The study is a global phase-3 randomized study, with a double-blind treatment period of 8 weeks.
- Conditions
- Essential HypertensionMedDRA version: 14.1Level: PTClassification code 10015488Term: Essential hypertensionSystem Organ Class: 10047065 - Vascular disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2011-000220-16-IT
- Lead Sponsor
- TAKEDA EUROPE RESEARCH & DEVELOPMENT CENTRE LTD
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 390
Main Criteria for Inclusion:
•The subject has grade 2-3 essential hypertension which is not adequately controlled as defined by mean, trough, sitting, clinic SBP:
–=160 to =180 mm Hg in subjects who have not received any antihypertensive medication in the 14 days prior to Visit 1.
–=150 to =170 mm Hg in subjects taking 1 antihypertensive medication at Visit 1.
–=140 to =160 mm Hg in subjects taking 2 antihypertensive medications at Visit 1.
•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 relevant for precluding entry in to the study in this hypertensive population.
•The subject is willing to discontinue current antihypertensive medications.
•The subject must have a post-placebo run-in, 24-hour mean SBP by ABPM of 140-175 mm Hg inclusive, and a sitting clinic SBP measurement of 160 to 190 mm Hg inclusive (determined by the mean of 3 sitting, trough, measurements on Day -29) to qualify for entry in to the 4 week single-blind TAK-491 40 mg monotherapy treatment testing period.
•The subject does not achieve target blood pressure (defined as clinic SBP =140 mm Hg as determined by the mean of 3 sitting, trough, measurements) following 4 weeks single-blind treatment with TAK-491 40 mg monotherapy at Day -1, prior to randomization to double-blind treatment.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 312
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 78
Main Criteria for Exclusion:
•The subject has clinic DBP >110 mm Hg.
•The subject’s 3 SBP measurements at screening differ by more than 15 mm Hg (confirmed by a second set of three measurements).
•The subject is currently treated with more than 2 antihypertensive medications.
•The subject has secondary hypertension of any etiology (eg, renovascular disease, pheochromocytoma, Cushing’s syndrome).
•The subject has any history of myocardial infarction, heart failure, unstable angina, coronary artery bypass graft, percutaneous coronary intervention, hypertensive encephalopathy, cerebrovascular accident, persistent or permanent atrial fibrillation or transient ischemic attack.
•The subject has clinically significant cardiac conduction defects (eg, third-degree atrioventricular block, sick sinus syndrome).
•The subject has severe renal dysfunction or disease [based on estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 at screening].
•The subject has poorly-controlled type 1 or 2 diabetes mellitus (hemoglobin A1c [HbA1c] >8.5%) at Screening.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy and safety of the fixed dose combinations of TAK-491 plus chlorthalidone (40/12.5 mg and 40/25 mg) in subjects with grades 2 or 3 essential hypertension who do not reach target blood pressure following 4 weeks of treatment with TAK-491 40 mg monotherapy.;Secondary Objective: NA;Primary end point(s): Primary Endpoint<br>•Change from baseline to Week 8 in trough, sitting, clinic SBP.;Timepoint(s) of evaluation of this end point: week 8
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Secondary Endpoints<br>•Change from baseline to Week 8 in trough, sitting, clinic DBP.<br>•Change from baseline to Week 8 in trough (22 to 24 hours after dosing) SBP as measured by ABPM.<br>•Change from baseline to Week 8 in trough DBP as measured by ABPM.<br>•Change from baseline to week 8 in the following ABPM parameters:<br>–24-hour mean SBP and DBP.<br>–Mean daytime (6 AM to 10 PM) SBP and DBP.<br>–Mean nighttime (12 AM to 6 AM) SBP and DBP.<br>–Mean SBP and DBP at 0 to 12 hours after dosing.<br>•Proportion of subjects who achieve target blood pressure at Week 8 as defined by the following:<br>a)Trough, sitting clinic SBP <140 mm Hg (or <130 mm Hg for patients with diabetes or CKD).<br>b)Trough, sitting, clinic DBP <90 mm Hg (or <80 mm Hg for patients with diabetes or CKD).<br>c)Achieving both trough, sitting clinic SBP and DBP targets above.;Timepoint(s) of evaluation of this end point: week 8