Essential hypertension MedDRA version: 9.1 Level: LLT Classification code 10020772 Term: Hypertension
Conditions
Interventions
Product Name: OM/AML/HCTZ 40/10/25 mg and CS-8635
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: olmesartan medoxomil
CAS Number: 144689-63-4
Other descriptive name: OM
Concentration uni
Sponsors
DAIICHI SANKYO EUROPE GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female subjects aged 18 years or older. 2. Subjects with mean trough SeBP = 160/100 mmHg (SeSBP = 160 mmHg and 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 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. 3. Subjects freely sign 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]). 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 If a female becomes pregnant during the study, she has to be withdrawn from the study immediately.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, haematologic or, neurologic, 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-glutamyl transferase (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, phaeochromocytoma, or Cushing’s syndrome. 6. Subjects with contraindication to OM, AML, HCTZ, or any of the excipients. 7. Newly diagnosed subjects with a mean trough SeSBP > 200 mmHg or mean trough SeDBP > 115 mmHg or any subject with bradycardia (heart rate 145 mmHg or mean trough SeDBP > 95 mmHg while taking three antihypertensive medications. 10. Subjects with a mean trough SeSBP > 160 mmHg or mean trough SeDBP > 100 mmHg while taking two antihypertensive medications. 11. Subjects with a mean trough SeSBP > 180 mmHg or mean trough SeDBP > 110 mmHg while taking one antihypertensive medication. 12. Subjects with ECG evidence of 2nd or 3rd degree atrio-ventricular (AV) block, atrial fibrillation, or other cardiac arrhythmia (requiring treatment). 13. 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. 14. 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 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. 18. Subjects with a history of a wasting disease (e.g. cancer), autoimmune diseases, connective tissue diseases, major allergies or angioneurotic oedema. 19. Subjects who require or are taking any concomitant medication w
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main objective of this study is to demonstrate that OM/AML/HCTZ triple combinations are more efficacious in lowering SeDBP than corresponding dual combinations of OM/AML after 10 weeks of double blind treatment.;Secondary Objective: P(Period) I-II: 1) Evaluate AH (antihypertensive) efficacy for SeSBP lowering at various doses OM/AML/HCTZ compared to OM/AML after 4, 6, 8 &10 wks (weeks) DB (double-blind treatment). 2) Evaluate AH efficacy for SeDBP lowering with admin various doses OM/AML/HCTZ compared to OM/AML after 4, 6&8 wks DB. 3) Evaluate % subjects achieving BP goal (see protocol p.38) during DB. 4) Evaluate % subjects achieving SeBP thresholds specified protocol. p.38, after 4,6,8 & 10 wk of DB. 5) Evaluate patient questionnaires results at baseline & wk10. P III-VI: 1) Gain long-term efficacy & safety experience with admin of OM/AML/HCTZ while treating subjects to BP goal (see protocol p.38). 2) Evaluate % subjects achieving BP goal & thresholds for triple combination therapies (see protocol p.38). 3) Evaluate benefit up-titration of triple therapies. 4) Evaluate benefit of triple therapy (P VI), see protocol p.39. 5) Evaluate questionnaire results at wk 26&54.;Primary end point(s): The change in mean trough SeDBP from baseline to the end of Week 10 (end of Period II). | — |
Countries
Bulgaria, Czech Republic, Denmark, Germany, Italy, Latvia, Netherlands, Spain
Outcome results
None listed