Essential Hypertension
Conditions
Keywords
Moderate-to-Severe Hypertension, Essential Hypertension, Combination Therapy, Fixed-Combination Dose
Brief summary
The study will evaluate the blood pressure lowering effects of two different dosages of the combination of olmesartan and hydrochlorothiazide in patients with moderate or severe high blood pressure.
Interventions
DRUGolmesartan medoxomil (OM)/hydrochlorothiazide (HCTZ) tablets and placebo
olmesartan medoxomil (OM)/hydrochlorothiazide (HCTZ) Tablet 40mg/0mg + 20mg/12.5mg matching placebo tablet once daily for 8 week
DRUGolmesartan medoxomil (OM)/hydrochlorothiazide (HCTZ) tablets
olmesartan medoxomil (OM)/hydrochlorothiazide (HCTZ) tablets 40mg/12.5mg + 20mg/12.5mg matching placebo tablet once daily for 8 weeks
DRUGolmesartan medoxomil/hydrochlorothiazide tablets
olmesartan medoxomil (OM)/hydrochlorothiazide (HCTZ) tablets 40mg/25mg + 20mg/12.5mg matching placebo tablet once daily for 8 weeks
Sponsors
Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female Europeans aged 18 years or older with moderate to severe hypertension (HTN)
Exclusion criteria
* Female patients of childbearing potential pregnant, lactating or planning to become pregnant during the trial period. * Patients with serious disorders which may limit the ability to evaluate the efficacy or safety of the study medication, including cerebrovascular, cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, haematological or oncological, neurological and psychiatric diseases. * Patients having a history of the following within the last six months: * myocardial infarction, * unstable angina pectoris, * percutaneous coronary intervention, * severe heart failure, * hypertensive encephalopathy, * cerebrovascular accident (stroke) or * transient ischaemic attack. * Patients with clinically significant abnormal laboratory values at screening. * Patients with secondary HTN.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 16 | 8 weeks, change = week 16 - week 8 | Change = Week 16 - Week 8 (baseline). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Trough Sitting Systolic Blood Pressure From Week 8(Baseline) to Week 16. | 8 weeks, change = week 16 - week 8 | Change = Week 16 - Week 8 (baseline). |
| Change in Mean Trough Sitting Systolic Blood Pressure From Week 8(Baseline) to Week 12. | 4 weeks, change = week 12 - week 8 | Change = Week 12 - Week 8 (baseline). |
| Number of Patients Achieving Target Blood Pressure at Week 16 | 8 weeks | Target Blood Pressure is diastolic blood pressure (dBP) \< 90 mmHg and systolic blood pressure (sBP) \< 140 mmHg for non-diabetics, and dBP \< 80 mmHg and sBP \< 130 mmHg for diabetics |
| Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 12. | 4 weeks, change = week 12 - week 8 | Change = Week 12 - Week 8 (baseline). |
| Change in Mean Daytime Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | 8 weeks, change = week 16 - week 8 | Change = Week 16 - Week 8 (baseline). |
| Change in Mean Night-time Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | 8 weeks, change = week 16 - week 8 | Change = Week 16 - Week 8 (baseline). |
| Change in Mean 24-hour Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | 8 weeks, change = week 16 - week 8 | Change = Week 16 - Week 8 (baseline). |
Countries
Bulgaria, Czechia, France, Germany, Poland, Spain, Ukraine
Participant flow
Recruitment details
78 investigative sites screened patients in Europe (19 in Czech Republic, 11 in Germany, 8 in Bulgaria, 5 in Spain, 20 in Ukraine, 1 in France and 14 in Poland). Sites were either hospitals or general practitioners. First patient in: 17 January 2007 Last patient out: 30 March 2008
Pre-assignment details
Trial is 2-week taper-off phase and 2 treatment periods. Period I-8-week open-label, OM 40mg. End of Period I, only non-responders randomised to Period II. Blood Pressure controlled patients discontinued. Period II-8-week double-blind four randomized treatment arms. Participant flow is Period II. 972 completed period I, 971 started period II.
Participants by arm
| Arm | Count |
|---|---|
| OM/HCTZ 40/25mg + 20/12.5 Matching Placebo olmesartan medoxomil/Hydrochlorothizaide 40/25mg tablets, once daily for 8 weeks | 140 |
| OM/HCTZ 40/12.5mg + 20/12.5 Matching Placebo olmesartan medoxomil/Hydrochlorothizaide 40/12.5mg tablets, once daily for 8 weeks | 278 |
| OM/HCTZ 20/12.5mg + 40/0 Matching Placebo olmesartan medoxomil/Hydrochlorothizaide 20/12.5mg tablets, once daily for 8 weeks | 279 |
| OM/HCTZ 40/0mg + 20/12.5 Matching Placebo olmesartan medoxomil/Hydrochlorothizaide 40/0mg tablets, once daily for 8 weeks | 274 |
| Total | 971 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 | 5 | 3 |
| Overall Study | conmed-BP-pulse-ABPM withdrawal criteria | 0 | 1 | 2 | 1 |
| Overall Study | Other | 1 | 1 | 3 | 0 |
| Overall Study | responder at visit 4 | 0 | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | OM/HCTZ 40/25mg + 20/12.5 Matching Placebo | OM/HCTZ 40/12.5mg + 20/12.5 Matching Placebo | OM/HCTZ 20/12.5mg + 40/0 Matching Placebo | OM/HCTZ 40/0mg + 20/12.5 Matching Placebo |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 138 Participants | 18 Participants | 38 Participants | 46 Participants | 36 Participants |
| Age, Categorical Between 18 and 65 years | 833 Participants | 122 Participants | 240 Participants | 233 Participants | 238 Participants |
| Age, Continuous | 54.5 years STANDARD_DEVIATION 9.24 | 55.2 years STANDARD_DEVIATION 8.17 | 53.7 years STANDARD_DEVIATION 9.77 | 55.2 years STANDARD_DEVIATION 9.47 | 54.1 years STANDARD_DEVIATION 8.92 |
| Race/Ethnicity, Customized European | 970.0 participants | 140 participants | 278 participants | 278 participants | 274 participants |
| Race/Ethnicity, Customized Other | 1.0 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Sex: Female, Male Female | 372 Participants | 52 Participants | 105 Participants | 100 Participants | 115 Participants |
| Sex: Female, Male Male | 599 Participants | 88 Participants | 173 Participants | 179 Participants | 159 Participants |
Outcome results
Primary
Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 16
Change = Week 16 - Week 8 (baseline).
Time frame: 8 weeks, change = week 16 - week 8
Population: Full Analysis Set-Last Observation Carried Forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OM/HCTZ 40/25mg + 20/12.5 Matching Placebo | Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 16 | -11.16 mm Hg | Standard Deviation 8.796 |
| OM/HCTZ 40/12.5mg + 20/12.5 Matching Placebo | Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 16 | -9.13 mm Hg | Standard Deviation 8.622 |
| OM/HCTZ 20/12.5mg + 40/0 Matching Placebo | Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 16 | -8.10 mm Hg | Standard Deviation 7.968 |
| OM/HCTZ 40/0mg + 20/12.5 Matching Placebo | Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 16 | -5.66 mm Hg | Standard Deviation 8.546 |
p-value: <0.000195% CI: [-6.97, -3.6]ANCOVA
p-value: <0.000195% CI: [-4.79, -2.03]ANCOVA
p-value: 0.178895% CI: [-2.32, 0.43]ANCOVA
Secondary
Change in Mean 24-hour Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16.
Change = Week 16 - Week 8 (baseline).
Time frame: 8 weeks, change = week 16 - week 8
Population: Full Analysis Set-Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OM/HCTZ 40/25mg + 20/12.5 Matching Placebo | Change in Mean 24-hour Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | -7.2 mm Hg | Standard Deviation 7.62 |
| OM/HCTZ 40/12.5mg + 20/12.5 Matching Placebo | Change in Mean 24-hour Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | -5.3 mm Hg | Standard Deviation 8.6 |
| OM/HCTZ 20/12.5mg + 40/0 Matching Placebo | Change in Mean 24-hour Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | -4.1 mm Hg | Standard Deviation 9.07 |
| OM/HCTZ 40/0mg + 20/12.5 Matching Placebo | Change in Mean 24-hour Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | -2.0 mm Hg | Standard Deviation 7.64 |
p-value: <0.000195% CI: [-6.78, -3.36]ANCOVA
p-value: <0.000195% CI: [-4.54, -1.78]ANCOVA
p-value: 0.145295% CI: [-2.43, 0.36]ANCOVA
Secondary
Change in Mean Daytime Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16.
Change = Week 16 - Week 8 (baseline).
Time frame: 8 weeks, change = week 16 - week 8
Population: Full Analysis Set-Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OM/HCTZ 40/25mg + 20/12.5 Matching Placebo | Change in Mean Daytime Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | -7.0 mm Hg | Standard Deviation 8.06 |
| OM/HCTZ 40/12.5mg + 20/12.5 Matching Placebo | Change in Mean Daytime Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | -5.5 mm Hg | Standard Deviation 9.1 |
| OM/HCTZ 20/12.5mg + 40/0 Matching Placebo | Change in Mean Daytime Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | -4.0 mm Hg | Standard Deviation 9.34 |
| OM/HCTZ 40/0mg + 20/12.5 Matching Placebo | Change in Mean Daytime Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | -1.8 mm Hg | Standard Deviation 8.39 |
p-value: <0.000195% CI: [-4.79, -1.87]ANCOVA
p-value: <0.000195% CI: [-6.79, -3.17]ANCOVA
p-value: 0.162995% CI: [-2.52, 0.42]ANCOVA
Secondary
Change in Mean Night-time Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16.
Change = Week 16 - Week 8 (baseline).
Time frame: 8 weeks, change = week 16 - week 8
Population: Full Analysis Set-Observed Cases
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OM/HCTZ 40/25mg + 20/12.5 Matching Placebo | Change in Mean Night-time Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | -7.9 mm Hg | Standard Deviation 9.51 |
| OM/HCTZ 40/12.5mg + 20/12.5 Matching Placebo | Change in Mean Night-time Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | -4.5 mm Hg | Standard Deviation 9.9 |
| OM/HCTZ 20/12.5mg + 40/0 Matching Placebo | Change in Mean Night-time Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | -4.2 mm Hg | Standard Deviation 10.61 |
| OM/HCTZ 40/0mg + 20/12.5 Matching Placebo | Change in Mean Night-time Ambulatory Blood Pressure Monitoring Diastolic Blood Pressure From Week 8(Baseline) to Week 16. | -2.3 mm Hg | Standard Deviation 8.47 |
p-value: <0.000195% CI: [-7.4, -3.62]ANCOVA
p-value: <0.000995% CI: [-4.12, -1.07]ANCOVA
p-value: 0.198595% CI: [-2.55, 0.53]ANCOVA
Secondary
Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 12.
Change = Week 12 - Week 8 (baseline).
Time frame: 4 weeks, change = week 12 - week 8
Population: Full Analysis Set-Last Observation Carried Forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OM/HCTZ 40/25mg + 20/12.5 Matching Placebo | Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 12. | -8.74 mm Hg | Standard Deviation 7.879 |
| OM/HCTZ 40/12.5mg + 20/12.5 Matching Placebo | Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 12. | -7.72 mm Hg | Standard Deviation 7.606 |
| OM/HCTZ 20/12.5mg + 40/0 Matching Placebo | Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 12. | -6.66 mm Hg | Standard Deviation 7.09 |
| OM/HCTZ 40/0mg + 20/12.5 Matching Placebo | Change in Mean Trough Sitting Diastolic Blood Pressure From Week 8(Baseline) to Week 12. | -4.47 mm Hg | Standard Deviation 7.197 |
p-value: <0.000195% CI: [-5.54, -2.6]ANCOVA
p-value: <0.000195% CI: [-4.39, -1.98]ANCOVA
p-value: 0.108195% CI: [-2.19, 0.22]ANCOVA
Secondary
Change in Mean Trough Sitting Systolic Blood Pressure From Week 8(Baseline) to Week 12.
Change = Week 12 - Week 8 (baseline).
Time frame: 4 weeks, change = week 12 - week 8
Population: Full Analysis Set-Last Observation Carried Forward
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OM/HCTZ 40/25mg + 20/12.5 Matching Placebo | Change in Mean Trough Sitting Systolic Blood Pressure From Week 8(Baseline) to Week 12. | -13.16 mm Hg | Standard Deviation 13.337 |
| OM/HCTZ 40/12.5mg + 20/12.5 Matching Placebo | Change in Mean Trough Sitting Systolic Blood Pressure From Week 8(Baseline) to Week 12. | -10.90 mm Hg | Standard Deviation 12.297 |
| OM/HCTZ 20/12.5mg + 40/0 Matching Placebo | Change in Mean Trough Sitting Systolic Blood Pressure From Week 8(Baseline) to Week 12. | -9.65 mm Hg | Standard Deviation 11.743 |
| OM/HCTZ 40/0mg + 20/12.5 Matching Placebo | Change in Mean Trough Sitting Systolic Blood Pressure From Week 8(Baseline) to Week 12. | -6.60 mm Hg | Standard Deviation 10.932 |
p-value: <0.000195% CI: [-9, -4.26]ANCOVA
p-value: <0.000195% CI: [-6.7, -2.81]ANCOVA
p-value: 0.081295% CI: [-3.66, 0.21]ANCOVA
Secondary
Change in Mean Trough Sitting Systolic Blood Pressure From Week 8(Baseline) to Week 16.
Change = Week 16 - Week 8 (baseline).
Time frame: 8 weeks, change = week 16 - week 8
Population: Full Analysis Set-Last Observation Carried Forward.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| OM/HCTZ 40/25mg + 20/12.5 Matching Placebo | Change in Mean Trough Sitting Systolic Blood Pressure From Week 8(Baseline) to Week 16. | -16.17 mm Hg | Standard Deviation 13.444 |
| OM/HCTZ 40/12.5mg + 20/12.5 Matching Placebo | Change in Mean Trough Sitting Systolic Blood Pressure From Week 8(Baseline) to Week 16. | -13.52 mm Hg | Standard Deviation 14.533 |
| OM/HCTZ 20/12.5mg + 40/0 Matching Placebo | Change in Mean Trough Sitting Systolic Blood Pressure From Week 8(Baseline) to Week 16. | -11.46 mm Hg | Standard Deviation 13.673 |
| OM/HCTZ 40/0mg + 20/12.5 Matching Placebo | Change in Mean Trough Sitting Systolic Blood Pressure From Week 8(Baseline) to Week 16. | -8.85 mm Hg | Standard Deviation 13.537 |
p-value: <0.000195% CI: [-10.13, -4.66]ANCOVA
p-value: <0.000195% CI: [-7.4, -2.91]ANCOVA
p-value: 0.025595% CI: [-4.79, -0.31]ANCOVA
Secondary
Number of Patients Achieving Target Blood Pressure at Week 16
Target Blood Pressure is diastolic blood pressure (dBP) \< 90 mmHg and systolic blood pressure (sBP) \< 140 mmHg for non-diabetics, and dBP \< 80 mmHg and sBP \< 130 mmHg for diabetics
Time frame: 8 weeks
Population: Full Analysis Set-Last Observation Carried Forward
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| OM/HCTZ 40/25mg + 20/12.5 Matching Placebo | Number of Patients Achieving Target Blood Pressure at Week 16 | 59 participants |
| OM/HCTZ 40/12.5mg + 20/12.5 Matching Placebo | Number of Patients Achieving Target Blood Pressure at Week 16 | 110 participants |
| OM/HCTZ 20/12.5mg + 40/0 Matching Placebo | Number of Patients Achieving Target Blood Pressure at Week 16 | 88 participants |
| OM/HCTZ 40/0mg + 20/12.5 Matching Placebo | Number of Patients Achieving Target Blood Pressure at Week 16 | 68 participants |
95% CI: [1.69, 4.21]Regression, Logistic
95% CI: [1.5, 3.24]Regression, Logistic
95% CI: [1.07, 2.25]Regression, Logistic