TAK-491CLD is being evaluated to treat essential hypertension MedDRA version: 9.1 Level: LLT Classification code 10015488 Term: Essential hypertension
Conditions
Interventions
Product Name: Azilsartan medoxomil plus chlorthalidone fixed-dose combination
Product Code: TAK-491CLD
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Azilsartan medoxomil
CAS Number: 86
Sponsors
Takeda Global Research & Development Centre (Europe) Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subject eligibility is determined according to the following criteria: 1. The subject is treated with antihypertensive therapy and has a post-washout mean sitting clinic SBP =160 and =190 mm Hg on Day 1 or the subject has not received antihypertensive treatment within 14 days prior to Screening and has a mean sitting clinic SBP =160 and =190 mm Hg at the Screening Visit and on Day 1. 2. The subject is a man or woman aged 18 years or older. 3. A female subject of childbearing potential who is sexually active agrees to routinely use adequate contraception from Screening through 30 days after the last study drug dose. NOTE: Women NOT of childbearing potential are defined as those who have been surgically sterilized (hysterectomy, bilateral oophorectomy, tubal ligation [performed more than 1 year prior to Screening) or who are postmenopausal (defined as at least 1 year since last regular menses). Acceptable methods of contraception are defined in Section 9.1.9 Contraception and Pregnancy Avoidance Procedure. 4. The subject is capable of understanding and willing to comply with protocol requirements. 5. The subject or the subject’s legally acceptable representative signs an informed consent form prior to the initiation of any study procedures. 6. The subject has clinical laboratory test results (clinical chemistry, hematology, and complete urinalysis) within the reference range for the testing laboratory or the investigator does not consider the results to be clinically significant. 7. The subject is willing to discontinue current antihypertensive medications up to 3 weeks before enrollment. 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: Any subject who meets any of the following criteria will not qualify for entry into the study: 1. The subject has a mean clinic DBP (sitting, trough) >119 mm Hg on Day 1. 2. The subject has secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing’s syndrome). 3. The subject has a recent history (within the last 6 months) of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack. 4. The subject has clinically significant cardiac conduction defects (ie, third-degree atrioventricular block, sick sinus syndrome). 5. The subject has hemodynamically significant left ventricular outflow obstruction due to aortic valvular disease. 6. The subject has severe renal dysfunction or disease [based on estimated glomerular filtration rate (GFR) 8.0%) at Screening. 10. The subject has hypokalemia or hyperkalemia (defined as serum potassium outside of the normal reference range of the central laboratory) at Screening. 11. The subject has an alanine aminotransferase or aspartate aminotransferase level of greater than 2.5 times the upper limit of normal, active liver disease, or jaundice at Screening. 12. The subject has any other known serious disease or condition that would compromise safety, might affect life expectancy, or make it difficult to successfully manage and follow the subject according to the protocol. 13. The subject has known hypersensitivity to ARBs or thiazide-type diuretics or other sulfonamide-derived compounds. 14. The subject has been randomized/enrolled in a previous TAK-491 or TAK-491CLD study. 15. The subject currently is participating in another investigational study or has received any investigational compound within 30 days prior to Screening. Note: This criterion does not apply to subjects who began participation in another TAK-491 or TAK-491 CLD study but were not randomized, nor does it apply to subjects who participated in observational studies that lacked an intervention or invasive procedure. 16. If female, the subject is pregnant or lactating or intending to become pregnant before or during study participation, or within 30 days after last study drug dose. 17. The subject is a study site employee, or is an immediate family member (ie, spouse, parent, child, sibling) of a study site employee who is involved in conduct of this study. 18. The subject has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse within the past 2 years. 19. The subject is taking or expected to take any excluded medication (see the Excluded Medications and Treatments section).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the long-term safety and tolerability of the TAK-491CLD FDC in comparison to the OLM/HCTZ FDC in subjects with essential hypertension.;Secondary Objective: The secondary objective of this study is to evaluate the long-term efficacy of TAK-491CLD FDC in comparison to OLM/HCTZ FDC when using a titration to target treatment approach.;Primary end point(s): Primary endpoint: Percentage of subjects with at least one adverse events (AE) from Week 0 to Week 52. Secondary Endpoint Percentage of subjects with creatinine elevations from baseline greater than 50% and greater than the upper limit of normal (ULN) from Week 0 to Week 52. Other safety endpoints include: clinical safety laboratory tests, 12-lead electrocardiogram (ECG) findings, vital signs (including orthostatic vital signs). | — |
Countries
Austria, Germany, United Kingdom
Outcome results
None listed