Compare Efficacy and Safety of Telmisartan/Hydrochlorothiazide With Telmisartan/Hydrochlorothiazide Plus Amlodipine

Study Overview
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Brief Summary
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This is a multi-centre, randomised, double-blind, active-controlled, parallel-group comparative trial to compare the fixed dose combination (FDC) of telmisartan 80 mg + hydrochlorothiazide 12.5 mg and amlodipine 5 mg (T80/A5/H12.5 mg) to telmisartan 80 mg+ hydrochlorothiazide 12.5 mg (T80/H12.5 mg) in blood pressure lowering effect at week 8, the end of the double-blind period in essential hypertensive patients who fail to respond adequately to telmisartan 80 mg+ hydrochlorothiazide 12.5 mg. Patients are assigned to one of the two groups after a 6-week open-label run-in period taking T80/H12.5 mg. In addition the long-term safety of telmisartan 80 mg+ amlodipine 5 mg+ hydrochlorothiazide 12.5 mg will be evaluated in a 52-week extension period. In the 52-week open label extension period patients who are assigned to the T80/A5/H12.5 mg group continue the T80/A5/H12.5 mg therapy, and patients who are assigned to the T80/ /H12.5 mg group change to the T80/A5/H12.5 mg therapy.

Official Title
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An Eight-week Randomised Double-blind Study to Compare the Efficacy and Safety of Telmisartan 80 mg and Amlodipine 5 mg and Hydrochlorothiazide 12.5 mg vs. Telmisartan 80 mg and Hydrochlorothiazide 12.5 mg in Patients With Hypertension Who Fail to Respond Adequately to Treatment With Telmisartan 80 mg and Hydrochlorothiazide 12.5 mg, Followed by a 52 Weeks Extension Study to Assess Long Term Safety of Telmisartan 80 mg and Amlodipine 5 mg and Hydrochlorothiazide 12.5 mg

Conditions
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Hypertension

Intervention / Treatment
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* Drug: placebo
* Drug: telmisartan + HCTZ
* Drug: telmisartan + HCTZ
* Drug: amlodipine


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Essential hypertensive patients who have already taking 2 or 3 antihypertensive drugs and mean seated diastolic blood pressure (DBP) must be >=90 and <=114 mmHg and mean seated systolic blood pressure (SBP) must be =<200 mmHg Able to stop all current antihypertensive drugs (other than study medication) from Visit 1b through the end of the trial without risk to the patient based on the investigator's opinion Age 20 years or older Exclusion criteria: 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 recent stroke events Patients with a history of sudden deterioration of renal function with angiotensin II receptor blockers or angiotensin converting enzyme inhibitors; or patients with post-renal transplant or post-nephrectomy 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
Maximum Age: 100 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: telmisartan + HCTZ + amlodipine<br>telmisartan 80 mg + hydrochlorothiazide (HCTZ) 12.5 mg fixed dose combination (FDC) and amlodipine 5 mg capsule (after the 8-week double-blind period, patients will continue the 52-week open label extension period taking 1 telmisartan 80 mg and hydrochlorothiazide 12.5 FDC tablet and 1 amlodipine 5 mg tablet) | Drug: telmisartan + HCTZ<br>* FDC tablet<br>Drug: amlodipine<br>* capsule<br>|
| Active Comparator: telmisartan + HCTZ + placebo<br>telmisartan 80 mg + HCTZ FDC tablet and placebo matching amlodipine 5 mg capsule (after the 8-week double-blind period, patients will continue the 52-week open label extension period taking 1 telmisartan 80 mg and hydrochlorothiazide 12.5 FDC tablet and 1 amlodipine 5 mg tablet) | Drug: placebo<br>* placebo matching amlodipine capsule<br>Drug: telmisartan + HCTZ<br>* FDC tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Seated DBP at Trough After 8 Weeks of the Double-blind Period. | Change from baseline in mean seated diastolic blood pressure (DBP) at trough (24-hour post dosing) after 8 weeks of the double-blind period. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'. | baseline and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mean Seated SBP at Trough After 52 Weeks of the Extension Period. | Change from baseline in mean seated systolic blood pressure at trough after 52 weeks of the extension period. Note, week 52 of the extension period corresponds to 60 weeks after the reference baseline. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'. | Reference baseline (week 0) and week 60 (end of extension period) | 
| Change From Baseline in Mean Seated SBP at Trough After 8 Weeks of the Double-blind Period. | Change from baseline in mean seated systolic blood pressure (SBP) at trough after 8 weeks of the double-blind period. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'. | baseline and 8 weeks | 
| The Percentage of Patients With DBP<90 mmHg and SBP<140 mmHg Blood Pressure at Trough After 8 Weeks of Double-blind Period. | The percentage of patients with DBP<90 mmHg and SBP<140 mmHg as seated blood pressure at trough after 8 weeks of the double-blind period. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'. | Double-blind and 8 weeks | 
| The Number of Patients With DBP<90 mmHg and SBP<140 mmHg Blood Pressure at Trough After 52 Weeks of Extension Period. | The number of patients with DBP<90 mmHg and SBP<140 mmHg as seated blood pressure at trough after 52 weeks of the extension period. Note, week 52 of the extension period corresponds to 60 weeks after the reference baseline. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'. | Reference baseline (week 0) and week 60 (end of extension period) | 
| Change From Baseline in Mean DBP Pressure at Trough After 52 Weeks of the Extension Period. | Change from baseline in mean seated diastolic blood pressure at trough after 52 weeks of the extension period. Note, week 52 of the extension period corresponds to 60 weeks after the reference baseline. The results are presented as 'change' rather than 'reduction' i.e., reductions are expressed with negative values'. The 'adjusted mean' is shown as 'mean'. | Reference baseline (week 0) and week 60 (end of extension period) |