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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension; Type 2 Diabetes
• Intervention / Treatment: Drug: Amlodipine; Drug: amlodipine / olmesartan medoxomil combination; Drug: Hydrochlorothiazide

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 207
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States
    • Sylmar, California, United States
    • Tustin, California, United States
  • Florida
    • Aventura, Florida, United States
    • DeLand, Florida, United States
    • Hialeah, Florida, United States
    • Pembroke Pines, Florida, United States
  • Indiana
    • Avon, Indiana, United States
    • Indianapolis, Indiana, United States
  • Nevada
    • Las Vegas, Nevada, United States
  • New York
    • New Windsor, New York, United States
  • North Carolina
    • Winston-Salem, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
  • South Carolina
    • Charleston, South Carolina, United States
    • Greer, South Carolina, United States
    • Taylors, South Carolina, United States
  • Tennessee
    • Nashville, Tennessee, United States
  • Texas
    • Dallas, Texas, United States
    • San Antonio, Texas, United States
  • Virginia
    • Burke, Virginia, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (Actual): April 1, 2009
• Study Completion (Actual): June 1, 2009

Study Registration Dates

• First Submitted: April 4, 2008
• First Submitted That Met QC Criteria: April 8, 2008
• First Posted (Estimate): April 9, 2008

Study Record Updates

• Last Update Posted (Estimate): July 13, 2010
• Last Update Submitted That Met QC Criteria: July 9, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Keywords: blood pressure reduction
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sodium Chloride Symporter Inhibitors; Amlodipine; Olmesartan; Olmesartan Medoxomil; Hydrochlorothiazide
• Other Study ID Numbers: CS-8663-403