18 Week Study Evaluating Safety and Efficacy of Olmesartan, Amlodipine, and Hydrochlorothiazide, in Type 2 Diabetics

Study Overview
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Brief Summary
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To determine if olmesartan plus amlodipine combination therapy alone and with hydrochlorothiazide will be safe and effective to reduce high blood pressure in hypertensive, type 2 diabetic subjects.

Detailed Description
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This is a single group study in which participants were titrated to the next of 6 regimens if blood pressure (BP) goals were not met.

Official Title
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A Prospective, Open-label, Ambulatory Blood Pressure Monitoring (ABPM) Dose Titration Study to Evaluate the Safety and Efficacy of an Olmesartan Medoxomil and Amlodipine Based Treatment Regimen in Hypertensive, Type 2 Diabetic Subjects

Conditions
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Type 2 Diabetes, Hypertension

Intervention / Treatment
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* Drug: Amlodipine
* Drug: amlodipine / olmesartan medoxomil combination
* Drug: Hydrochlorothiazide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged 18 to 80 years. Diagnosis of type 2 diabetes mellitus and on a stable regimen of any oral antidiabetic agent(s) for at least 3 months, with or without adjunctive use of Byetta (exenatide); Note: Subjects diagnosed with type 2 diabetes mellitus who were not on oral antidiabetic agents may have been enrolled if they had a documented history of type 2 diabetes by American Diabetes Association criteria, including the specific plasma glucose results listed below: Fasting plasma glucose >=126 mg/dL (7.0 mmol/L); or Symptoms of hyperglycemia and a casual (any time of day without regard to time since last meal) plasma glucose >=200 mg/dL (11.1 mmol/L). The classic symptoms of hyperglycemia were considered to include polyuria, polydipsia, and unexplained weight loss; or Two-hour plasma glucose >=200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test; Newly diagnosed hypertension or uncontrolled hypertension (defined as SBP >130 mmHg and/or DBP >80 mmHg) on current antihypertensive monotherapy or combination therapy. Subjects must fulfill mean seated office blood pressure parameters at two consecutive, qualifying visits during the placebo run-in phase, and, subsequently, daytime ambulatory blood pressure monitoring (ABPM) criteria. Females should not be pregnant or lactating and, if applicable, using adequate contraception. Exclusion Criteria: Subjects with uncontrolled hypertension taking multiple antihypertensive therapies (at the discretion of the investigator). Type 2 diabetes mellitus with a glycosylated hemoglobin A1c (HbA1c) >=9.0% at screening; Subjects with type 1 or type 2 diabetes mellitus requiring insulin. Subjects with any serious disorder which may limit the ability to evaluate the safety and efficacy of study medication, or subjects with secondary hypertension.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: aml + olm + hctz<br>amlodipine; and olmesartan medoxomil, if required; and hydrochlorothiazide, if required. | Drug: Amlodipine<br>* Amlodipine 5 mg tablets , Daily for 3 weeks;<br>* Other names: Norvasc;Drug: amlodipine / olmesartan medoxomil combination<br>* amlodipine / olmesartan medoxomil combination tablets 5 mg/20 mg or 5 mg/40 mg or 10 mg/40 mg<br>* Other names: Azor;Drug: Hydrochlorothiazide<br>* hydrochlorothiazide tablets, 12.5 mg or 25 mg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Week 0 (Baseline) in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (SBP) After 12 Weeks of Active Treatment | Change from week 0 (baseline) in mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (SBP) after 12 weeks of active treatment. change = week 12 - week 0. | week 0 - week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Week 0 (Baseline) in Mean ABPM Diastolic Blood Pressure (DBP) After 12 Weeks of Active Treatment | 24-hour mean DBP, Daytime mean DBP, Nighttime mean DBP, Last 6 hour mean DBP, Last 4 hour mean DBP, Last 2 hour mean DBP | week 0 - week 12 (24-hour, Daytime, Nighttime, Last 6 hour, Last 4 hour, Last 2 hour) | 
| Change From Week 0 (Baseline) in Mean ABPM SBP After 12 Weeks of Active Treatment | Daytime mean SBP, Nighttime mean SBP, Last 6 hour mean SBP, Last 4 hour mean SBP, Last 2 hour mean SBP | week 0 - week 12 (24-hour, Daytime, Nighttime, Last 6 hour, Last 4 hour, Last 2 hour) | 
| Change in Mean Seated Systolic Blood Pressure (SeSBP) From Week 0 (Baseline) After 3, 6, 9, 12, 15, and 18 Weeks | change in mean SeSBP from week 0 (baseline) to Weeks 3, 6, 9, 12, 15, and 18. | week 0 - weeks 3, 6, 9, 12, 15, 18 | 
| Change in Mean Seated Diastolic Blood Pressure (SeDBP) From Week 0 (Baseline) After 3, 6, 9, 12, 15, and 18 Weeks | change in mean SeDBP from week 0 (baseline) to Weeks 3, 6, 9, 12, 15, and 18. | week 0 - weeks 3, 6, 9, 12, 15, 18 | 
| Number of Participants Achieving Mean 24-hour Ambulatory Blood Pressure Thresholds at Week 12 | number of participants achieving mean 24-hour ambulatory blood pressure thresholds BP<135/85, BP<130/80, BP<125/75, BP<120/80, SBP<135, SBP<130, SBP<125, SBP<120, DBP<85, DBP<80, DBP<75 at week 12 | week 0 - week 12 | 
| Number of Participants Achieving Mean Daytime Ambulatory Blood Pressure Thresholds at Week 12 | number of participants achieving mean daytime ambulatory blood pressure thresholds BP<135/85, BP<130/80, BP<125/75, BP<120/80, SBP<135, SBP<130, SBP<125, SBP<120, DBP<85, DBP<80, DBP<75 at week 12 | week 0 - week 12 | 
| Number of Participants Achieving Mean Nighttime Ambulatory Blood Pressure Thresholds at Week 12 | number of participants achieving mean nighttime ambulatory blood pressure thresholds BP<135/85, BP<130/80, BP<125/75, BP<120/80, BP<120/70, SBP<135, SBP<130, SBP<125, SBP<120, DBP<85, DBP<80, DBP<75, DBP<70 at week 12 | week 0 - week 12 | 
| Number of Participants Achieving Mean Last 6 Hour Ambulatory Blood Pressure Thresholds at Week 12 | number participants achieving mean last 6 hour ambulatory blood pressure thresholds BP<135/85, BP<130/80, BP<125/75, BP<120/80, SBP<135, SBP<130, SBP<125, SBP<120, DBP<85, DBP<80, DBP<75 at week 12 | week 0 - week 12 | 
| Number of Participants Achieving Mean Last 4 Hour Ambulatory Blood Pressure Thresholds at Week 12 | number of participants achieving mean last 4 hour ambulatory blood pressure thresholds BP<135/85, BP<130/80, BP<125/75, BP<120/80, SBP<135, SBP<130, SBP<125, SBP<120, DBP<85, DBP<80, DBP<75 at week 12 | week 0 - week 12 | 
| Number of Participants Achieving Mean Last 2 Hour Ambulatory Blood Pressure Thresholds at Week 12 | number of participants achieving mean last 2 hour ambulatory blood pressure thresholds BP<135/85, BP<130/80, BP<125/75, BP<120/80, SBP<135, SBP<130, SBP<125, SBP<120, DBP<85, DBP<80, DBP<75 at week 12 | week 0 - week 12 | 
| Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 3 | number of participants achieving seated systolic and diastolic blood pressure thresholds BP<135/85, BP<130/80, BP<125/75, BP<120/80, SBP<135, SBP<130, SBP<125, SBP<120, DBP<85, DBP<80, DBP<75 at week 3 | week 0 - week 3 | 
| Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 6 | number of participants achieving seated systolic and diastolic blood pressure thresholds BP<135/85, BP<130/80, BP<125/75, BP<120/80, SBP<135, SBP<130, SBP<125, SBP<120, DBP<85, DBP<80, DBP<75 at week 6 | week 0 - week 6 | 
| Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 9 | number of participants achieving seated systolic and diastolic blood pressure thresholds BP<135/85, BP<130/80, BP<125/75, BP<120/80, SBP<135, SBP<130, SBP<125, SBP<120, DBP<85, DBP<80, DBP<75 at week 9 | week 0 - week 9 | 
| Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 12 | number of participants achieving seated systolic and diastolic blood pressure thresholds BP<135/85, BP<130/80, BP<125/75, BP<120/80, SBP<135, SBP<130, SBP<125, SBP<120, DBP<85, DBP<80, DBP<75 at week 12 | week 0 - week 12 | 
| Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 15 | number of participants achieving seated systolic and diastolic blood pressure thresholds BP<135/85, BP<130/80, BP<125/75, BP<120/80, SBP<135, SBP<130, SBP<125, SBP<120, DBP<85, DBP<80, DBP<75 at week 15 | week 0 - week 15 | 
| Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 18 | number of participants achieving seated systolic and diastolic blood pressure thresholds BP<135/85, BP<130/80, BP<125/75, BP<120/80, SBP<135, SBP<130, SBP<125, SBP<120, DBP<85, DBP<80, DBP<75 at week 18 | week 0 - week 18 | 
| Number of Participants Achieving Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12 | number of participants achieving mean 24 hour ambulatory systolic and diastolic blood pressure reductions of; SBP reduction <= 15 mmHg, SBP reduction > 15 mmHg & <= 30 mmHg, SBP reduction > 30 mmHg & <= 45 mmHg, SBP reduction > 45 mmHg, DBP reduction <= 10 mmHg, DBP reduction > 10 mmHg & <= 15 mmHg, DBP reduction > 15 mmHg & <= 20 mmHg, DBP reduction > 20 mmHg at week 12 | week 0 - week 12 | 
| Number of Participants Achieving Mean Daytime Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12 | number of participants achieving mean daytime ambulatory systolic and diastolic blood pressure reductions of; SBP reduction <= 15 mmHg, SBP reduction > 15 mmHg & <= 30 mmHg, SBP reduction > 30 mmHg & <= 45 mmHg, SBP reduction > 45 mmHg, DBP reduction <= 10 mmHg, DBP reduction > 10 mmHg & <= 15 mmHg, DBP reduction > 15 mmHg & <= 20 mmHg, DBP reduction > 20 mmHg at week 12 | week 0 - week 12 | 
| Number of Participants Achieving Mean Nighttime Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12 | number of participants achieving mean nighttime ambulatory systolic and diastolic blood pressure reductions of; SBP reduction <= 15 mmHg, SBP reduction > 15 mmHg & <= 30 mmHg, SBP reduction > 30 mmHg & <= 45 mmHg, SBP reduction > 45 mmHg, DBP reduction <= 10 mmHg, DBP reduction > 10 mmHg & <= 15 mmHg, DBP reduction > 15 mmHg & <= 20 mmHg, DBP reduction > 20 mmHg at week 12 | week 0 - week 12 | 
| Number of Participants Achieving Mean Last 6 Hour Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12 | number of participants achieving mean last 6 hour ambulatory systolic and diastolic blood pressure reductions of; SBP reduction <= 15 mmHg, SBP reduction > 15 mmHg & <= 30 mmHg, SBP reduction > 30 mmHg & <= 45 mmHg, SBP reduction > 45 mmHg, DBP reduction <= 10 mmHg, DBP reduction > 10 mmHg & <= 15 mmHg, DBP reduction > 15 mmHg & <= 20 mmHg, DBP reduction > 20 mmHg at week 12 | week 0 - week 12 | 
| Number of Participants Achieving Mean Last 4 Hour Ambulatory Systolic and Diastolic Blood Pressure Reductions | number of participants achieving mean last 4 hour ambulatory systolic and diastolic blood pressure reductions of; SBP reduction <= 15 mmHg, SBP reduction > 15 mmHg & <= 30 mmHg, SBP reduction > 30 mmHg & <= 45 mmHg, SBP reduction > 45 mmHg, DBP reduction <= 10 mmHg, DBP reduction > 10 mmHg & <= 15 mmHg, DBP reduction > 15 mmHg & <= 20 mmHg, DBP reduction > 20 mmHg at week 12 | week 0 - week 12 | 
| Number of Participants Achieving Mean Last 2 Hour Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12 | number of participants achieving mean last 2 hour ambulatory systolic and diastolic blood pressure reductions of; SBP reduction <= 15 mmHg, SBP reduction > 15 mmHg & <= 30 mmHg, SBP reduction > 30 mmHg & <= 45 mmHg, SBP reduction > 45 mmHg, DBP reduction <= 10 mmHg, DBP reduction > 10 mmHg & <= 15 mmHg, DBP reduction > 15 mmHg & <= 20 mmHg, DBP reduction > 20 mmHg at week 12 | week 0 - week 12 | 
| Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 3 | number of participants achieving mean seated systolic and diastolic blood pressure reductions of; SBP reduction <= 15 mmHg, SBP reduction > 15 mmHg & <= 30 mmHg, SBP reduction > 30 mmHg & <= 45 mmHg, SBP reduction > 45 mmHg, DBP reduction <= 10 mmHg, DBP reduction > 10 mmHg & <= 15 mmHg, DBP reduction > 15 mmHg & <= 20 mmHg, DBP reduction > 20 mmHg at week 3 | week 0 - week 3 | 
| Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 6 | number of participants achieving mean seated systolic and diastolic blood pressure reductions of; SBP reduction <= 15 mmHg, SBP reduction > 15 mmHg & <= 30 mmHg, SBP reduction > 30 mmHg & <= 45 mmHg, SBP reduction > 45 mmHg, DBP reduction <= 10 mmHg, DBP reduction > 10 mmHg & <= 15 mmHg, DBP reduction > 15 mmHg & <= 20 mmHg, DBP reduction > 20 mmHg at week 6 | week 0 - week 6 | 
| Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 9 | number of participants achieving mean seated systolic and diastolic blood pressure reductions of; SBP reduction <= 15 mmHg, SBP reduction > 15 mmHg & <= 30 mmHg, SBP reduction > 30 mmHg & <= 45 mmHg, SBP reduction > 45 mmHg, DBP reduction <= 10 mmHg, DBP reduction > 10 mmHg & <= 15 mmHg, DBP reduction > 15 mmHg & <= 20 mmHg, DBP reduction > 20 mmHg at week 9 | week 0 - week 9 | 
| Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 12 | number of participants achieving mean seated systolic and diastolic blood pressure reductions of; SBP reduction <= 15 mmHg, SBP reduction > 15 mmHg & <= 30 mmHg, SBP reduction > 30 mmHg & <= 45 mmHg, SBP reduction > 45 mmHg, DBP reduction <= 10 mmHg, DBP reduction > 10 mmHg & <= 15 mmHg, DBP reduction > 15 mmHg & <= 20 mmHg, DBP reduction > 20 mmHg at week 12 | week 0 - week 12 | 
| Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 15 | number of participants achieving mean seated systolic and diastolic blood pressure reductions of; SBP reduction <= 15 mmHg, SBP reduction > 15 mmHg & <= 30 mmHg, SBP reduction > 30 mmHg & <= 45 mmHg, SBP reduction > 45 mmHg, DBP reduction <= 10 mmHg, DBP reduction > 10 mmHg & <= 15 mmHg, DBP reduction > 15 mmHg & <= 20 mmHg, DBP reduction > 20 mmHg at week 15 | week 0 - week 15 | 
| Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 18 | number of participants achieving mean seated systolic and diastolic blood pressure reductions of; SBP reduction <= 15 mmHg, SBP reduction > 15 mmHg & <= 30 mmHg, SBP reduction > 30 mmHg & <= 45 mmHg, SBP reduction > 45 mmHg, DBP reduction <= 10 mmHg, DBP reduction > 10 mmHg & <= 15 mmHg, DBP reduction > 15 mmHg & <= 20 mmHg, DBP reduction > 20 mmHg at week 18 | week 0 - week 18 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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blood pressure reduction