According to the World Health Organization, hypertension (high blood pressure) is the most common attributable cause of preventable death in developed nations. When uncontrolled, hypertension is associated with greatly increased risk of cardiovascular disease, cerebrovascular disease, and renal failure. MedDRA version: 9.1 Level: LLT Classification code 10015488 Term: Essential hypertension
Conditions
Interventions
Product Name: TAK-491 20 mg tablets
Pharmaceutical Form: Tablet
CAS Number: 863031-24-7
Current Sponsor code: TAK-491
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number
Sponsors
Takeda Global Research & Development Centre (Europe) Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - The subject has essential hypertension (defined as SBP between 150 and 180 mmHg, inclusive, at Randomization). - The subject is a man or non pregnant woman, aged 18 years or older. - The subject is capable of understanding and complying with protocol requirements. - The subject or the subject’s legally acceptable representative signs a written, informed consent form prior to the initiation of any study procedures. - A female subject of childbearing potential who is sexually active agrees to use adequate contraception from screening throughout the duration of the study. Women not of child-bearing potential are defined as those who have been surgically sterilized (hysterectomy, oophorectomy, tubal ligation) or who are postmenopausal (defined as at least 2 years since last regular menses). - The subject has clinical laboratory evaluations (including clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory at Screening or the results are deemed not clinically significant for inclusion into this study by the investigator. - The subject is willing to discontinue current antihypertensive medications at Screening Day -21. If the subject is on amlodipine prior to screening, the subject is willing to discontinue this medication at Screening Day -28. 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: - The subject has an SBP greater than 180 mmHg or DBP greater than 114 mmHg at Randomization. - The subject is taking or expected to take an excluded medication as described in the Excluded Medications section. - The subject has known hypersensitivity to ARBs and/or ACE inhibitors. - The subject has a recent history (within the last 6 month) of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack. - The subject has clinically significant cardiac conduction defects (eg, third-degree atrioventricular block, left bundle branch block, sick sinus syndrome, atrial fibrillation or flutter). - The subject has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease. - The subject has secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing’s syndrome). - The subject is noncompliant (less than 70% or greater than 130%) with study medication during placebo run-in period. - The subject has severe renal dysfunction or disease (based on calculated creatinine clearance 8.0%) or is taking insulin. - The subject has hyperkalemia as defined by the central laboratory normal reference range at Screening. - The subject has an upper arm circumference less than 24 cm or greater than 42 cm. - The subject works night (third) shift (defined as 11 PM to 7 AM). - The subject has an alanine aminotransferase (ALT) level at Screening of greater than 2.5 times the upper limit of normal (ULN), active liver disease, or jaundice. - The subject is unwilling or unable to comply with the protocol or scheduled appointments. - The subject is unable to understand verbal or written English or any other language for which a certified translation of the approved informed consent is available. - The subject is a study site employee, or is an immediate family member (ie, spouse, parent, child, and sibling) of a study site employee who is involved in conduct of this study. - If female, the subject is pregnant, intends to become pregnant during the course of the study, or is lactating. - The subject currently is participating in another investigational study or has participated in an investigational study within 30 days prior to Screening. - The subject has any other serious disease or condition at Screening or Randomization that would compromise subject safety, might affect life expectancy, or make it difficult to successfully manage and follow the subject according to the protocol. - The subject has been randomized in a previous TAK-491 study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the change in clinic SBP (systolic blood pressure) in response to TAK-491 compared with ramipril for 6 months in subjects with essential hypertension.;Secondary Objective: The secondary objectives of this study are: - To evaluate the change in clinic diastolic blood pressure (DBP), in response to TAK-491 compared to ramipril. - To evaluate the change in DBP and SBP by ABPM, in response to TAK-491 compared to ramipril. - To evaluate the proportion of subjects who achieve the following response criteria at month 6: d) Clinic DBP <90 mm Hg. e) Clinic SBP <140 mm Hg. f) Clinic DBP <90 mm Hg and clinic SBP <140 mm Hg. - To evaluate safety and tolerability of TAK-491 (AEs, safety laboratory tests, vital signs, and ECG). - To compare the safety profile of TAK-491 with that of ramipril. ;Primary end point(s): The primary endpoint is the change from baseline in the sitting trough clinic SBP. | — |
Countries
Bulgaria, Estonia, Finland, Germany, Netherlands, Sweden
Outcome results
None listed