A Dose Escalation Study of a Combination Antihypertensive Drug in the Treatment of Various Groups of Patients Who do Not Respond to Single Drug Treatment of Their High Blood Pressure

Study Overview
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Brief Summary
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The initial 12 week portion of this 20 week study will examine the ability of a combination of olmesartan medoxomil and amlodipine to lower the blood pressure of patients with high blood pressure who have not had sufficient blood pressure reduction using one anti-hypertension drug (monotherapy). The final 8 weeks of this 20 week study will examine the ability of a combination of olmesartan medoxomil, amlodipine and hydrochlorothiazide to lower blood pressure in the same patient population. All three medications being tested have been approved by the FDA for the treatment of high blood pressure, but only amlodipine and olmesartan are currently approved for use in combination form.

Official Title
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A Prospective, Open-Label, Titration Study to Evaluate the Efficacy and Safety Safety of AZOR in Multiple Subgroups of Hypertensive Subjects Who Are Non-Responders to Anti-Hypertensive Monotherapy

Conditions
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Hypertension

Intervention / Treatment
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* Drug: amlodipine and olmesartan medoxomil tablets
* Drug: hydrochlorothiazide tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >= to 18 years of age Hypertension uncontrolled on current monotherapy Females: negative serum pregnancy test at screening post menopausal or have had a hysterectomy or tubal ligation or practicing approved methods of birth control Exclusion Criteria: Pregnant females Uncontrolled hypertension with multiple drugs, except for hydrochlorothiazide/triamterene Diabetes requiring insulin Serious disorders that may limit the ability to evaluate the efficacy or safety of treatment History of myocardial infarction, bypass graft, angioplasty or heart failure within the past 6 months History of Class III or IV congestive heart failure History of stroke or transient ischemic attack within the last 1 year

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
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Azor tablets and hydrochlorothiazide tablets (if necessary) will be administered for up to 20 weeks | Drug: amlodipine and olmesartan medoxomil tablets<br>* amlodipine and olmesartan medoxomil tablets administered orally, once daily for up to 20 weeks<br>* Other names: AZOR Tablets;Drug: hydrochlorothiazide tablets<br>* hydrochlorothiazide tablets may be administered orally, if necessary once daily, for up to 8 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Patients Who Achieve Seated Systolic Blood Pressure Goal (<140 mm Hg for Non-diabetics and <130 mm Hg for Diabetics) From Baseline to 12 Weeks |  | baseline to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Subjects Achieving Seated Diastolic BP Goal (<90 mmHg for Non-diabetics or < 80 mmHg for Subjects With Diabetes) From Baseline to 12 Weeks |  | baseline to 12 weeks | 
| The Percentage of Subjects Who Achieve BP Goal (<140/90 mmHg for Non-diabetics or <130/80 mmHg for Diabetics) From Baseline to 12 and 20 Weeks |  | Baseline to 12 and 20 weeks | 
| Change in Mean Seated Systolic Blood Pressure From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Change in Mean Seated Diastolic Blood Pressure From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Patients Achieving Seated Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Participants Achieving the Mean Daytime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 12 Weeks | Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours. Daytime is defined as 8AM - 4PM. | Baseline to 12 weeks | 
| Percentage of Participants Achieving the Mean Daytime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 20 Weeks | Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours. Daytime is defined as 8AM - 4PM. | Baseline to 20 weeks | 
| Percentage of Participants Achieving the Mean Nighttime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 12 Weeks | Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours. Nighttime is defined as 10p.m. - 6 a.m. | Baseline to 12 weeks | 
| Percentage of Participants Achieving the Mean Nighttime Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 20 Weeks | Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours. Nighttime is defined as 10 p.m. - 6 a.m. | Baseline to 20 weeks | 
| Percentage of Participants Achieving the Mean 24-hour Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 12 Weeks | Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours. | Baseline to 12 weeks | 
| Percentage of Participants Achieving the Mean 24-hour Blood Pressure Goals, as Measured by Ambulatory Blood Pressure Monitor, From Baseline to 20 Weeks | Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours. | Baseline to 20 weeks | 
| Change From Baseline to Week 12 in Ambulatory Systolic and Diastolic Blood Pressure Values | Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours. Daytime is defined as 8 a.m. to 4 p.m. Nighttime is defined as 10 p.m. to 6 a.m. | Baseline to 12 weeks | 
| Change From Baseline to Week 20 in Ambulatory Systolic and Diastolic Blood Pressure Values | Once the Ambulatory Blood Pressure Monitor (ABPM) has been applied, the dose of medication was taken and the subject wore the ABPM for a period of 24 hours. Daytime is defined as 8 a.m. to 4 p.m. Nighttime is defined as 10 p.m. to 6 a.m. | Baseline to 20 weeks | 
| Percentage of African American/Black Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of African American/Black Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of African American/Black Patients Achieving Seated Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of African American/Black Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of African American/Black Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Asian Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Asain Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Asian Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Asian Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Hispanic Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Hispanic Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Hispanic Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Hispanic Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Elderly Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Elderly Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Elderly Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Elderly Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Type 2 Diabetic Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Type 2 Diabetic Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Type 2 Diabetic Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Type 2 Diabetic Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Obese Patients Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Obese Patients Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Obese Patients Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Obese Patients Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Patients With Metabolic Syndrome Achieving Seated Systolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Patients With Metabolic Syndrome Achieving Seated Diastolic Blood Pressure Goal From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Patients With Metabolic Syndrome Achieving Seated Systolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Patients With Metabolic Syndrome Achieving Seated Diastolic Blood Pressure Reduction Ranges From Baseline to 4, 8, 12, 16, 20 Weeks |  | Baseline to 4, 8, 12, 16, 20 weeks | 
| Percentage of Participants Previously on a Dihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks |  | Baseline to 12 weeks | 
| Percentage of Participants Previously on a Dihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks |  | Baseline to 20 weeks | 
| Percentage of Participants Previously on a Diuretic Achieving the Blood Pressure Goals From Baseline to 12 Weeks |  | Baseline to 12 weeks | 
| Percentage of Participants Previously on a Diuretic Achieving the Blood Pressure Goals From Baseline to 20 Weeks |  | Baseline to 20 weeks | 
| Percentage of Participants Previously on an Angiotensin Converting Enzyme Inhibitor Achieving the Blood Pressure Goals From Baseline to 12 Weeks |  | Baseline to 12 weeks | 
| Percentage of Participants Previously on an Angiotensin Converting Enzyme Inhibitor Achieving the Blood Pressure Goals From Baseline to 20 Weeks |  | Baseline to 20 weeks | 
| Percentage of Participants Previously on an Angiotensin II Receptor Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks |  | Baseline to 12 weeks | 
| Percentage of Participants Previously on an Angiotensin II Receptor Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks |  | Baseline to 20 weeks | 
| Percentage of Participants Previously on a Beta Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks |  | Baseline to 12 weeks | 
| Percentage of Participants Previously on a Beta Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks |  | Baseline to 20 weeks | 
| Percentage of Participants Previously on a Nondihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 12 Weeks |  | Baseline to 12 weeks | 
| Percentage of Participants Previously on a Nondihydropyridine Calcium Channel Blocker Achieving the Blood Pressure Goals From Baseline to 20 Weeks |  | Baseline to 20 weeks |