/s12325-014-0117-9. Epub 2014 Apr 24.
citation: Volpe M, Christian Rump L, Ammentorp B, Laeis P. Efficacy and safety of triple antihypertensive therapy with the olmesartan/amlodipine/hydrochlorothiazide combination. Clin Drug Investig. 2012 Oct 1;32(10):649-64. doi: 10.1007/BF03261919.