Essential Hypertension
Conditions
Keywords
Olmesartan medoxomil, Hypertension
Brief summary
This study is to assess the safety and efficacy of an add-on treatment algorithm with olmesartan, hydrochlorothiazide and amlodipine in patients with mild to moderate hypertension.
Interventions
Olmesartan medoxomil oral tablets 20 mg for 4 weeks followed by, if necessary: Olmesartan medoxomil oral tablets 20 mg + hydrochlorothiazide oral tablets 12.5 mg for 4 weeks, followed by, if necessary: Olmesartan medoxomil oral tablets 20 mg + hydrochlorothiazide oral tablets 25 mg for 4 weeks, followed by, if necessary: Olmesartan medoxomil oral tablets 20 mg + hydrochlorothiazide oral tablets 25 mg + amlodipine oral tablets 5 mg for 4 weeks, followed by, if necessary: Olmesartan medoxomil oral tablets 20 mg + hydrochlorothiazide oral tablets 25 mg + amlodipine oral tablets 10 mg for 4 weeks. All study medications are to be taken once daily. The subject's participation completes when blood pressure goals are achieved.
Sponsors
Sankyo Pharma Gmbh
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
* Male and female patients age greater than or equal to 18 years with mild to moderate hypertension. * Pre-treated patients with normal or elevated blood pressure (BP) are eligible to participate if their pre-treatment medication can be withdrawn. At the end of the placebo run-in period sitting systolic BP greater than or equal to 140 and less than 180 mmHg and/or sitting diastolic BP greater than or equal to 90 and less than 110 mmHg at trough.
Exclusion criteria
* Female patients of childbearing potential must not be pregnant or lactating and must be using adequate contraception. * Patients with serious disorders which may limit the ability to evaluate the efficacy or safety of the test drug(s), including cardiovascular, renal, pulmonary, hepatic, gastrointestinal, endocrine/metabolic, haematological/oncological, neurological and psychiatric diseases. * Patients within the last 6 months having a history of myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, heart failure, cerebrovascular accident, or transient ischemic attack. * Patients with clinically significant elevations in laboratory values at Screening Visit. * Patients with secondary hypertension of any etiology, such as renal disease, pheochromocytoma, or Cushing's syndrome. * Patients with contraindications for olmesartan medoxomil, hydrochlorothiazide, and/or amlodipine besylate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Participants Treated to Target Blood Pressure Goals Overall and for Each Treatment Step From Baseline to Completion of Treatment During Which the Goal Was Achieved. | Baseline to ≤20 weeks | For non-diabetic participants the target seated blood pressure goals were: Systolic - ≤130 mm Hg; Diastolic - ≤85 mm Hg. For diabetic participants the target seated blood pressure goals were: Systolic - \<130 mm Hg; Diastolic - \<80 mm Hg. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Achieved Normalized Blood Pressure Overall and for Each Treatment From Baseline to Completion of the Treatment During Which Blood Pressure Goals Were Achieved | Baseline to ≤20 weeks | Normalized blood pressure is defined as a mean sitting systolic blood (sBP) pressure at trough of \<140 mmHg and mean sitting diastolic blood pressure (dBP)of \<90 mmHg for non-diabetic patients or a mean sitting sBP at trough of \<130 mmHg and mean sitting dBP \<80 mmHg for diabetic patients. |
| Percentage of Participants Who Were Diastolic Responders Overall and for Each Treatment From Baseline to the Completion of Treatment During Which Blood Pressure Goals Were Achieved. | Baseline to ≤20 weeks | Diastolic responders were defined as a participant who is a normaliser or has a lowering of the mean sitting diastolic blood pressure of ≥10 mmHg at trough. |
| Percentage of Participants Who Were Systolic Responders Overall and for Each Treatment From Baseline to the Completion of the Treatment During Which Blood Pressure Goals Were Achieved | Baseline to ≤20 weeks | Systolic responders defined as a participant who is a normaliser or has a lowering of the mean sitting systolic blood pressure of ≥20 mmHg at trough |
| Mean Change in Diastolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment | Baseline to ≤20 weeks | — |
| Mean Change in Systolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment | Baseline to ≤20 weeks | — |
Countries
Austria, Belgium, France, Germany, Italy, Netherlands, Portugal, Switzerland, United Kingdom
Participant flow
Recruitment details
The trial was conducted between April 2006 and April 2008 in 9 European countries at 58 investigational sites. The countries participating were: Austria, Belgium, France, Germany, Italy, The Netherlands, Portugal, Switzerland, and United Kingdom.
Participants by arm
| Arm | Count |
|---|---|
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed Olemesartan 20 mg to start. Hydrochlorothiazide 12.5 mg and then 25 mg was added, if necessary. If blood pressure goal was still not achieved, amlodipine 5 mg and then 10 mg were added, if needed. Thus, the maximum combination was olmesartan 20mg + hydrochlorothiazide 25mg + amlodipine 10mg. | 694 |
| Total | 694 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 21 |
| Overall Study | Did not meet entry criteria | 55 |
| Overall Study | Withdrawal by Subject | 17 |
Baseline characteristics
| Characteristic | Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed |
|---|---|
| Age Continuous | 58.16 years STANDARD_DEVIATION 12.06 |
| Body Mass Index | 28.86 kg/m^2 STANDARD_DEVIATION 4.69 |
| Ethnicity Asian | 3 Participants |
| Ethnicity Black | 13 Participants |
| Ethnicity Caucasian | 678 Participants |
| Region of Enrollment Austria | 35 participants |
| Region of Enrollment Belgium | 94 participants |
| Region of Enrollment France | 121 participants |
| Region of Enrollment Germany | 207 participants |
| Region of Enrollment Italy | 35 participants |
| Region of Enrollment Netherlands | 43 participants |
| Region of Enrollment Portugal | 12 participants |
| Region of Enrollment Switzerland | 6 participants |
| Region of Enrollment United Kingdom | 141 participants |
| Sex: Female, Male Female | 337 Participants |
| Sex: Female, Male Male | 357 Participants |
| Weight | 82.16 kg STANDARD_DEVIATION 16.09 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 293 / 694 |
| serious Total, serious adverse events | 7 / 694 |
Outcome results
Primary
The Percentage of Participants Treated to Target Blood Pressure Goals Overall and for Each Treatment Step From Baseline to Completion of Treatment During Which the Goal Was Achieved.
For non-diabetic participants the target seated blood pressure goals were: Systolic - ≤130 mm Hg; Diastolic - ≤85 mm Hg. For diabetic participants the target seated blood pressure goals were: Systolic - \<130 mm Hg; Diastolic - \<80 mm Hg.
Time frame: Baseline to ≤20 weeks
Population: 691 = the full analysis set (FAS). FAS consists of all participants who received trial medication and who had data from at least one post-baseline visit with regard to the primary efficacy parameter, i.e., both the systolic and the diastolic blood pressure (BP) had to be measured. N is reduced for each treatment as subjects attain BP goals.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | The Percentage of Participants Treated to Target Blood Pressure Goals Overall and for Each Treatment Step From Baseline to Completion of Treatment During Which the Goal Was Achieved. | Overall N=691 | 71.8 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | The Percentage of Participants Treated to Target Blood Pressure Goals Overall and for Each Treatment Step From Baseline to Completion of Treatment During Which the Goal Was Achieved. | OLM 20 mg N=688 | 12.3 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | The Percentage of Participants Treated to Target Blood Pressure Goals Overall and for Each Treatment Step From Baseline to Completion of Treatment During Which the Goal Was Achieved. | OLM 20 mg+HCTZ 12.5 mg N=580 | 16.4 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | The Percentage of Participants Treated to Target Blood Pressure Goals Overall and for Each Treatment Step From Baseline to Completion of Treatment During Which the Goal Was Achieved. | OLM 20 mg+HCTZ 25 mg N=446 | 19.2 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | The Percentage of Participants Treated to Target Blood Pressure Goals Overall and for Each Treatment Step From Baseline to Completion of Treatment During Which the Goal Was Achieved. | OLM 20 mg+HCTZ 25 mg+AML 5 mg N=296 | 14.9 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | The Percentage of Participants Treated to Target Blood Pressure Goals Overall and for Each Treatment Step From Baseline to Completion of Treatment During Which the Goal Was Achieved. | OLM 20 mg+HCTZ 25 mg+AML 10 mg N=176 | 8.5 Percentage of participants |
Secondary
Mean Change in Diastolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment
Time frame: Baseline to ≤20 weeks
Population: 691 = the full analysis set (FAS). FAS consists of all participants who received trial medication and who had data from at least one post-baseline visit with regard to the primary efficacy parameter, i.e., both the systolic and the diastolic blood pressure (BP) had to be measured. N is reduced for each treatment as subjects attain BP goals.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Mean Change in Diastolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment | Overall N=691 | -15.73 mm Hg | Standard Deviation 7.98 |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Mean Change in Diastolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment | OLM 20 mg N=688 | -6.44 mm Hg | Standard Deviation 7.53 |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Mean Change in Diastolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment | OLM 20 mg + HCTZ 12.5 mg N=580 | -10.15 mm Hg | Standard Deviation 7.54 |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Mean Change in Diastolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment | OLM 20 mg + HCTZ 25 mg N=446 | -13.04 mm Hg | Standard Deviation 7.67 |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Mean Change in Diastolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment | OLM 20 mg + HCTZ 25 mg + AML 5 mg N=296 | -14.03 mm Hg | Standard Deviation 8.27 |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Mean Change in Diastolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment | OLM 20 mg + HCTZ 25 mg + AML 10 mg N=176 | -14.47 mm Hg | Standard Deviation 8.86 |
Secondary
Mean Change in Systolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment
Time frame: Baseline to ≤20 weeks
Population: 691 = the full analysis set (FAS). FAS consists of all participants who received trial medication and who had data from at least one post-baseline visit with regard to the primary efficacy parameter, i.e., both the systolic and the diastolic blood pressure (BP) had to be measured. N is reduced for each treatment as subjects attain BP goals.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Mean Change in Systolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment | Overall N=691 | -29.58 mm Hg | Standard Deviation 13.52 |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Mean Change in Systolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment | OLM 20 mg N=688 | -11.97 mm Hg | Standard Deviation 11.42 |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Mean Change in Systolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment | OLM 20 mg + HCTZ 12.5 mg N=580 | -19.55 mm Hg | Standard Deviation 12.12 |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Mean Change in Systolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment | OLM 20 mg + HCTZ 25 mg N=446 | -24.51 mm Hg | Standard Deviation 13.14 |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Mean Change in Systolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment | OLM 20 mg + HCTZ 25 mg + AML 5 mg N=296 | -27.06 mm Hg | Standard Deviation 13.72 |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Mean Change in Systolic Blood Pressure Overall and for Each Treatment From Baseline to the Completion of the Treatment | OLM 20 mg + HCTZ 25 mg + AML 10 mg N=176 | -28.02 mm Hg | Standard Deviation 13.52 |
Secondary
Percentage of Participants Who Achieved Normalized Blood Pressure Overall and for Each Treatment From Baseline to Completion of the Treatment During Which Blood Pressure Goals Were Achieved
Normalized blood pressure is defined as a mean sitting systolic blood (sBP) pressure at trough of \<140 mmHg and mean sitting diastolic blood pressure (dBP)of \<90 mmHg for non-diabetic patients or a mean sitting sBP at trough of \<130 mmHg and mean sitting dBP \<80 mmHg for diabetic patients.
Time frame: Baseline to ≤20 weeks
Population: 691 = the full analysis set (FAS). FAS consists of all participants who received trial medication and who had data from at least one post-baseline visit with regard to the primary efficacy parameter, i.e., both the systolic and the diastolic blood pressure (BP) had to be measured. N is reduced for each treatment as subjects attain BP goals.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Achieved Normalized Blood Pressure Overall and for Each Treatment From Baseline to Completion of the Treatment During Which Blood Pressure Goals Were Achieved | Overall N=691 | 84.5 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Achieved Normalized Blood Pressure Overall and for Each Treatment From Baseline to Completion of the Treatment During Which Blood Pressure Goals Were Achieved | OLM 20 mg N=688 | 22.7 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Achieved Normalized Blood Pressure Overall and for Each Treatment From Baseline to Completion of the Treatment During Which Blood Pressure Goals Were Achieved | OLM 20 mg + HCTZ 12.5 mg N=580 | 31.1 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Achieved Normalized Blood Pressure Overall and for Each Treatment From Baseline to Completion of the Treatment During Which Blood Pressure Goals Were Achieved | OLM 20 mg + HCTZ 25 mg N=446 | 32.7 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Achieved Normalized Blood Pressure Overall and for Each Treatment From Baseline to Completion of the Treatment During Which Blood Pressure Goals Were Achieved | OLM 20 mg + HCTZ 25 mg + AML 5 mg N=296 | 23.9 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Achieved Normalized Blood Pressure Overall and for Each Treatment From Baseline to Completion of the Treatment During Which Blood Pressure Goals Were Achieved | OLM 20 mg + HCTZ 25 mg + AML 10 mg N=176 | 14.8 Percentage of participants |
Secondary
Percentage of Participants Who Were Diastolic Responders Overall and for Each Treatment From Baseline to the Completion of Treatment During Which Blood Pressure Goals Were Achieved.
Diastolic responders were defined as a participant who is a normaliser or has a lowering of the mean sitting diastolic blood pressure of ≥10 mmHg at trough.
Time frame: Baseline to ≤20 weeks
Population: 691 = the full analysis set (FAS). FAS consists of all participants who received trial medication and who had data from at least one post-baseline visit with regard to the primary efficacy parameter, i.e., both the systolic and the diastolic blood pressure (BP) had to be measured. N is reduced for each treatment as subjects attain BP goals.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Were Diastolic Responders Overall and for Each Treatment From Baseline to the Completion of Treatment During Which Blood Pressure Goals Were Achieved. | Overall N=691 | 93.3 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Were Diastolic Responders Overall and for Each Treatment From Baseline to the Completion of Treatment During Which Blood Pressure Goals Were Achieved. | OLM 20 mg N=688 | 36.6 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Were Diastolic Responders Overall and for Each Treatment From Baseline to the Completion of Treatment During Which Blood Pressure Goals Were Achieved. | OLM 20 mg + HCTZ 12.5 mg N=580 | 52.4 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Were Diastolic Responders Overall and for Each Treatment From Baseline to the Completion of Treatment During Which Blood Pressure Goals Were Achieved. | OLM 20 mg + HCTZ 25 mg N=446 | 48.6 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Were Diastolic Responders Overall and for Each Treatment From Baseline to the Completion of Treatment During Which Blood Pressure Goals Were Achieved. | OLM 20 mg + HCTZ 25 mg + AML 5 mg N=296 | 33.4 Percentage of participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Were Diastolic Responders Overall and for Each Treatment From Baseline to the Completion of Treatment During Which Blood Pressure Goals Were Achieved. | OLM 20 mg + HCTZ 25 mg + AML 10 mg N=176 | 20.4 Percentage of participants |
Secondary
Percentage of Participants Who Were Systolic Responders Overall and for Each Treatment From Baseline to the Completion of the Treatment During Which Blood Pressure Goals Were Achieved
Systolic responders defined as a participant who is a normaliser or has a lowering of the mean sitting systolic blood pressure of ≥20 mmHg at trough
Time frame: Baseline to ≤20 weeks
Population: 691 = the full analysis set (FAS). FAS consists of all participants who received trial medication and who had data from at least one post-baseline visit with regard to the primary efficacy parameter, i.e., both the systolic and the diastolic blood pressure (BP) had to be measured. N is reduced for each treatment as subjects attain BP goals.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Were Systolic Responders Overall and for Each Treatment From Baseline to the Completion of the Treatment During Which Blood Pressure Goals Were Achieved | Overall N=691 | 92.6 Percentage of Participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Were Systolic Responders Overall and for Each Treatment From Baseline to the Completion of the Treatment During Which Blood Pressure Goals Were Achieved | OLM 20 mg N=688 | 34.2 Percentage of Participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Were Systolic Responders Overall and for Each Treatment From Baseline to the Completion of the Treatment During Which Blood Pressure Goals Were Achieved | OLM 20 mg + HCTZ 12.5 mg N=580 | 49.6 Percentage of Participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Were Systolic Responders Overall and for Each Treatment From Baseline to the Completion of the Treatment During Which Blood Pressure Goals Were Achieved | OLM 20 mg + HCTZ 25 mg N=446 | 46.6 Percentage of Participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Were Systolic Responders Overall and for Each Treatment From Baseline to the Completion of the Treatment During Which Blood Pressure Goals Were Achieved | OLM 20 mg + HCTZ 25 mg + AML 5 mg N=296 | 33.3 Percentage of Participants |
| Olmesartan+Hydrochlorothiazide,if Needed+Amlodipine, if Needed | Percentage of Participants Who Were Systolic Responders Overall and for Each Treatment From Baseline to the Completion of the Treatment During Which Blood Pressure Goals Were Achieved | OLM 20 mg + HCTZ 25 mg + AML 10 mg N=176 | 20.5 Percentage of Participants |