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

Official Title: “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”

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.

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.

Intervention(s) in this Clinical Trial

• Drug: Amlodipine
  • Amlodipine 5 mg tablets , Daily for 3 weeks;
• Drug: amlodipine / olmesartan medoxomil combination
  • amlodipine / olmesartan medoxomil combination tablets 5 mg/20 mg or 5 mg/40 mg or 10 mg/40 mg
• Drug: Hydrochlorothiazide
  • hydrochlorothiazide tablets, 12.5 mg or 25 mg.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: aml + olm + hctz
  • amlodipine; and olmesartan medoxomil, if required; and hydrochlorothiazide, if required.

Primary Measures

• Change From Week 0 (Baseline) in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (SBP) After 12 Weeks of Active Treatment
  • Time Frame: week 0 - week 12
    Safety Issue?: No

Secondary Measures

• Change From Week 0 (Baseline) in Mean ABPM Diastolic Blood Pressure (DBP) After 12 Weeks of Active Treatment
  • Time Frame: week 0 - week 12 (24-hour, Daytime, Nighttime, Last 6 hour, Last 4 hour, Last 2 hour)
    Safety Issue?: No
• Change From Week 0 (Baseline) in Mean ABPM SBP After 12 Weeks of Active Treatment
  • Time Frame: week 0 - week 12 (24-hour, Daytime, Nighttime, Last 6 hour, Last 4 hour, Last 2 hour)
    Safety Issue?: No
• Change in Mean Seated Systolic Blood Pressure (SeSBP) From Week 0 (Baseline) After 3, 6, 9, 12, 15, and 18 Weeks
  • Time Frame: week 0 - weeks 3, 6, 9, 12, 15, 18
    Safety Issue?: No
• Change in Mean Seated Diastolic Blood Pressure (SeDBP) From Week 0 (Baseline) After 3, 6, 9, 12, 15, and 18 Weeks
  • Time Frame: week 0 - weeks 3, 6, 9, 12, 15, 18
    Safety Issue?: No
• Number of Participants Achieving Mean 24-hour Ambulatory Blood Pressure Thresholds at Week 12
  • Time Frame: week 0 - week 12
    Safety Issue?: No
• Number of Participants Achieving Mean Daytime Ambulatory Blood Pressure Thresholds at Week 12
  • Time Frame: week 0 - week 12
    Safety Issue?: No
• Number of Participants Achieving Mean Nighttime Ambulatory Blood Pressure Thresholds at Week 12
  • Time Frame: week 0 - week 12
    Safety Issue?: No
• Number of Participants Achieving Mean Last 6 Hour Ambulatory Blood Pressure Thresholds at Week 12
  • Time Frame: week 0 - week 12
    Safety Issue?: No
• Number of Participants Achieving Mean Last 4 Hour Ambulatory Blood Pressure Thresholds at Week 12
  • Time Frame: week 0 - week 12
    Safety Issue?: No
• Number of Participants Achieving Mean Last 2 Hour Ambulatory Blood Pressure Thresholds at Week 12
  • Time Frame: week 0 - week 12
    Safety Issue?: No
• Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 3
  • Time Frame: week 0 - week 3
    Safety Issue?: No
• Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 6
  • Time Frame: week 0 - week 6
    Safety Issue?: No
• Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 9
  • Time Frame: week 0 - week 9
    Safety Issue?: No
• Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 12
  • Time Frame: week 0 - week 12
    Safety Issue?: No
• Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 15
  • Time Frame: week 0 - week 15
    Safety Issue?: No
• Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 18
  • Time Frame: week 0 - week 18
    Safety Issue?: No
• Number of Participants Achieving Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12
  • Time Frame: week 0 - week 12
    Safety Issue?: No
• Number of Participants Achieving Mean Daytime Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12
  • Time Frame: week 0 - week 12
    Safety Issue?: No
• Number of Participants Achieving Mean Nighttime Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12
  • Time Frame: week 0 - week 12
    Safety Issue?: No
• Number of Participants Achieving Mean Last 6 Hour Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12
  • Time Frame: week 0 - week 12
    Safety Issue?: No
• Number of Participants Achieving Mean Last 4 Hour Ambulatory Systolic and Diastolic Blood Pressure Reductions
  • Time Frame: week 0 - week 12
    Safety Issue?: No
• Number of Participants Achieving Mean Last 2 Hour Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12
  • Time Frame: week 0 - week 12
    Safety Issue?: No
• Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 3
  • Time Frame: week 0 - week 3
    Safety Issue?: No
• Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 6
  • Time Frame: week 0 - week 6
    Safety Issue?: No
• Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 9
  • Time Frame: week 0 - week 9
    Safety Issue?: No
• Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 12
  • Time Frame: week 0 - week 12
    Safety Issue?: No
• Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 15
  • Time Frame: week 0 - week 15
    Safety Issue?: No
• Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 18
  • Time Frame: week 0 - week 18
    Safety Issue?: No

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 80 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Daiichi Sankyo Inc. Industry

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00654745

Study ID Number: CS-8663-403

ClinicalTrials.gov Identifier: NCT00654745

Health Authority: United States: Food and Drug Administration