Telmisartan (Micardis) and Amlodipine (Norvasc) - Factorial Design Study for the Treatment of Hypertension

Study Overview
=================
Brief Summary
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To demonstrate that Micardis and Norvasc when used together are more effective at lowering blood pre ssure.

Official Title
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A Randomized, Double-blind, Double-dummy, Placebo-controlled, 4x4 Factorial Design Trial to Evaluate Telmisartan 20, 40 and 80 mg Tablets in Combination With Amlodipine 2.5, 5 and 10 mg Capsules After Eight Weeks of Treatment in Patients With Stage I or II Hypertension, With an ABPM Sub-study

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Amlodipine 5 mg
* Drug: Placebo
* Drug: Telmisartan 20 mg
* Drug: Telmisartan 40 mg
* Drug: Amlodipine 10 mg
* Drug: Telmisartan 20 mg
* Drug: Telmisartan 80 mg
* Drug: Amlodipine 10 mg
* Drug: Telmisartan 20 mg
* Drug: Amlodipine 5 mg
* Drug: Amlodipine 5 mg
* Drug: Telmisartan 20 mg
* Drug: Amlodipine 5 mg
* Drug: Amlodipine 5 mg
* Drug: Amlodipine 2.5 mg
* Drug: Amlodipine 2.5 mg
* Drug: Amlodipine 10 mg
* Drug: Amlodipine 2.5 mg
* Drug: Telmisartan 80 mg
* Drug: Telmisartan 80 mg
* Drug: Amlodipine 5 mg
* Drug: Amlodipine 2.5 mg
* Drug: Telmisartan 40 mg
* Drug: Telmisartan 40 mg
* Drug: Amlodipine 5 mg
* Drug: Amlodipine 5 mg
* Drug: Telmisartan 40 mg
* Drug: Telmisartan 80 mg
* Drug: Amlodipine 10 mg


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Main Inclusion Criteria: Male and female patients >=18 years of age with Stage I or II hypertension defined as: a mean seated cuff diastolic blood pressure >=95 and <=119 mmHg Main Exclusion criteria: Exclusion Criteria: Patient is pregnant; breast-feeding; unwilling to use birth control during the study; has secondary hypertension; severe renal dysfunction; hepatic insufficiency; stroke within the last six months; myocardial infarction, cardiac surgery, percutaneous transluminal coronary angioplasty, unstable angina or coronary artery bypass graft within the past three months; unstable or uncontrolled diabetes for the past three months defined as a glucosylates hemoglobin (HbA1c) greater than ten percent ; history of angioedema or hypersensitivity related to either study drug. Systolic Blood Pressure (SBP) is greater than or equal to 180 millimeters of mercury (mmHg), Diastolic Blood Pressure (DBP) is greater than or equal to 110 mmHg.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
=================
How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo once daily for eight weeks | Drug: Placebo<br>* Placebo to Telmisartan and Amlodipine once daily for eight weeks<br>|
| Experimental: Telmisartan 20 mg<br>Telmisartan 20 mg once daily for eight weeks | Drug: Telmisartan 20 mg<br>* Telmisartan 20 mg once daily for eight weeks<br>|
| Experimental: Telmisartan 40 mg<br>Telmisartan 40 mg once daily for eight weeks | Drug: Telmisartan 40 mg<br>* Telmisartan 40 mg once daily for eight weeks<br>|
| Experimental: Telmisartan 80 mg<br>Telmisartan 80 mg once daily for eight weeks | Drug: Telmisartan 80 mg<br>* Telmisartan 80 mg once daily for eight weeks<br>|
| Experimental: Amlodipine 2.5 mg<br>Amlodipine 2.5 mg once daily for eight weeks | Drug: Amlodipine 2.5 mg<br>* Amlodipine 2.5 mg once daily for eight weeks<br>|
| Experimental: Amlodipine 5 mg<br>Amlodipine 5 mg once daily for eight weeks | Drug: Amlodipine 5 mg<br>* amlodipine 5g once daily for eight weeks<br>|
| Active Comparator: Amlodipine 10 mg<br>Amlodipine 5 mg for two weeks and forced titrated to amlodipine 10 mg for six weeks once daily | Drug: Amlodipine 5 mg<br>* amlodipine 5g once daily for two weeks<br>Drug: Amlodipine 10 mg<br>* Amlodipine 10 mg once daily for six weeks<br>|
| Experimental: Telmisartan 20 / Amlodipine 2.5<br>Telmisartan 20/ Amlodipine 2.5 mg once daily for eight weeks | Drug: Telmisartan 20 mg<br>* Telmisartan 20 mg once daily for eight weeks<br>Drug: Amlodipine 2.5 mg<br>* Amlodipine 2.5 mg once daily for eight weeks<br>|
| Experimental: Telmisartan 20 / Amlodipine 5<br>Telmisartan 20 / Amlodipine 5 mg once daily for eight weeks | Drug: Telmisartan 20 mg<br>* Telmisartan 20 mg once daily for eight weeks<br>Drug: Amlodipine 5 mg<br>* amlodipine 5mg once daily for eight weeks<br>|
| Experimental: Telmisartan 20 / Amlodipine 10<br>Telmisartan 20 / Amlodipine 5 for two weeks and forced titrated to amlodipine 10 mg for six weeks | Drug: Amlodipine 10 mg<br>* Amlodipine 10 mg once daily for six weeks<br>Drug: Telmisartan 20 mg<br>* Telmisartan 20 mg once daily for eight weeks<br>Drug: Amlodipine 5 mg<br>* Amlodipine 5 mg once daily for two weeks<br>|
| Experimental: Telmisartan 40 / Amlodipine 2.5<br>Telmisartan 40 / Amlodipine 2.5 for eight weeks | Drug: Amlodipine 2.5 mg<br>* Amlodipine 2.5 mg once daily for eight weeks<br>Drug: Telmisartan 40 mg<br>* Telmisartan 40 mg once daily for eight weeks<br>|
| Experimental: Telmisartan 40 / Amlodipine 5<br>Telmisartan 40 / Amlodipine 5 for eight weeks | Drug: Amlodipine 5 mg<br>* Amlodipine 5 mg once daily for eight weeks<br>Drug: Telmisartan 40 mg<br>* Telmisartan 40 mg once daily for eight weeks<br>|
| Experimental: Telmisartan 40 / Amlodipine 10<br>Telmisartan 40 / Amlodipine 5 for two weeks and forced titrated to amlodipine 10 mg for six weeks | Drug: Telmisartan 40 mg<br>* Telmisartan 40 mg once daily for eight weeks<br>Drug: Amlodipine 10 mg<br>* Amlodipine 10 mg once daily for six weeks<br>Drug: Amlodipine 5 mg<br>* Amlodipine 5 mg once daily for two weeks<br>|
| Experimental: Telmisartan 80 / Amlodipine 2.5<br>Telmisartan 80 / Amlodipine 2.5 for eight weeks | Drug: Amlodipine 2.5 mg<br>* Amlodipine 2.5 mg once daily for eight weeks<br>Drug: Telmisartan 80 mg<br>* Telmisartan 80 mg once daily for eight weeks<br>|
| Experimental: Telmisartan 80 / Amlodipine 5<br>Telmisartan 80 / Amlodipine 5 mg for eight weeks | Drug: Telmisartan 80 mg<br>* Telmisartan 80 mg once daily for eight weeks<br>Drug: Amlodipine 5 mg<br>* Amlodipine 5 mg once daily for eight weeks<br>|
| Experimental: Telmisartan 80 / Amlodipine 10<br>Telmisartan 40 / Amlodipine 5 for two weeks and forced titrated to amlodipine 10 mg for six weeks | Drug: Amlodipine 5 mg<br>* Amlodipine 5 mg once daily for two weeks<br>Drug: Telmisartan 80 mg<br>* Telmisartan 80 mg once daily for eight weeks<br>Drug: Amlodipine 10 mg<br>* Amlodipine 10 mg once daily for six weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline at 8 Weeks in Seated Trough Cuff Mean Diastolic Blood Pressure (DBP) (Observed Telmisartan Effect) | Observed results | Baseline to end-of-study (up to 8 weeks) visit (Last Observation Carried Forward (LOCF)) | 
| Change From Baseline at 8 Weeks in Seated Trough Cuff Mean DBP (Adjusted Telmisartan Effects) | Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate. | Baseline to end-of-study (up to 8 weeks) visit (LOCF) | 
| Change From Baseline at 8 Weeks in Seated Trough Cuff Mean DBP (Observed Amlodipine Effects) | Observed results | Baseline to end-of-study (up to 8 weeks) visit (LOCF) | 
| Change From Baseline at 8 Weeks in Seated Trough Cuff Mean DBP (Adjusted Amlodipine Effects) | Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate. | Baseline to end-of-study (up to 8 weeks) visit (LOCF) | 
| Change From Baseline at 8 Weeks in Seated Trough Cuff Mean DBP (Observed Treatment Effects) | Observed results | End-of-study visit (LOCF) | 
| Change From Baseline at 8 Weeks in Seated Trough Cuff Mean DBP (Adjusted Treatment Effects) | Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate. | Baseline to end-of-study (up to 8 weeks) visit (LOCF) | 
| Change From Baseline at 8 Weeks in Seated Trough Cuff Mean DBP (Adjusted Treatment Effects, Excluding Pl) | Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate. | Baseline to end-of-study (up to 8 weeks) visit (LOCF) | 
| Change From Baseline in Seated Trough Cuff Mean DBP (Observed Telmisartan Effect) | Observed results | Baseline to end-of-study (up to 8 weeks) visit (LOCF) | 
| Change From Baseline in Seated Trough Cuff Mean DBP (Adjusted Telmisartan Effects) | Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate. | Baseline to end-of-study (up to 8 weeks) visit (LOCF) | 
| Change From Baseline in Seated Trough Cuff Mean DBP (Observed Amlodipine Effects) | Observed results | Up to 8 weeks (LOCF) | 
| Change From Baseline in Seated Trough Cuff Mean DBP (Adjusted Amlodipine Effects) | Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate. | Up to 8 weeks (LOCF) | 
| Change From Baseline in Seated Trough Cuff Mean DBP (Observed Treatment Effects) | Observed results | Up to 8 weeks (LOCF) | 
| Change From Baseline in Seated Trough Cuff Mean DBP (Adjusted Treatment Effects) | Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate. | Up to 8 weeks (LOCF) | 
| Change From Baseline in Seated Trough Cuff Mean DBP (Adjusted Treatment Effects, Excluding Pl) | Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate. | Up to 8 weeks (LOCF) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline at 8 Weeks in Seated Trough Cuff Mean Systolic Blood Pressure (SBP) | Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline SBP included as a covariate. | Baseline to end-of-study (up to 8 weeks) visit (LOCF) | 
| Change From Baseline at 8 Weeks in Standing Trough Cuff Mean DBP | Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate. | Baseline to end-of-study (up to 8 weeks) visit (LOCF) | 
| Change From Baseline at 8 Weeks in Standing Trough Cuff Mean SBP | Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline SBP included as a covariate. | Baseline to end-of-study (up to 8 weeks) visit (LOCF) | 
| DBP Control | DBP control is defined as DBP < 90 mmHg - key combination therapies | End-of-study (up to 8 weeks) visit (LOCF) | 
| DBP Response | DBP response is defined as DBP < 90 mmHg or a reduction of DBP of >= 10 mmHg - key combination therapies | End-of-study (up to 8 weeks) visit (LOCF) | 
| SBP Response | SBP Response is defined as SBP < 140 mmHg or a reduction of SBP of >= 10 mmHg - key combination therapies | End-of-study (up to 8 weeks) visit (LOCF) | 
| BP Normality | No: Mean seated SBP >=140 and/or mean seated DBP >=90 mmHg at trough High normal: mean seated SBP >=130 and <140 mmHg and mean seated DBP >=85 and <90 mmHg at trough Normal: mean seated SBP >=120 and <130 mmHg and mean seated DBP >=80 and <85 mmHg at trough Optimal: mean seated SBP < 120 mmHg and mean seated DBP <80 mmHg at trough - key combination therapies | End-of-study (up to 8 weeks) visit (LOCF) | 
| Change From Baseline in ABPM Hourly Mean (Relative to Dosing) DBP | Observed results - key combination therapies | End-of-study (up to 8 weeks) visit (LOCF) | 
| Change From Baseline in ABPM Hourly Mean (Relative to Dosing) SBP | Observed results - key combination therapies | End-of-study (up to 8 weeks) visit (LOCF) | 
| Change From Baseline in ABPM 24-hour Mean DBP | Observed results - key combination therapies | End-of-study (up to 8 weeks) visit (LOCF) | 
| Change From Baseline in ABPM 24-hour Mean SBP | Observed results - key combination therapies | End-of-study (up to 8 weeks) visit (LOCF) | 
| Orthostatic Change in Trough Cuff Mean DBP | Calculated as seated minus standing for all patients - key combination therapies | Week 8 | 
| Orthostatic Change in Trough Cuff Mean SBP | Calculated as seated minus standing for all patients - key combination therapies | Week 8 | 
| Change From Baseline in Seated Trough Pulse Rate | Observed results for all patients - key combination therapies | End-of-study visit (LOCF) | 
| Change From Baseline in Seated Trough Cuff Mean SBP | Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline SBP included as a covariate. | Up to 8 weeks (LOCF) | 
| Change From Baseline in Standing Trough Cuff Mean DBP | Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline DBP included as a covariate. | Up to 8 weeks (LOCF) | 
| Change From Baseline in Standing Trough Cuff Mean SBP | Results stem from an ANCOVA including the main effects of treatment with telmisartan, treatment with amlodipine, and country/region with baseline SBP included as a covariate. | Up to 8 weeks (LOCF) | 
| DBP Control | DBP control is defined as DBP < 90 mmHg - key combination therapies | Up to 8 weeks (LOCF) | 
| DBP Response | DBP response is defined as DBP < 90 mmHg or a reduction of DBP of >= 10 mmHg - key combination therapies | Up to 8 weeks (LOCF) | 
| SBP Response | SBP Response is defined as SBP < 140 mmHg or a reduction of SBP of >= 10 mmHg - key combination therapies | Up to 8 weeks (LOCF) | 
| BP Normality | No: Mean seated SBP >=140 and/or mean seated DBP >=90 mmHg at trough High normal: mean seated SBP >=130 and <140 mmHg and mean seated DBP >=85 and <90 mmHg at trough Normal: mean seated SBP >=120 and <130 mmHg and mean seated DBP >=80 and <85 mmHg at trough Optimal: mean seated SBP < 120 mmHg and mean seated DBP <80 mmHg at trough - key combination therapies | Up to 8 weeks (LOCF) | 
| Change From Baseline in ABPM Hourly Mean (Relative to Dosing) DBP | Observed results for mod-sev patients - key combination therapies | Up to 8 weeks (LOCF) | 
| Change From Baseline in ABPM 24-hour Mean DBP | Observed results for mod-sev patients - key combination therapies | Up to 8 weeks (LOCF) | 
| Change From Baseline in ABPM 24-hour Mean SBP | Observed results for mod-sev patients - key combination therapies | Up to 8 weeks (LOCF) | 
| Orthostatic Change in Trough Cuff Mean DBP | Calculated as seated minus standing for mod-sev patients - key combination therapies | Week 8 | 
| Orthostatic Change in Trough Cuff Mean SBP | Calculated as seated minus standing for mod-sev patients - key combination therapies | Week 8 | 
| Change From Baseline in Seated Trough Pulse Rate | Observed results for mod-sev patients - key combination therapies | Up to 8 weeks (LOCF) | 
| Clinical Relevant Abnormalities for Laboratory Parameters and Electrocardiogram (ECG) | Clinical relevant abnormalities for laboratory parameters and Electrocardiogram (ECG). New abnormal findings or worsening of baseline conditions were reported as Adverse Events related to treatment (cardiac disorders and investigations). | 8 weeks |