Essential hypertension MedDRA version: 9.1 Level: LLT Classification code 10020772 Term: Hypertension
Conditions
Sponsors
DAIICHI SANKYO EUROPE GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female aged 18 years or older. 2. 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. 3. Subject freely signs ICF after the nature of the study and the disclosure of his/her data has been explained. 4. 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 If a female becomes pregnant during the study, she has to be withdrawn immediately. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Female subjects of childbearing potential who are pregnant or lactating. 2. 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. 3. Subjects having a history of the following within the last six months: MI, unstable angina pectoris, percutaneous coronary intervention, heart failure, hypertensive encephalopathy, cerebrovascular accident (stroke), or transient ischaemic attack. 4. 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) • ALT > 3 times ULN • Gamma-glutamyltransferase (GGT) > 3 times ULN • Potassium above ULN (unless high value is due to haemolytic blood sample) 5. Subjects with secondary HTN of any aetiology such as renal disease, phaechromocytoma, or Cushing’s syndrome. 6. Subjects with contraindication to OM, AML, HCTZ, or any of the excipients. 7. Subjects with a mean SeSBP > 200 mmHg or SeDBP > 115 mmHg or bradycardia (heart rate 9.0%. Diabetics must have documentation of an HbA1c level within 6 months of the Screening Visit, or must have their
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The mean change in trough SeDBP from the randomisation visit (end of the OM/AML run-in period [Week 8]) to the end of the double-blind Period II (Week 16).;Main Objective: The primary objective (Period II, Week 8 to Week 16) is to demonstrate the additional antihypertensive efficacy for SeDBP gained by adding HCTZ 12.5 or 25 mg to the treatment regimen in subjects with moderate to severe HTN not adequately controlled on OM/AML 40/10 mg alone, at Week 16 (after 8 weeks of double-blind treatment) using conventional BP measurement.;Secondary Objective: Period II: 1. Evaluate antihypertensive efficacy for SeDBP of triple combination OM/AML/HCTZ 40/10/12.5 & 40/10/25 mg vs OM/AML 40/10 mg at Wk(week)12. 2. Evaluate antihypertensive efficacy for SeSBP of OM/AML/HCTZ 40/10/12.5 & 40/10/25mg vs OM/AML 40/10mg at Wk12&16. 3. Evaluate antihypertensive efficacy from baseline to Wk16 (see protocol p36). 4. Evaluate % no. subjects achieving BP goal (SeBP, see protocol p36) and % no. subjects achieving SeBP thresholds (see protocol p.36) at Wk12&16. 5. Evaluate safety & tolerability of triple combination therapy at Wk8-16. Period III&IV: 1. Evaluate antihypertensive efficacy of up titration of dose to 40/10/25mg in subjects not reaching BP goal on dose 40/10/12.5mg based on changes from Wk24-32 (see protocol p36). 2. Evaluate % no. subjects achieving BP goal & BP thresholds (defined point 4 above) at Wk32. 3. Evaluate safety & tolerability of triple combination therapy during Wk16-32. | — |
Countries
Austria, Bulgaria, Czech Republic, Denmark, France, Germany, Netherlands, Spain
Outcome results
None listed