Study to Evaluate the Efficacy and Safety of TEL/AML/CTD in Elderly Patients With Essential Hypertension

Study Overview
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Brief Summary
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This study is to compare the efficacy and safety of Telmisartan, Amlodipine, and Chlorthalidone Fixed-Dose Combination and Telmisartan, Amlodipine, and Hydrochlorothiazide in Elderly Patients with Essential Hypertension Uncontrolled by Telmisartan and Amlodipine Combinations

Detailed Description
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This is a Phase IV, Randomized, Open-label, Superiority, Comparative study evaluating the efficacy and safety of Telmisartan, Amlodipine, and Chlorthalidone Fixed-Dose Combination) versus Telmisartan, Amlodipine, and Hydrochlorothiazide in eledrly patient with essential hypertension uncontrolled by Telmisartan and Amlodipine Combinations.

Official Title
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An Open-Label, Superiority, Randomized, Comparative Study to Evaluate the Efficacy and Safety of Telmisartan, Amlodipine, and Chlorthalidone Fixed-Dose Combination Versus Telmisartan, Amlodipine, and Hydrochlorothiazide in Elderly Patients With Essential Hypertension Uncontrolled by Telmisartan and Amlodipine Combinations

Conditions
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Essential Hypertension

Intervention / Treatment
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* Drug: Telmisartan/Amlodipine/Chlorthalidone 40/5/12.5 mg
* Drug: Telmisartan/Amlodipine/Hydrochlorothiazide 40/5/25 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Aged ≥ 65 with essential hypertension Patient with uncontrolled essential hypertension at screening If already taking antihypertensive drugs, mean sitting systolic blood pressure (MSSBP) must be 140 mmHg ≤ MSSBP < 200 mmHg If not taking any antihypertensive drugs at least 4 weeks, mean sitting systolic blood pressure (MSSBP) must be 160 mmHg ≤ MSSBP < 200 mmHg Medication compliance of investigational product (Run-in) > 70 % Patient who has measured nighttime blood pressure more than 7 times from the night before the randomized date to the morning of the day of the randomized date (22:00 5:59) Patient with uncontrolled essential hypertension at Visit 2 140 mmHg ≤ MSSBP < 200 mmHg Exclusion Criteria: Patient who has secondary hypertension or suspected of secondary hypertension Patient who has orthostatic hypotension with symptoms Patient who has severe hypotension and severe heart disease (NYHA class III IV) Patient who has been diagnosed with or treated with the following diseases within the last 6 months judged by the investigator to be clinically significant Patient who has ischemic heart disease, peripheral vascular disease, percutaneous transluminal coronary angioplasty, or coronary artery bypass surgery Patient who has clinically significant ventricular tachycardia, atrial fibrillation, atrial flutter, or other arrhythmia judged clinically significant by the investigator Patient who has hypertrophic obstructive cardiomyopathy, severe obstructive coronary artery disease, aortic stenosis, aortic valve hemodynamically significant or mitral valve stenosis/reflux Patient who has severe cerebrovascular disease Known moderate or malignant retinopathy Patient who has sleep disorders or apnea during sleep Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of investigational products Patient who has untreated addison's disease, symptomatic hyperuricemia, hyperparathyroidism, sympathetic nerve resection, shock patients Patient with anuria History of malignant tumor Patient with any chronic inflammation disease needed to chronic inflammation therapy Patient with mental defects that may interfere with participation in clinical trials Patient who has history of drug allergic reactions Patient who has angioedema related to ACE inhibitors, ARBs or diuretics Patient who has galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorpiton. Known hypersensitivity to components of the investigational product Patient who is unable to stop taking prohibited drugs Test results showing the following values at screening The change of MSSBP ≥ 20 mmHg and MSDBP ≥ 10 mmHg on target arm between 1st and 2nd measurements Hepatic or renal dysfunction as defined by the following laboratory parameters (eGFR < 30 mL/min/1.73m2, Serum creatinine ≥ 3 mg/dL, AST/ALT > UNL X 3) Hypokalemia (Serum K < 3.0 mmol/L) or hyperkalemia (Serum K > 5.5 mmol/L), hyponatremia (Serum Na < 132.0 mmol/L) or uncontrolled diabetes (HbA1c > 9.0%) Pregnant or lactating women Patient who is unable to maintain proper night sleep History of drug or alcohol dependency within 1 year prior to screening Malnutrition, starvation, debilitating factors, A person who is being forcibly detained for the treatment of mental or physical Administration of other investigational products within 3 months prior to screening. An impossible one who participates in clinical trial by investigator's decision

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telmisartan/Amlodipine/Chlorthalidonea 40/5/12.5 mg<br>Telmisartan/Amlodipine/Chlorthalidonea 40/5/12.5 mg will be orally administered during the study period | Drug: Telmisartan/Amlodipine/Chlorthalidone 40/5/12.5 mg<br>* PO, Once daily(QD), 8 weeks and 26 weeks if applicable<br>* Other names: Truset 40/5/12.5mg;|
| Active Comparator: Telmisartan/Amlodipine/Hydrochlorothiazide 40/5/25 mg<br>Telmisartan/Amlodipine 40/5 mg and Hydrochlorothiazide 25 mg will be orally administered each during study period | Drug: Telmisartan/Amlodipine/Hydrochlorothiazide 40/5/25 mg<br>* PO, Once daily(QD), 8 weeks and 26 weeks if applicable<br>* Other names: Twynsta 40/5 mg, Dichlozid 25 mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Systolic Blood Pressure (MSBP) in nighttime | To evaluate change from baseline in nighttime Mean Systolic Blood Pressure (MSBP) measured by Ambulatory Blood Pressure Monitoring at Week 8 | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Systolic Blood Pressure (MSBP) in nighttime | To evaluate change from baseline in nighttime Mean Systolic Blood Pressure (MSBP) measured by Ambulatory Blood Pressure Monitoring at Week 26 if applicable | Week 26 if applicable | 
| Mean Diastolic Blood Pressure (MDBP) in nighttime | To evaluate change from baseline in nighttime Mean Diastolic Blood Pressure (MDBP) measured by Ambulatory Blood Pressure Monitoring at Week 8 and Week 26 if applicable | Week 8 and Week 26 if applicable | 
| Mean Systolic Blood Pressure (MSBP)/Mean Diastolic Blood Pressure (MDBP) in daytime | To evaluate change from baseline in daytime Mean Systolic Blood Pressure (MSBP)/Mean Diastolic Blood Pressure (MDBP) measured by Ambulatory Blood Pressure Monitoring at Week 8 and Week 26 if applicable | Week 8 and Week 26 if applicable | 
| 24-hour Mean Systolic Blood Pressure (MSBP)/Mean Diastolic Blood Pressure (MDBP) | To evaluate change from baseline in 24-hour Mean Systolic Blood Pressure (MSBP)/Mean Diastolic Blood Pressure (MDBP) measured by Ambulatory Blood Pressure Monitoring at Week 8 and Week 26 if applicable | Week 8 and Week 26 if applicable | 
| Patients Achieving in nighttime Mean Systolic Blood Pressure (MSBP) | To evaluate the percentage of patients who reached the treatment goal for nighttime Mean Systolic Blood Pressure (MSBP) (<110/65mmHg) measured by Ambulatory Blood Pressure Monitoring at Week 8 | Week 8 | 
| Mean Sitting Systolic Blood Pressure (MSSBP)/ Mean Sitting Diastolic Blood Pressure (MSDBP) | To evaluate change from baseline in Mean Sitting Systolic Blood Pressure (MSSBP)/ Mean Sitting Diastolic Blood Pressure (MSDBP) measured by the Institution at Week 4, Week 8 and Week 26 if applicable | Week 4, Week 8 and Week 26 if applicable | 
| Patients Achieving in Mean Sitting Systolic Blood Pressure (MSSBP) | - To evaluate the percentage of patients who reached the treatment goal for Mean Sitting Blood Pressure (MSBP) < 140/90 mmHg measured by the Institution at Week 4, Week 8 and Week 26 if applicable | Week 4, Week 8 and Week 26 if applicable | 
| Percentage of patients with decreased Mean Sitting Systolic Blood Pressure (MSSBP) and Mean Sitting Diastolic Blood Pressure (MSDBP). | To evaluate the percentage of subjects with a Mean Sitting Systolic Blood Pressure (MSSBP) decrease of ≥20mmHg and a Mean Sitting Diastolic Blood Pressure (MSDBP) decrease of ≥10mmHg at Week 4, Week 8 and Week 26 if applicable | Week 4, Week 8 and Week 26 if applicable | 
| T/P ratio | To evaluate the T/P ratio for systolic/diastolic blood pressure measured by Ambulatory Blood Pressure Monitoring at Week 8 and Week 26 if applicable | Week 8 and Week 26 if applicable | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Telmisartan/Amlodipine/Chlorthalidone Fixed-Dose Combination