Comparison in Japan T80/A5 (Telmisartan 80 mg and Amlodipine 5 mg) and T40/A5 (Telmisartan 40 mg and Amlodipine 5 mg)

Study Overview
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Brief Summary
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Blood pressure in hypertensive patients is rarely controlled to an optimal level by one drug alone, often a combination of two or more drugs is essential to achieve a sufficient antihypertensive effect. Therefore in Japanese Society of Hypertension (JSH) 2009 combination therapy is recommended. In JSH 2009 it is advised to start the combination therapy at a low dose, and to increase the dosage when the antihypertensive effect is not sufficient. In the Japanese long-term safety study, 259 patients received the T40/A5 mg fixed-dose combination (FDC), and after 6 weeks treatment 48 patients of them could not control their blood pressure (DBP =90) (U09-2494-01). For those patients who cannot control their blood pressure with T40/A5 mg FDC, a switch to a higher dose such as T80/A5 mg is recommended. In the overseas 4x4 factorial design trial, a clinically meaningful difference of the blood pressure lowering effect between T80/A5 mg free combination and T40/A5 mg free combination was shown (U07-3503-02). But the sponsor has no data that verifies this difference in Japanese patients. Thus, this clinical trial is being conducted to investigate the antihypertensive effect and safety of high dose T80/A5 mg FDC compared with low dose T40/A5 mg FDC in Japanese patients with essential hypertension. In this trial, a multi-centre, randomised, double-blind, double-dummy, active-controlled, parallel group comparison method is employed.

Official Title
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An Eight-week Randomised Double-blind Study to Compare the Efficacy and Safety of Telmisartan 80mg Plus Amlodipine 5 mg Fixed-dose Combination vs. Telmisartan 40 mg Plus Amlodipine 5 mg Fixed-dose Combination in Patients With Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: 40 mg telmisartan
* Drug: 5 mg amlodipine
* Drug: 5 mg amlodipine
* Drug: 80 mg telmisartan


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Essential hypertensive patients If already taking antihypertensive drugs, mean seated diastolic blood pressure (DBP) must be >=90 and >=114 mmHg If not taking any antihypertensive drugs, mean seated DBP must be >=95 and >=114 mmHg Able to stop all current antihypertensive drugs without risk to the patient based on the investigators opinion. Exclusion criteria: Patients taking 3 or more antihypertensive drugs at signing the informed consent form Patients with known or suspected secondary hypertension Patients with clinically relevant cardiac arrhythmia Congestive heart failure with New York Heart Association (NYHA) functional class III-IV Patients with recent cardiovascular events Patients with a history of stroke or transient ischaemic attack within last 6 months before signing the informed consent form Patients with a history of sudden deterioration of renal function with angiotensin II receptor blockers (ARBs) or angiotensin converting enzyme (ACE) inhibitors; or patients with post-renal transplant or post-nephrectomy Patients who have previously experienced characteristic symptoms of angioedema (such as facial, tongue, pharyngeal, or laryngeal swelling with dyspnea) during treatment with ARBs or ACE inhibitors Patients with known hypersensitivity to any component of the investigational product, or a known hypersensitivity to dihydropyridine-derived drugs Patients with hepatic and/or renal dysfunction Pre-menopausal women who are nursing or pregnant

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 80mg telmisartan and 5mg amlodipine FDC<br>once daily | Drug: 5 mg amlodipine<br>* once daily<br>Drug: 80 mg telmisartan<br>* once daily<br>|
| Active Comparator: 40mg telmisartan and 5mg amlodipine FDC<br>once daily | Drug: 40 mg telmisartan<br>* once daily<br>Drug: 5 mg amlodipine<br>* once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction From the Reference Baseline in Mean Seated Diastolic Blood Pressure (DBP) at Trough | Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined At trough: 24-hour post-dosing | Reference baseline, 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction From the Reference Baseline in Mean Seated Systolic Blood Pressure (SBP) at Trough | Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined At trough: 24-hour post-dosing | Reference baseline, 8 weeks | 
| Changes From the Reference Baseline in the 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Mean (Relative to Dose Time) for DBP | Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined | Reference baseline, 8 weeks | 
| Changes From the Reference Baseline in the 24-hour ABPM Mean (Relative to Dose Time) for SBP | Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined | Reference baseline, 8 weeks | 
| Changes From the Pseudo-baseline in the 24-hour ABPM Mean (Relative to Dose Time) for DBP | Pseudo-baseline: Status of patients after the 6-week open-label run-in period with telmisartan monotherapy, where patients' eligibility to enter the double-blind treatment period was examined | Pseudo-baseline, 14 weeks | 
| Changes From the Pseudo-baseline in the 24-hour ABPM Mean (Relative to Dose Time) for SBP | Pseudo-baseline: Status of patients after the 6-week open-label run-in period with telmisartan monotherapy, where patients' eligibility to enter the double-blind treatment period was examined | Pseudo-baseline, 14 weeks | 
| Changes From the Reference Baseline in DBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined | Reference baseline, 8 weeks | 
| Changes From the Reference Baseline in SBP Hourly Mean Over the 24-hour Dosing Interval as Measured by ABPM | Reference baseline: Status of patients after the 12-week open-label run-in period with telmisartan monotherapy followed by 40 mg telmisartan and 5 mg amlodipine combination therapy, where patients' eligibility to enter the double-blind treatment period was examined | Reference baseline, 8 weeks | 
| Seated DBP Control Rate at Trough | DBP control rate: The rate of patients with controlled seated DBP at trough of less than 90 mmHg after the 8-week double-blind period At trough: 24-hour post-dosing | 8 weeks | 
| Seated SBP Control Rate at Trough | SBP control rate: The rate of patients with controlled seated DBP at trough of less than 140 mmHg after the 8-week double-blind period At trough: 24-hour post-dosing | 8 weeks | 
| Seated DBP Response Rate at Trough | DBP response rate: The rate of patients who achieved an adequate response in seated DBP at trough (<90 mmHg and/or reduction from reference baseline >=10 mmHg) after the 8-week double-blind period At trough: 24-hour post-dosing | 8 weeks | 
| Seated SBP Response Rate at Trough | SBP response rate: The rate of patients who achieved an adequate response in seated SBP at trough (<140 mmHg and/or reduction from reference baseline >=20 mmHg) after the 8-week double-blind period At trough: 24-hour post-dosing | 8 weeks | 
| Seated Blood Pressure (BP) Normalisation at Trough | Seated blood pressure (BP) normalisation: The numbers of patients whose blood pressure was within normalisation criterion in terms of seated blood pressure after the 8-week double-blind period At trough: 24-hour post-dosing | 8 weeks |