Hypertension
Conditions
Keywords
Hypertension, Angiotensin Receptor Blocker, Calcium Channel Blocker, Stage I and II Hypertension
Brief summary
This study will be conducted to assess the efficacy and safety of an amlodipine/olmesartan treatment regimen in stage 1 and stage 2 hypertensive subjects.
Interventions
DRUGAmlodipine
Tablets
DRUGOlmesartan medoxomil plus amlodipine
Tablets
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
* Males or females greater than or equal to 18 years of age * Patients with a mean seated systolic blood pressure (MSSBP) greater than or equal to 140 mm Hg but less than or equal to 199 mm Hg or a mean seated diastolic blood pressure (MSDBP) greater than or equal to 90 mm Hg and less than or equal to 109 mm Hg, following a period of taking only placebo * Patients with a mean daytime (8AM-4PM) systolic blood pressure greater than or equal to 135 mm Hg and less than or equal to 199 mm Hg and a mean daytime diastolic blood pressure less than or equal to 109 mm Hg as measured by an ambulatory blood pressure monitoring device (ABPM), after a period of taking only placebo * If female, must have negative serum pregnancy test at screening and be either post-menopausal (greater than or equal to 1 year), 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, coronary angioplasty, coronary artery bypass graft, or heart failure within the past 6 months * Patients with secondary hypertension of any etiology, such as renal disease, pheochromocytoma, or Cushing's syndrome * Type I diabetes. Patients with Type II diabetes on stable treatment, with fasting glucose \<160 mg/dl may enroll * Patients with hemodynamically significant cardiac valvular disease * Patients with clinically significant cardiac conduction defects, including second or third degree AV block, left bundle branch block, sick sinus syndrome, atrial fibrillation, atrial flutter, an accessory bypass tract, or any arrhythmia requiring medication
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Mean 24-hour Systolic Blood Pressure Measured by Ambulatory Monitoring | Baseline to 12 Weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Daytime and Nighttime Ambulatory Systolic Blood Pressure | Baseline to 12 weeks | — |
| Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg Group. | Baseline to end of week 3 | Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis. |
| Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg + Olmesartan 20 mg Group. | Baseline to end of week 6 | Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis. |
| Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg + Olmesartan 40 mg Group | Baseline to end of week 9 | Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis. |
| Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 10 mg + Olmesartan 40 mg Group | Baseline to end end of week 12 | Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at 18 US sites over 4 months (September 2007 to December 2007) from each physician's clientele base. Approximately 150 eligible participants, men and women at least 18 years of age with hypertension or uncontrolled hypertension on current medication, were to receive active treatment
Pre-assignment details
After placebo treatment, participants with a mean systolic blood pressure (SBP)≥140 mmHg and ≤199 mmHg or a mean diastolic BP (DBP)≥90 and ≤109 mmHg with a difference between mean SBPs ≤15 mmHg and a mean 8-hr daytime SBP of ≥135 mmHg and ≤199 mmHg, and mean 8-hr daytime DBP of \<110 mmHg by ambulatory BP monitoring were considered eligible.
Participants by arm
| Arm | Count |
|---|---|
| Amlodipine and Olmesartan, if Necessary Week 1-3 all participants: Amlodipine 5mg; Week 4-6 Amlodipine 5 mg/olmesartan 20 mg if mean SBP \>= 120/80 mm Hg; Week 7-9 Amlodipine 5 mg/ olmesartan 40 mg if mean SBP \>= 120/80 mm Hg; Week 10-12 Amlodipine 10 mg/olmesartan 40 mg if mean SBP \>= 120/80 mm Hg | 185 |
| Total | 185 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Weeks 10-12:Aml 10 mg +Olmesartan 40 mg | Adverse Event | 1 |
| Weeks 10-12:Aml 10 mg +Olmesartan 40 mg | Withdrawal by Subject | 1 |
| Weeks 1-3: Amlodipine (Aml) 5mg | Adverse Event | 1 |
| Weeks 4-6: Aml 5mg+Olmesartan 20 mg | Withdrawal by Subject | 2 |
| Weeks 7-9: Aml 5 mg + Olmesartan 40 mg | Adverse Event | 1 |
| Weeks 7-9: Aml 5 mg + Olmesartan 40 mg | Lost to Follow-up | 1 |
| Weeks 7-9: Aml 5 mg + Olmesartan 40 mg | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Amlodipine and Olmesartan, if Necessary |
|---|---|
| 24-Hour Ambulatory Diastolic Blood Pressure | 85.8 mm Hg STANDARD_DEVIATION 7.91 |
| 24-hour Ambulatory Systolic Blood Pressure | 144.6 mm Hg STANDARD_DEVIATION 10.88 |
| Age Continuous | 56.8 years STANDARD_DEVIATION 9.28 |
| Heart Rate | 75.1 beats/minute STANDARD_DEVIATION 10.82 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Asian | 14 Participants |
| Race/Ethnicity, Customized Black or African American | 26 Participants |
| Race/Ethnicity, Customized White | 144 Participants |
| Region of Enrollment United States | 185 participants |
| Sex: Female, Male Female | 80 Participants |
| Sex: Female, Male Male | 105 Participants |
| Stage of Hypertension Stage 1 | 82 Participants |
| Stage of Hypertension Stage 2 | 103 Participants |
| Systolic Blood Pressure | 158.2 mm Hg STANDARD_DEVIATION 12.63 |
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 | 8 / 185 | 23 / 180 | 11 / 161 | 12 / 134 |
| serious Total, serious adverse events | 0 / 185 | 0 / 180 | 1 / 161 | 1 / 134 |
Outcome results
Primary
Change From Baseline in Mean 24-hour Systolic Blood Pressure Measured by Ambulatory Monitoring
Time frame: Baseline to 12 Weeks
Population: The ambulatory blood pressure monitoring (ABPM) subset were subjects who received at least one dose of active study medication and had a baseline ABPM and end of study ABPM measurement.This = 172 participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Active Treatment Period | Change From Baseline in Mean 24-hour Systolic Blood Pressure Measured by Ambulatory Monitoring | -21.4 mm Hg | Standard Deviation 0.8 |
Comparison: The sample size of this study was not based on the statistical power consideration and was considered as sufficient for the evaluation of the efficacy and safety of the proposed olmesartan medoxomil-based treatment regimen.p-value: <0.0001one-sample t-test
Secondary
Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 10 mg + Olmesartan 40 mg Group
Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis.
Time frame: Baseline to end end of week 12
Population: ITT (efficacy cohort)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Active Treatment Period | Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 10 mg + Olmesartan 40 mg Group | -24.6 mm Hg | Standard Error 1.18 |
p-value: <0.0001one-sample t-test
Secondary
Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg Group.
Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis.
Time frame: Baseline to end of week 3
Population: ITT (efficacy cohort)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Active Treatment Period | Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg Group. | -10.1 mm Hg | Standard Deviation 0.97 |
p-value: <0.0001One-sample t-test
Secondary
Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg + Olmesartan 20 mg Group.
Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis.
Time frame: Baseline to end of week 6
Population: ITT (efficacy cohort)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Active Treatment Period | Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg + Olmesartan 20 mg Group. | -18.0 mm Hg | Standard Error 0.92 |
p-value: <0.0001one-sample t-test
Secondary
Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg + Olmesartan 40 mg Group
Change from study baseline in cuff systolic pressure (as measured by an Omron device) to the end of the treatment period. The Last Observation Carried Forwarded (LOCF) approach was used for the analysis.
Time frame: Baseline to end of week 9
Population: ITT (efficacy cohort)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Overall Active Treatment Period | Change From Baseline in Cuff Systolic Blood Pressure for the Amlodipine 5mg + Olmesartan 40 mg Group | -20.5 mm Hg | Standard Error 1.01 |
p-value: <0.0001One-sample t-test
Secondary
Change From Baseline in Daytime and Nighttime Ambulatory Systolic Blood Pressure
Time frame: Baseline to 12 weeks
Population: The ambulatory blood pressure monitoring (ABPM) subset were subjects who received at least one dose of active study medication and had a baseline ABPM and end of study ABPM measurement.This = 172 participants.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Overall Active Treatment Period | Change From Baseline in Daytime and Nighttime Ambulatory Systolic Blood Pressure | Daytime | -23.1 mm Hg | Standard Deviation 0.92 |
| Overall Active Treatment Period | Change From Baseline in Daytime and Nighttime Ambulatory Systolic Blood Pressure | Nighttime | -18.5 mm Hg | Standard Deviation 0.91 |
Comparison: Statistical analysis parameters apply to both the daytime and nighttime rows.p-value: <0.0001One-sample t-test