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

Phase 4

Completed

Conditions: Type 2 Diabetes
Hypertension

Interventions: Drug: Amlodipine
Drug: amlodipine / olmesartan medoxomil combination
Drug: Hydrochlorothiazide

Registration Number: NCT00654745

Lead Sponsor: Daiichi Sankyo

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 207

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
aml + olm + hctz	amlodipine / olmesartan medoxomil combination	amlodipine; and olmesartan medoxomil, if required; and hydrochlorothiazide, if required.
aml + olm + hctz	Amlodipine	amlodipine; and olmesartan medoxomil, if required; and hydrochlorothiazide, if required.
aml + olm + hctz	Hydrochlorothiazide	amlodipine; and olmesartan medoxomil, if required; and hydrochlorothiazide, if required.

Primary Outcome Measures

Name	Time	Method
Change From Week 0 (Baseline) in Mean 24-hour Ambulatory Blood Pressure Monitoring (ABPM) Systolic Blood Pressure (SBP) After 12 Weeks of Active Treatment	week 0 - week 12	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.

Secondary Outcome Measures

Name	Time	Method
Change From Week 0 (Baseline) in Mean ABPM Diastolic Blood Pressure (DBP) After 12 Weeks of Active Treatment	week 0 - week 12 (24-hour, Daytime, Nighttime, Last 6 hour, Last 4 hour, Last 2 hour)	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
Change From Week 0 (Baseline) in Mean ABPM SBP After 12 Weeks of Active Treatment	week 0 - week 12 (24-hour, Daytime, Nighttime, Last 6 hour, Last 4 hour, Last 2 hour)	Daytime mean SBP, Nighttime mean SBP, Last 6 hour mean SBP, Last 4 hour mean SBP, Last 2 hour mean SBP
Change in Mean Seated Systolic Blood Pressure (SeSBP) From Week 0 (Baseline) After 3, 6, 9, 12, 15, and 18 Weeks	week 0 - weeks 3, 6, 9, 12, 15, 18	change in mean SeSBP from week 0 (baseline) to Weeks 3, 6, 9, 12, 15, and 18.
Change in Mean Seated Diastolic Blood Pressure (SeDBP) From Week 0 (Baseline) After 3, 6, 9, 12, 15, and 18 Weeks	week 0 - weeks 3, 6, 9, 12, 15, 18	change in mean SeDBP from week 0 (baseline) to Weeks 3, 6, 9, 12, 15, and 18.
Number of Participants Achieving Mean 24-hour Ambulatory Blood Pressure Thresholds at Week 12	week 0 - 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
Number of Participants Achieving Mean Daytime Ambulatory Blood Pressure Thresholds at Week 12	week 0 - 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
Number of Participants Achieving Mean Nighttime Ambulatory Blood Pressure Thresholds at Week 12	week 0 - 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
Number of Participants Achieving Mean Last 6 Hour Ambulatory Blood Pressure Thresholds at Week 12	week 0 - 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
Number of Participants Achieving Mean Last 4 Hour Ambulatory Blood Pressure Thresholds at Week 12	week 0 - 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
Number of Participants Achieving Mean Last 2 Hour Ambulatory Blood Pressure Thresholds at Week 12	week 0 - 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
Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 3	week 0 - 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
Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 6	week 0 - 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
Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 9	week 0 - 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
Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 12	week 0 - 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
Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 15	week 0 - 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
Number of Participants Achieving Seated Systolic and Diastolic Blood Pressure Thresholds at Week 18	week 0 - 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
Number of Participants Achieving Mean 24 Hour Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12	week 0 - 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
Number of Participants Achieving Mean Daytime Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12	week 0 - 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
Number of Participants Achieving Mean Nighttime Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12	week 0 - 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
Number of Participants Achieving Mean Last 6 Hour Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12	week 0 - 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
Number of Participants Achieving Mean Last 4 Hour Ambulatory Systolic and Diastolic Blood Pressure Reductions	week 0 - week 12	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
Number of Participants Achieving Mean Last 2 Hour Ambulatory Systolic and Diastolic Blood Pressure Reductions at Week 12	week 0 - 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
Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 3	week 0 - 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
Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 6	week 0 - 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
Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 9	week 0 - 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
Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 12	week 0 - 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
Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 15	week 0 - 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
Number of Participants Achieving Mean Seated Systolic and Diastolic Blood Pressure Reductions at Week 18	week 0 - 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