Parallel-Group Comparison of Olmesartan (OLM), Amlodipine (AML) and Hydrochlorothiazid (HCTZ) in Hypertension

NCT ID: NCT00923091

Last Updated: 2019-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 2689 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2011-03-31

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.

Conditions

Essential Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

olmesartan/amlodipine/hydrochlorothiazide 20mg/5mg/12.5mg

olmesartan medoxomil 20mg / amlodipine besylate 5 mg / hydrochlorothiazide 12.5mg

Group Type: EXPERIMENTAL

olmesartan medoxomil + amlodipine + hydroclororthiazide + placebo

Intervention Type: DRUG

One olmesartan medoxomil 20 mg + amlodipine 5 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.

olmesartan/amlodipine/hydrochlorothiazide 40mg/5mg/12.5mg

Group Type: EXPERIMENTAL

Olmesartan medoxomil + amlodipine + hydrochlorothiazide + placebo

Intervention Type: DRUG

One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.

olmesartan/amlodipine/hydrochlorothiazide 40mg/5mg/25mg

Group Type: EXPERIMENTAL

olmesartan medoxomil + amlodipine + hydroclororthiazide

Intervention Type: DRUG

One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day. Two hydrochlorothiazide 12.5 mg tablets taken once per day.

olmesartan/amlodipine/hydrochlorothiazide 40mg/10mg/12.5mg

Group Type: EXPERIMENTAL

olmesartan medoxomil + amlodipine + hydroclororthiazide

Intervention Type: DRUG

One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.

olmesartan/amlodipine/hydrochlorothiazide 40mg/10mg/25mg

Group Type: EXPERIMENTAL

olmesartan medoxomil + amlodipine + hydroclororthiazide

Intervention Type: DRUG

One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day. Two hydrochlorothiazide 12.5 mg tablets taken once per day.

olmesartan/amlodipine 20mg/5mg

olmesartan medoxomil 20mg / amlodipine besylate 5mg

Group Type: EXPERIMENTAL

olmesartan medoxomil + amlodipine

Intervention Type: DRUG

One olmesartan medoxomil 20 mg + amlodipine 5 mg combination oral tablet taken once per day

olmesartan/amlodipine 40mg/5mg

Group Type: EXPERIMENTAL

olmesartan medoxomil + amlodipine

Intervention Type: DRUG

One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day.

olmesartan/amlodipine 40mg/10mg

Group Type: EXPERIMENTAL

olmesartan medoxomil + amlodipine

Intervention Type: DRUG

One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day.

Interventions

olmesartan medoxomil + amlodipine + hydroclororthiazide + placebo

One olmesartan medoxomil 20 mg + amlodipine 5 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.

Intervention Type: DRUG

Olmesartan medoxomil + amlodipine + hydrochlorothiazide + placebo

One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.

Intervention Type: DRUG

olmesartan medoxomil + amlodipine + hydroclororthiazide

One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day. Two hydrochlorothiazide 12.5 mg tablets taken once per day.

Intervention Type: DRUG

olmesartan medoxomil + amlodipine + hydroclororthiazide

One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day. One hydrochlorothiazide 12.5 mg tablet + one hydrochlorothiazide 12.5 mg placebo tablet taken once per day.

Intervention Type: DRUG

olmesartan medoxomil + amlodipine + hydroclororthiazide

One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day. Two hydrochlorothiazide 12.5 mg tablets taken once per day.

Intervention Type: DRUG

olmesartan medoxomil + amlodipine

One olmesartan medoxomil 20 mg + amlodipine 5 mg combination oral tablet taken once per day

Intervention Type: DRUG

olmesartan medoxomil + amlodipine

One olmesartan medoxomil 40 mg + amlodipine 5 mg combination oral tablet taken once per day.

Intervention Type: DRUG

olmesartan medoxomil + amlodipine

One olmesartan medoxomil 40 mg + amlodipine 10 mg combination oral tablet taken once per day.

Intervention Type: DRUG

Other Intervention Names

Azor; Azor; Azor; Norvasc; Azor; Azor; Azor; Azor

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Antwerp, , Belgium

Buizingen, , Belgium

De Pinte, , Belgium

Drongen, , Belgium

Ghent, , 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

Benátky nad Jizerou, , Czechia

Brodce, , Czechia

Havířov, , Czechia

Jičín, , Czechia

Mladá Boleslav, , Czechia

Moravská Ostrava, , Czechia

Pilsen, , Czechia

Prachatice, , Czechia

Prague, , Czechia

Sokolov, , Czechia

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

Hódmezővásárhely, , Hungary

Jászberény, , Hungary

Kaposvár, , Hungary

Kecskemét, , Hungary

Orosháza, , Hungary

Pécs, , Hungary

Székesfehérvár, , Hungary

Veszprém, , 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

Cēsis, , Latvia

Daugavpils, , Latvia

Jēkabpils, , Latvia

Ogre, , Latvia

Riga, , Latvia

Tukums, , Latvia

Varakļāni, , Latvia

Ventspils, , Latvia

Deurne, , Netherlands

Eindhoven, , Netherlands

Lichtenvoorde, , Netherlands

Lieshout, , Netherlands

Rotterdam, , Netherlands

Utrecht, , Netherlands

Bialystok, , Poland

Dębica, , 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

Iași, , Romania

Piteşti, , Romania

Ploieşti, , Romania

Sibiu, , Romania

Suceava, , Romania

Timișoara, , Romania

Barnaul, , Russia

Moscow, , Russia

Novosibirsk, , Russia

Saint Petersburg, , Russia

Tyumen, , Russia

Yaroslavl, , Russia

Banska Bysterica, , Slovakia

Bratilslava, , Slovakia

Nitra, , Slovakia

Považská Bystrica, , Slovakia

Rimavská Sobota, , Slovakia

Žilina, , Slovakia

Badalona, , Spain

Barcelona, , Spain

Ferrol, , Spain

Lleida, , Spain

Madrid, , Spain

Petrel, , 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

Vinnytsia, , Ukraine

Zaporizhzhya, , Ukraine

Zhytomyr, , Ukraine

Countries

Belgium; Bulgaria; Czechia; Denmark; Germany; Hungary; Italy; Latvia; Netherlands; Poland; Romania; Russia; Slovakia; Spain; Ukraine

References

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.

Reference Type: DERIVED

PMID: 25879524 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 24760656 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 22909147 (View on PubMed)

Other Identifiers

CS8635-A-E302

Identifier Type: -

Identifier Source: org_study_id