Hypertension
Conditions
Keywords
Hypertension, Angiotensin Receptor Blocker, Calcium Channel Blocker, Angiotensin Converting Enzyme Inhibitor, Hydrochlorothiazide, Stage I and II Hypertension, Type II Diabetes
Brief summary
This study will examine the ability of olmesartan medoxomil to lower the blood pressure of patients with Type II diabetes and high blood pressure. The medication being tested has been approved by the FDA for the treatment of high blood pressure.
Interventions
DRUGolmesartan medoxomil
Olmesartan medoxomil tablets, once daily
DRUGOlmesartan medoxomil plus Hydrochlorothiazide
Olmesartan medoxomil and hydrochlorothiazide combination tablets, once daily, if necessary
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients diagnosed with Type II diabetes that are on stable treatment with hypoglycemic agents * Patients with a mean seated systolic blood pressure (MSSBP) greater than or equal to 140 mmHg but \<200 mmHg and a MSDBP less than or equal to 114 mmHg following a 3 to 4-week single-blind placebo run-in period * The difference in MSSBP between Visits 3 and 4 or between Visits 4 and 4X must be less than or equal to 10 mmHg * Patients with a mean daytime (8AM - 4PM) SBP \> 130 mmHg and less than or equal to 199 mmHg and a mean daytime DBP less than or equal to 114 as measured by an ambulatory blood pressure monitoring device (ABPM) following placebo run-in period * If female, must have negative serum pregnancy test at screening and be either post-menopausal, had a hysterectomy or tubal ligation at least 6 months before consent or if of childbearing potential, must practice approved measures of birth control throughout study
Exclusion criteria
* History of stroke or transient ischemic attack (TIA) within the last one year * History of myocardial infarction, percutaneous transluminal coronary revascularization, coronary artery bypass graft, and/or unstable angina pectoris within the past 6 months * Presence of overt proteinuria at screening * Severe hypertension (DBP greater than or equal to 115 mmHg or SBP greater than or equal to 200 mmHg) * Patients with secondary hypertension of any etiology, such as renal disease, pheochromocytoma, or Cushing's syndrome * Type I or Type II diabetes requiring insulin * Evidence of symptomatic resting bradycardia, congestive heart failure, or hemodynamically significant cardiac valvular disease * Presence of heart block greater than first degree sinoatrial block, Wolff-Parkinson-White Syndrome, Sick Sinus Syndrome, Atrial fibrillation, or Atrial Flutter
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in Systolic BP (SBP) as Measured by 24-hour ABPM. | baseline and 12 weeks | Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 12 in Ambulatory BP Measurement (Systolic)During the Last 2 Hours of the Last (Week 12) 24-hour Dosing Period. | baseline and 12 weeks | Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study. |
| Change From Baseline to Week 12 in Ambulatory BP Measurement (Systolic)During the Last 4 Hours of the Last (Week 12 ) 24-hour Dosing Period. | baseline and 12 weeks | Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study. |
| Change From Baseline to Week 12 in Ambulatory BP Measurement (Systolic)During the Last 6 Hours of the Last (Week 12 ) 24-hour Dosing Period. | baseline and 12 weeks | Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study. |
| Change From Baseline to Week 12 in Mean Daytime and Nighttime Ambulatory Blood Pressure Measurement (Systolic). | baseline and 12 weeks | Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study. |
| Change in Daytime and Nighttime Ambulatory Blood Pressure (Diastolic) From Baseline to Week 12 | baseline and 12 weeks | Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study. |
| Change in Ambulatory Blood Pressure (Diastolic) From Baseline to Week 12 During the Last 2 Hours of the Last (Week 12 ) 24-hour Dosing Period. | baseline and 12 Weeks | Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study. |
| Change in Ambulatory BP (Diastolic) From Baseline to Week 12 During the Last (Week 12 ) 4 and 6 Hours of the Last 24-hour Dosing Period. | baseline and 12 weeks | Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study. |
| Change From Baseline to Week 12 in Mean 24-hour Ambulatory BP (Diastolic) | baseline and 12 weeks | Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited at 24 US sites over 10 months from November 2006 to August 2007 from each physician's clientele base. Approximately 200 eligible subjects, men and women at least 18 years of age with stage I/II hypertension and stable type 2 diabetes mellitus, were to be enrolled on active treatment.
Pre-assignment details
192 participants started this single arm titration study. Participants remained in their group or were titrated at 3-week intervals depending on achievement their blood pressure goals.
Participants by arm
| Arm | Count |
|---|---|
| Active Treatmant Arm All participants started this arm with 20 mg olmesartan medoxomil (Olm). After 3 weeks participants were titrated to 40g Olm, if their blood pressure was not controlled. After 6 weeks they were titrated to the next step which now included Olm 40 mg + hydrochlorothiazide (HCTZ) 12.5 mg if their blood pressure was not controlled. After 9 weeks they were titrated to the next step which now included Olm + HCTZ 25 mg if their blood pressure was not controlled. | 192 |
| Total | 192 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Olm 40 mg | Adverse Event | 2 |
| Olm 40 mg | Other | 1 |
| Olm 40 mg | Protocol Violation | 1 |
| Olm 40 mg | Withdrawal by Subject | 1 |
| Olm 40 mg + Hydrochlorothiazide 12.5 mg | Adverse Event | 2 |
| Olm 40 mg + Hydrochlorothiazide 12.5 mg | Other | 1 |
| Olm 40 mg + Hydrochlorothiazide 12.5 mg | Protocol Violation | 1 |
| Olm 40 mg + Hydrochlorothiazide 12.5 mg | Withdrawal by Subject | 1 |
| Olm 40 mg + Hydrochlorothiazide 25 mg | Lost to Follow-up | 1 |
| Olm 40 mg + Hydrochlorothiazide 25 mg | Withdrawal by Subject | 1 |
| Olmesartan Medoxomil (Olm) 20 mg | Adverse Event | 1 |
| Olmesartan Medoxomil (Olm) 20 mg | Physician Decision | 1 |
| Olmesartan Medoxomil (Olm) 20 mg | Protocol Violation | 3 |
| Olmesartan Medoxomil (Olm) 20 mg | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Active Treatmant Arm |
|---|---|
| Age, Continuous | 58.1 years STANDARD_DEVIATION 10.3 |
| Diastolic BP | 90.0 mm Hg STANDARD_DEVIATION 10 |
| Heart rate | 76.4 beats/min STANDARD_DEVIATION 10.4 |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black/African American | 43 Participants |
| Race/Ethnicity, Customized Native Hawaiian/Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized White | 145 Participants |
| Region of Enrollment United States | 192 participants |
| Sex: Female, Male Female | 85 Participants |
| Sex: Female, Male Male | 107 Participants |
| Systolic BP | 158.1 mm Hg STANDARD_DEVIATION 12.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 192 | 5 / 182 | 3 / 173 | 6 / 144 |
| serious Total, serious adverse events | 0 / 192 | 0 / 182 | 1 / 173 | 0 / 144 |
Outcome results
Primary
Change From Baseline to Week 12 in Systolic BP (SBP) as Measured by 24-hour ABPM.
Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study.
Time frame: baseline and 12 weeks
Population: A total of 192 participants started. Eighteen dropped out. All Ambulatory Blood Pressure Monitoring (ABPM) Subjects (N=172) consisted of all subjects in the efficacy cohort who had a baseline and week 12 ABPM.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study Population | Change From Baseline to Week 12 in Systolic BP (SBP) as Measured by 24-hour ABPM. | -20.4 mm Hg | Standard Error 0.88 |
p-value: <0.0001One-sample t-test
Secondary
Change From Baseline to Week 12 in Ambulatory BP Measurement (Systolic)During the Last 2 Hours of the Last (Week 12) 24-hour Dosing Period.
Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study.
Time frame: baseline and 12 weeks
Population: A total of 192 participants started. Eighteen dropped out. All Ambulatory Blood Pressure Monitoring (ABPM) Subjects (N=172) consisted of all subjects in the efficacy cohort who had a baseline and week 12 ABPM. Of the 172 ABPM participants, only 169 had the required measurements for this outcome analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study Population | Change From Baseline to Week 12 in Ambulatory BP Measurement (Systolic)During the Last 2 Hours of the Last (Week 12) 24-hour Dosing Period. | -18.6 mm Hg | Standard Error 1.11 |
p-value: <0.0001One-sample t-test
Secondary
Change From Baseline to Week 12 in Ambulatory BP Measurement (Systolic)During the Last 4 Hours of the Last (Week 12 ) 24-hour Dosing Period.
Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study.
Time frame: baseline and 12 weeks
Population: A total of 192 participants started. Eighteen dropped out. All Ambulatory Blood Pressure Monitoring (ABPM) Subjects (N=172) consisted of all subjects in the efficacy cohort who had a baseline and week 12 ABPM.Of the 172 ABPM participants, only 171 had the required measurements for this outcome analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study Population | Change From Baseline to Week 12 in Ambulatory BP Measurement (Systolic)During the Last 4 Hours of the Last (Week 12 ) 24-hour Dosing Period. | -18.2 mm Hg | Standard Error 1 |
p-value: 0.0001one-sample t-test
Secondary
Change From Baseline to Week 12 in Ambulatory BP Measurement (Systolic)During the Last 6 Hours of the Last (Week 12 ) 24-hour Dosing Period.
Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study.
Time frame: baseline and 12 weeks
Population: A total of 192 participants started. Eighteen dropped out. All Ambulatory Blood Pressure Monitoring (ABPM) Subjects (N=172) consisted of all subjects in the efficacy cohort who had a baseline and week 12 ABPM. Of the 172 ABPM participants, only 171 had the required measurements
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study Population | Change From Baseline to Week 12 in Ambulatory BP Measurement (Systolic)During the Last 6 Hours of the Last (Week 12 ) 24-hour Dosing Period. | -18.6 mm Hg | Standard Error 0.92 |
Secondary
Change From Baseline to Week 12 in Mean 24-hour Ambulatory BP (Diastolic)
Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study.
Time frame: baseline and 12 weeks
Population: A total of 192 participants started. Eighteen dropped out. All Ambulatory Blood Pressure Monitoring (ABPM) Subjects (N=172) consisted of all subjects in the efficacy cohort who had a baseline and week 12 ABPM.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study Population | Change From Baseline to Week 12 in Mean 24-hour Ambulatory BP (Diastolic) | -11.1 mm Hg | Standard Error 0.54 |
p-value: <0.0001one-sample t-test
Secondary
Change From Baseline to Week 12 in Mean Daytime and Nighttime Ambulatory Blood Pressure Measurement (Systolic).
Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study.
Time frame: baseline and 12 weeks
Population: A total of 192 participants started. Eighteen dropped out. All Ambulatory Blood Pressure Monitoring (ABPM) Subjects (N=172) consisted of all subjects in the efficacy cohort who had a baseline and week 12 ABPM.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study Population | Change From Baseline to Week 12 in Mean Daytime and Nighttime Ambulatory Blood Pressure Measurement (Systolic). | Daytime | -22.3 mm Hg | Standard Error 1.05 |
| Overall Study Population | Change From Baseline to Week 12 in Mean Daytime and Nighttime Ambulatory Blood Pressure Measurement (Systolic). | Nighttime | -18.8 mm Hg | Standard Error 0.94 |
p-value: <0.0001one-sample t-test
Secondary
Change in Ambulatory Blood Pressure (Diastolic) From Baseline to Week 12 During the Last 2 Hours of the Last (Week 12 ) 24-hour Dosing Period.
Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study.
Time frame: baseline and 12 Weeks
Population: A total of 192 participants started. Eighteen dropped out. All Ambulatory Blood Pressure Monitoring (ABPM) Subjects (N=172) consisted of all subjects in the efficacy cohort who had a baseline and week 12 ABPM.Of the 172 participants, only 169 had the required measurements for this outcome analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Study Population | Change in Ambulatory Blood Pressure (Diastolic) From Baseline to Week 12 During the Last 2 Hours of the Last (Week 12 ) 24-hour Dosing Period. | -10.6 mm Hg | Standard Error 0.78 |
p-value: <0.0001one-sample t-test
Secondary
Change in Ambulatory BP (Diastolic) From Baseline to Week 12 During the Last (Week 12 ) 4 and 6 Hours of the Last 24-hour Dosing Period.
Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study.
Time frame: baseline and 12 weeks
Population: A total of 192 participants started. Eighteen dropped out. All Ambulatory Blood Pressure Monitoring (ABPM) Subjects (N=172) consisted of all subjects in the efficacy cohort who had a baseline and week 12 ABPM. Of the 172 ABPM participants, only 171 had the required measurements for this outcome analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study Population | Change in Ambulatory BP (Diastolic) From Baseline to Week 12 During the Last (Week 12 ) 4 and 6 Hours of the Last 24-hour Dosing Period. | 4 hours | -10.7 mm Hg | Standard Error 0.66 |
| Overall Study Population | Change in Ambulatory BP (Diastolic) From Baseline to Week 12 During the Last (Week 12 ) 4 and 6 Hours of the Last 24-hour Dosing Period. | 6 hours | -10.8 mm Hg | Standard Error 0.61 |
p-value: <0.0001one-sample t-test
Secondary
Change in Daytime and Nighttime Ambulatory Blood Pressure (Diastolic) From Baseline to Week 12
Participants had a 24-hour ambulatory blood pressure session at baseline and after 12 weeks of treatment. This outcome measure pooled all participants regardless of their titration history during the study.
Time frame: baseline and 12 weeks
Population: A total of 192 participants started. Eighteen dropped out. All Ambulatory Blood Pressure Monitoring (ABPM) Subjects (N=172) consisted of all subjects in the efficacy cohort who had a baseline and week 12 ABPM.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Study Population | Change in Daytime and Nighttime Ambulatory Blood Pressure (Diastolic) From Baseline to Week 12 | Daytime | -12.0 mm Hg | Standard Error 0.68 |
| Overall Study Population | Change in Daytime and Nighttime Ambulatory Blood Pressure (Diastolic) From Baseline to Week 12 | Nighttime | -10.2 mm Hg | Standard Error 0.55 |
p-value: <0.0001one-sample t-test