Hydrochlorothiazide as add-on to Olmesartan/Amlodipine in Hypertension

NCT ID: NCT00902538

Last Updated: 2019-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 2204 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2010-10-31

Brief Summary

Both Olmesartan (OLM)/Amlodipine (AML) combination and Hydrochlorothiazide (HCTZ) have proven to be efficacious and safe in lowering blood pressure, but may not always be sufficient. This study is to test efficacy and safety of the combination of OLM/AML and HCTZ in hypertensive patients whose blood pressure is not adequately controlled with OLM/AML alone. The following treatments will be included in the trial: OLM 40mg/AML 10mg; OLM 40mg/AML 10 mg/HCTZ 12.5 mg; OLM 40 mg/AML 10 mg/HCTZ 25 mg. The trial has four periods. The treatments that will be used are as follows:

Period 1 - OLM 40mg/AML 10mg; Period 2 - OLM 40mg/AML 10mg or OLM 40mg/AML 10 mg/HCTZ 12.5 mg or OLM 40 mg/AML 10 mg/HCTZ 25 mg; Period 3 - OLM 40mg/AML 10 mg/HCTZ 12.5 mg; Period 4 - Period 3 responders: OLM 40mg/AML 10 mg/HCTZ 12.5 mg; Period 4 - Period 3 non-responders: OLM 40mg/AML 10 mg/HCTZ 12.5 mg or OLM 40 mg/AML 10 mg/HCTZ 25 mg

Conditions

Essential Hypertension

Study Design

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

Study Groups

Olmesartan (OLM) 40mg-Amlodipine (AML) 10mg

The participants in this arm received these 2 drugs for the 8-week, single-blind, run-in Period 1. Participants could then randomized to this same combination for an additional 8 weeks in the double-blind, Period 2.

Group Type: EXPERIMENTAL

Olmesartan medoxomil 40 mg - Amlodipine 10 mg

Intervention Type: DRUG

Oral tablets containing Olmesartan medoxomil-Amlodipine 40-10 mg, given once daily

Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 12.5mg

Participants could start receiving this combination in randomized, double-blind, 8-week Period 2. This combination was continued into single-blind, 8-week Period 3 for all participants entering Period 3.

Group Type: EXPERIMENTAL

Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 12.5mg

Intervention Type: DRUG

Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.

Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 25mg

Participants could start receiving this combination in randomized, double-blind, 8- week Period 2.

Group Type: EXPERIMENTAL

Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 25mg

Intervention Type: DRUG

Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 2 Hydrochlorothiazide 12.5mg oral tablets. All tablets are given once a day.

OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg (Responders)

Participants who meet their blood pressure goals in Period 3 and continued into the 8-week, double-blind Period 4 continued to receive this combination.

Group Type: EXPERIMENTAL

OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg

Intervention Type: DRUG

Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.

OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg (Non-responders)

Participants finishing Period 3, but, who did not meet their blood pressure goals could receive this combination in the double-blind, randomized, Period 4

Group Type: EXPERIMENTAL

OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg

Intervention Type: DRUG

Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.

OLM 40mg-AML 10mg-Hydrochlorothiazide 25mg (Non-responders)

Participants finishing Period 3, but, who did not meet their blood pressure goals could receive this combination in the double-blind, randomized, Period 4

Group Type: EXPERIMENTAL

OLM 40mg-AML 10mg-Hydrochlorothiazide 25mg

Intervention Type: DRUG

Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 2 Hydrochlorothiazide 12.5mg oral tablet. All tablets are given once a day.

Interventions

Olmesartan medoxomil 40 mg - Amlodipine 10 mg

Oral tablets containing Olmesartan medoxomil-Amlodipine 40-10 mg, given once daily

Intervention Type: DRUG

Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 12.5mg

Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.

Intervention Type: DRUG

Olmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 25mg

Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 2 Hydrochlorothiazide 12.5mg oral tablets. All tablets are given once a day.

Intervention Type: DRUG

OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg

Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.

Intervention Type: DRUG

OLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg

Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.

Intervention Type: DRUG

OLM 40mg-AML 10mg-Hydrochlorothiazide 25mg

Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 2 Hydrochlorothiazide 12.5mg oral tablet. All tablets are given once a day.

Intervention Type: DRUG

Other Intervention Names

Olmesartan 40mg-Amlodipine 10mg tablet + 2 Hydrochlorothiazide 12.5mg tablets

Eligibility Criteria

Inclusion Criteria

• Male or female aged 18 years or older.
• Mean trough seated systolic blood pressure (SeSBP) of ≥ 160/100 mmHg (SeSBP of ≥ 160 mmHg and seated diastolic blood pressure (SeDBP) ≥ 100 mmHg) at screening if not currently on antihypertensive medication (e.g. newly diagnosed subjects)

OR:

For subjects on monotherapy: mean trough SeSBP 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 hydrochlorothiazide or amlodipine or olmesartan for a duration of at least four weeks: mean trough SeSBP 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 hydrochlorothiazide, amlodipine nor olmesartan: mean trough SeSBP ≥ 160 mmHg, mean trough SeDBP ≥ 100mmHg, at the end of the taper-off period

• Subject freely signs 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]). Females taking oral contraceptives should have been on therapy for at least three months. 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. If a female becomes pregnant during the study, she has to be withdrawn immediately.

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, haematological or oncological, neurological, 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-glutamyltransferase (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 excipients.
• Subjects with a mean SeSBP > 200 mmHg or mean SeDBP > 115 mmHg or 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 2).

• 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

Graz, , Austria

Salzburg, , Austria

Vienna, , Austria

Antwerp, , Belgium

Lauwe, , Belgium

Leuven, , Belgium

Liège, , Belgium

Massemen, , Belgium

Oostham, , Belgium

Haskovo, , Bulgaria

Pleven, , Bulgaria

Plovdiv, , Bulgaria

Sofia, , Bulgaria

Varna, , Bulgaria

Bílovec, , Czechia

Brno, , Czechia

Havlíčkův Brod, , Czechia

Hodonín, , Czechia

Kladno, , Czechia

Kolín, , Czechia

Ostrava, , Czechia

Ostrava-Vitkovice, , Czechia

Prague, , Czechia

Copenhagen, , Denmark

Frederiksberg, , Denmark

Næstved, , Denmark

Roskilde, , Denmark

Albi, , France

Angers, , France

Brest, , France

Cambrai, , France

Créteil, , France

Dijon, , France

Dinard, , France

Lyon, , France

Nancy, , France

Pessac, , France

Roubaix, , France

Strasbourg, , France

Tiercé, , France

Vandœuvre-lès-Nancy, , France

Villefranche-de-Rouergue, , France

Berlin, , Germany

Dresden, , Germany

Einbeck, , Germany

Hamburg, , Germany

Magdeburg, , Germany

München, , Germany

Straßkirchen, , Germany

Villingen-Schwenningen, , Germany

Wermsdorf, , Germany

Almere Stad, , Netherlands

Beek en Donk, , Netherlands

Doetinchem, , Netherlands

Groningen, , Netherlands

Losser, , Netherlands

Maastricht, , Netherlands

Bytom, , Poland

Gdansk, , Poland

Katowice, , Poland

Krakow, , Poland

Piotrkow Trybunalski, , Poland

Puławy, , Poland

Siemianowice Śląskie, , Poland

Tarnów, , Poland

Torun, , Poland

Warsaw, , Poland

Wroclaw, , Poland

Brasov, , Romania

Bucharest, , Romania

Cluj-Napoca, , Romania

Iași, , Romania

Oradea, , Romania

Piteşti, , Romania

Târgovişte, , Romania

Târgu Mureş, , Romania

Timișoara, , Romania

Moscow, , Russia

Novosibirsk, , Russia

Orenburg, , Russia

Ryazan, , Russia

Saint Petersburg, , Russia

Saratov, , Russia

Smolensk, , Russia

Tomsk, , Russia

Yaroslavl, , Russia

Yekaterinburg, , Russia

Banska Bysterica, , Slovakia

Brastislava, , Slovakia

Dolný Kubín, , Slovakia

Košice, , Slovakia

Prešov, , Slovakia

Šahy, , Slovakia

La Gineta, Albacete, Spain

La Roda, Albacete, Spain

Port de Sagunt, Valencia, Spain

Alicante, , Spain

Barcelona, , Spain

Elche, , Spain

Granada, , Spain

Madrid, , Spain

Palma de Mallorca, , Spain

Seville, , Spain

Valencia, , Spain

Vizcaya, , Spain

Dnipropetrovsk, , Ukraine

Donetsk, , Ukraine

Ivano-Frankivsk, , Ukraine

Kharkiv, , Ukraine

Kiev, , Ukraine

Lviv, , Ukraine

Mykolayiv, , Ukraine

Odesa, , Ukraine

Simferopol, , Ukraine

Uzhhorod, , Ukraine

Vinnytsia, , Ukraine

Yalta, , Ukraine

Countries

Austria; Belgium; Bulgaria; Czechia; Denmark; France; Germany; Netherlands; Poland; Romania; Russia; Slovakia; Spain; Ukraine

Other Identifiers

CS8635-A-E303

Identifier Type: -

Identifier Source: org_study_id