Hydrochlorothiazide as Add-on to Olmesartan/Amlodipine in Hypertension

Condition(s) targeted: Essential Hypertension

Intervention: Olmesartan medoxomil/Amlodipine (Drug); Hydrochlorothiazide (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: Daiichi Sankyo Inc.

Overall contact:
Esther Janssen, Phone: +33(0)146902451, Email: Esther.Janssen@mdsinc.com

Both Olmesartan/Amlodipine combination and Hydrochlorothiazide 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 olmesartan/amlodipine and hydrochlorothiazide in hypertensive patients whose blood pressure is not adequately controlled with olmesartan/amlodipine alone.

Official title: Add-on Study of Hydrochlorothiazide in Patients With Moderate to Severe Hypertension Not Achieving Target Blood Pressure on Olmesartan/Amlodipine Alone

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: change (week 16 - week 8) in seated diastolic blood pressure (SeDBP) by adding hydrochlorothiazide (HCTZ) 12.5 or 25 mg to 40mg olmesartan medoximil (OM) / 10 mg amlodipine (AML)

Secondary outcome:

change (Week 12 - Week 8) in seated diastolic blood pressure (SeDBP) of the triple combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg at Week 12

change (Week 12 - Week 8) in seated systolic blood pressure (SeSBP) of the triple combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg.

change from Week 8 (baseline) to Week 16, in daytime, diastolic blood pressure (DBP) assessed by 24-hour ambulatory blood pressure measurement (ABPM). change = week 16 - week 8)

number of subjects achieving blood pressure (BP) goal at Week 12. week 12 - week 8

change in daytime DBP following up titration to OM/AML/HCTZ 40/10/25 mg from OM/AML/HCTZ 40/10/12.5 mg in subjects not reaching BP goal as assessed by 24-hour ABPM. (change = Week 32 - Week 16)

number of subjects achieving BP goal and BP thresholds at Week 32. (Week 32 - Week 16)

change (Week 16 - Week 8) in seated systolic blood pressure (SeSBP) of the triple combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg.

change from Week 8 (baseline) to Week 16, in daytime, systolic blood pressure (SBP), assessed by 24-hour ambulatory blood pressure measurement (ABPM). change = week 16 - week 8)

change from Week 8 (baseline) to Week 16, in night time, diastolic blood pressure (DBP) assessed by 24-hour ambulatory blood pressure measurement (ABPM). change = week 16 - week 8)

change from Week 8 (baseline) to Week 16, night time, systolic blood pressure (SBP), assessed by 24-hour ambulatory blood pressure measurement (ABPM). change = week 16 - week 8)

change from Week 8 (baseline) to Week 16, in 24-hour diastolic blood pressure (DBP) assessed by 24-hour ambulatory blood pressure measurement (ABPM). change = week 16 - week 8)

change from Week 8 (baseline) to Week 16, in 24-hour systolic blood pressure (SBP), assessed by 24-hour ambulatory blood pressure measurement (ABPM). change = week 16 - week 8)

number of subjects achieving blood pressure (BP) goal at Week 16. week 16 - week 8

number of subjects SeBP threshold at Week 12. week 12 - week 8

number of subjects achieving SeBP threshold at Week 16. week 16 - week 8.

number of subjects achieving BP thresholds at Week 32. (Week 32 - Week 16)

change in daytime SBP following up titration to OM/AML/HCTZ 40/10/25 mg from OM/AML/HCTZ 40/10/12.5 mg in subjects not reaching BP goal as assessed by 24-hour ABPM. (change = Week 32 - Week 16)

change in night-time DBP following up titration to OM/AML/HCTZ 40/10/25 mg from OM/AML/HCTZ 40/10/12.5 mg in subjects not reaching BP goal as assessed by 24-hour ABPM. (change = Week 32 - Week 16)

change in night-time SBP following up titration to OM/AML/HCTZ 40/10/25 mg from OM/AML/HCTZ 40/10/12.5 mg in subjects not reaching BP goal as assessed by 24-hour ABPM. (change = Week 32 - Week 16)

change in 24-hour DBP following up titration to OM/AML/HCTZ 40/10/25 mg from OM/AML/HCTZ 40/10/12.5 mg in subjects not reaching BP goal as assessed by 24-hour ABPM. (change = Week 32 - Week 16)

change in 24-hour SBP following up titration to OM/AML/HCTZ 40/10/25 mg from OM/AML/HCTZ 40/10/12.5 mg in subjects not reaching BP goal as assessed by 24-hour ABPM. (change = Week 32 - Week 16)

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male or female aged 18 years or older.

- Mean trough SeBP of ≥ 160/100 mmHg (SeSBP of ≥ 160 mmHg and SeDBP ≥ 100 mmHg) at

Screening if not currently on antihypertensive medication (e. g. newly diagnosed subjects) and a mean 24-hour DBP of at least 85 mmHg with at least 30% of daytime DBP readings over 90 mmHg.

OR:

For subjects on monotherapy: mean trough SeBP of ≥ 150/95 mmHg (SeSBP of ≥ 150 mmHg and SeDBP ≥ 95 mmHg) at Screening and mean 24-hour DBP of at least 80 mmHg and with at least 30% of daytime DBP readings over 85 mmHg.

OR:

For subjects on any combination of antihypertensive medications that includes either HCTZ or AML for a duration of at least four weeks: mean trough SeBP of ≥ 140/90 mmHg (SeSBP of ≥ 140 mmHg and SeDBP ≥ 90 mmHg) at Screening and mean 24-hour DBP of at least 80 mmHg and with at least 30% of daytime DBP readings over 85 mmHg.

OR:

For subjects on any other combination of antihypertensive medications that includes neither HCTZ nor AML: mean trough SeSBP ≥ 160 mmHg, mean trough SeDBP ≥ 100mmHg, at the end of the taper-off period and a mean 24-hour DBP of at least 85 mmHg, assessed by 24-hour ABPM, with at least 30% of daytime DBP readings above 90 mmHg.

- 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 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.

- 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).

Esther Janssen, Phone: +33(0)146902451, Email: Esther.Janssen@mdsinc.com

Graz, Austria; Recruiting

Salzburg, Austria; Recruiting

Wien, Austria; Recruiting

Antwerpen, Belgium; Recruiting

Lauwe, Belgium; Recruiting

Leuven, Belgium; Recruiting

Liege, Belgium; Recruiting

Massemen, Belgium; Recruiting

Oostham, Belgium; Recruiting

Haskovo, Bulgaria; Recruiting

Pleven, Bulgaria; Recruiting

Plovdiv, Bulgaria; Recruiting

Sofia, Bulgaria; Recruiting

Varna, Bulgaria; Recruiting

Brno, Czech Republic; Recruiting

Bilovec, Czech Republic; Recruiting

Havlickuv Brod, Czech Republic; Recruiting

Hodonin, Czech Republic; Recruiting

Kladno, Czech Republic; Recruiting

Kolin, Czech Republic; Recruiting

Ostrava, Czech Republic; Recruiting

Ostrava-Vitkovice, Czech Republic; Recruiting

Praha, Czech Republic; Recruiting

Copenhagen, Denmark; Recruiting

Frederiksberg, Denmark; Recruiting

Naestved, Denmark; Recruiting

Roskilde, Denmark; Recruiting

Albi, France; Recruiting

Angers, France; Recruiting

Brest, France; Recruiting

Cambrai, France; Recruiting

Creteil, France; Recruiting

Dijon, France; Recruiting

Dinard, France; Recruiting

Lyon, France; Recruiting

Nancy, France; Recruiting

Pessac, France; Recruiting

Roubaix, France; Recruiting

Strasbourg, France; Recruiting

Tierce, France; Recruiting

Vandoeuvre, France; Recruiting

Villefranche de Rouergue, France; Recruiting

Berlin, Germany; Recruiting

Dresden, Germany; Recruiting

Einbeck, Germany; Recruiting

Hamburg, Germany; Recruiting

Magdeburg, Germany; Recruiting

Muenchen, Germany; Recruiting

Strasskirchen, Germany; Recruiting

Villingen-Schwenningen, Germany; Recruiting

Wermsdorf, Germany; Recruiting

Almere, Netherlands; Recruiting

Beek en Donk, Netherlands; Recruiting

Doetinchem, Netherlands; Recruiting

Groningen, Netherlands; Recruiting

Losser, Netherlands; Recruiting

Maastricht, Netherlands; Recruiting

Bytom, Poland; Recruiting

Gdansk, Poland; Recruiting

Katowice, Poland; Recruiting

Krakow, Poland; Recruiting

Piotrkow Trybunalski, Poland; Recruiting

Pulawy, Poland; Recruiting

Siemianowice Slaskie, Poland; Recruiting

Tarnow, Poland; Recruiting

Torun, Poland; Recruiting

Warszawa, Poland; Recruiting

Wroclaw, Poland; Recruiting

Brasov, Romania; Recruiting

Bucharest, Romania; Recruiting

Cluj-Napoca, Romania; Recruiting

Iasi, Romania; Recruiting

Oradea, Romania; Recruiting

Pitesti, Romania; Recruiting

Targoviste, Romania; Recruiting

Targu Mures, Romania; Recruiting

Timisoara, Romania; Recruiting

Moscow, Russian Federation; Recruiting

Ekaterinburg, Russian Federation; Recruiting

Novosibirsk, Russian Federation; Recruiting

Orenburg, Russian Federation; Recruiting

Ryazan, Russian Federation; Recruiting

Saratov, Russian Federation; Recruiting

Smolensk, Russian Federation; Recruiting

St. Petersburg, Russian Federation; Recruiting

Tomsk, Russian Federation; Recruiting

Yaroslavl, Russian Federation; Recruiting

Kosice, Slovakia; Recruiting

Banska Bysterica, Slovakia; Recruiting

Brastislava, Slovakia; Recruiting

Dolny Kubin, Slovakia; Recruiting

Presov, Slovakia; Recruiting

Sahy, Slovakia; Recruiting

Madrid, Spain; Recruiting

Alicante, Spain; Recruiting

Barcelona, Spain; Recruiting

Elche, Spain; Recruiting

Granada, Spain; Recruiting

Palma de Mallorca, Spain; Recruiting

Sevilla, Spain; Recruiting

Valencia, Spain; Recruiting

Vizcaya, Spain; Recruiting

Kiev, Ukraine; Recruiting

Dnipropetrovsk, Ukraine; Recruiting

Donetsk, Ukraine; Recruiting

Ivano-Frankivsk, Ukraine; Recruiting

Kharkiv, Ukraine; Recruiting

Lviv, Ukraine; Recruiting

Mykolayiv, Ukraine; Recruiting

Odesa, Ukraine; Recruiting

Simferopol, Ukraine; Recruiting

Uzhorod, Ukraine; Recruiting

Vinnytsya, Ukraine; Recruiting

Yalta, Ukraine; Recruiting

La Gineta, Albacete, Spain; Recruiting

La Roda, Albacete, Spain; Recruiting

Port de Sagunt, Valencia, Spain; Recruiting

Starting date: April 2009
Ending date: October 2010
Last updated: May 14, 2009