Essential Hypertension
Conditions
Keywords
Add on treatment, essential hypertension
Brief summary
Both Olmesartan (OLM)/Amlodipine (AML) combination and Hydrochlorothiazide (HCTZ) have proven to be efficacious and safe in lowering blood pressure, but may not always be sufficient. This study is to test efficacy and safety of the combination of OLM/AML and HCTZ in hypertensive patients whose blood pressure is not adequately controlled with OLM/AML alone. The following treatments will be included in the trial: OLM 40mg/AML 10mg; OLM 40mg/AML 10 mg/HCTZ 12.5 mg; OLM 40 mg/AML 10 mg/HCTZ 25 mg. The trial has four periods. The treatments that will be used are as follows: Period 1 - OLM 40mg/AML 10mg; Period 2 - OLM 40mg/AML 10mg or OLM 40mg/AML 10 mg/HCTZ 12.5 mg or OLM 40 mg/AML 10 mg/HCTZ 25 mg; Period 3 - OLM 40mg/AML 10 mg/HCTZ 12.5 mg; Period 4 - Period 3 responders: OLM 40mg/AML 10 mg/HCTZ 12.5 mg; Period 4 - Period 3 non-responders: OLM 40mg/AML 10 mg/HCTZ 12.5 mg or OLM 40 mg/AML 10 mg/HCTZ 25 mg
Interventions
DRUGOlmesartan medoxomil 40 mg - Amlodipine 10 mg
Oral tablets containing Olmesartan medoxomil-Amlodipine 40-10 mg, given once daily
DRUGOlmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 12.5mg
Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.
DRUGOlmesartan 40mg-Amlodipine 10mg-Hydrochlorothiazide 25mg
Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 2 Hydrochlorothiazide 12.5mg oral tablets. All tablets are given once a day.
DRUGOLM 40mg-AML 10mg-Hydrochlorothiazide 12.5mg
Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 1 Hydrochlorothiazide 12.5mg oral tablet + 1 Hydrochlorothiazide 12.5mg oral, placebo tablet. All tablets are given once a day.
DRUGOLM 40mg-AML 10mg-Hydrochlorothiazide 25mg
Coated, oral tablets containing Olmesartan 40mg-Amlodipine 10mg + 2 Hydrochlorothiazide 12.5mg oral tablet. All tablets are given once a day.
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female aged 18 years or older. * Mean trough seated systolic blood pressure (SeSBP) of ≥ 160/100 mmHg (SeSBP of ≥ 160 mmHg and seated diastolic blood pressure (SeDBP) ≥ 100 mmHg) at screening if not currently on antihypertensive medication (e.g. newly diagnosed subjects) OR: For subjects on monotherapy: mean trough SeSBP of ≥ 150/95 mmHg (SeSBP of ≥ 150 mmHg and SeDBP ≥ 95 mmHg) at screening OR: For subjects on any combination of antihypertensive medications that includes either hydrochlorothiazide or amlodipine or olmesartan for a duration of at least four weeks: mean trough SeSBP of ≥ 140/90 mmHg (SeSBP of ≥ 140 mmHg and SeDBP ≥ 90 mmHg) at screening OR: For subjects on any other combination of antihypertensive medications that includes neither hydrochlorothiazide, amlodipine nor olmesartan: mean trough SeSBP ≥ 160 mmHg, mean trough SeDBP ≥ 100mmHg, at the end of the taper-off period * Subject freely signs the Informed Consent Form (ICF) after the nature of the study and the disclosure of his/her data has been explained. * Female subjects of childbearing potential must be using adequate contraception (female of childbearing potential is defined as one who has not been postmenopausal for at least one year, or has not been surgically sterilised, or has not had a hysterectomy at least three months prior to the start of this study \[Visit 1\]). Females taking oral contraceptives should have been on therapy for at least three months. Adequate contraceptives include hormonal intra-uterine devices, hormonal contraceptives (oral, depot, patch or injectable), and double barrier methods such as condoms or diaphragms with spermicidal gel or foam. If a female becomes pregnant during the study, she has to be withdrawn immediately.
Exclusion criteria
* Female subjects of childbearing potential who are pregnant or lactating. * Subjects with serious disorders which may limit the ability to evaluate the efficacy or safety of the investigational products, including cerebrovascular, cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, haematological or oncological, neurological, and psychiatric diseases. The same applies for immunocompromised and/or neutropenic subjects. * Subjects having a history of the following within the last six months: myocardial infarction (MI), unstable angina pectoris, percutaneous coronary intervention, heart failure, hypertensive encephalopathy, cerebrovascular accident (stroke), or transient ischaemic attack. * Subjects with clinically significant abnormal laboratory values at Screening, including subjects with one or more of the following: * Aspartate aminotransferase (AST) \> 3 times upper limit of normal (ULN) * Alanine aminotransferase (ALT) \> 3 times ULN * Gamma-glutamyltransferase (GGT) \> 3 times ULN * Potassium above ULN (unless high value is due to haemolytic blood sample) * Subjects with secondary hypertension of any aetiology such as renal disease, phaeochromocytoma, or Cushing's syndrome. * Subjects with contraindication to olmesartan, amlodipine, hydrochlorothiazide, or any of the excipients. * Subjects with a mean SeSBP \> 200 mmHg or mean SeDBP \> 115 mmHg or bradycardia (heart rate \< 50 beats/min at rest documented by mean radial pulse rate \[PR\] or electrocardiogram \[ECG\]) at Screening (Visit 1) or immediately before taking Period I study medication (Visit 2).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Seated Diastolic Blood Pressure (SeDBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg | baseline (8 weeks) to 16 weeks | Three cuff blood pressure measurements were taken at each visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24-hour Diastolic Blood Pressure (DBP) Assessed by 24-hour Ambulatory Blood Pressure Measurement (ABPM). | Baseline (8 weeks) to 16 weeks | Three cuff blood pressure measurements were taken at each visit. |
| Change in Seated Systolic Blood Pressure (SeSBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg | baseline (8 weeks) to week 16 | Three cuff blood pressure measurements were taken at each visit. |
| Number of Subjects Achieving Blood Pressure (BP) Goal at Week 16. | baseline (week 8) to week 16 | Achieving blood pressure goal is defined as seated blood pressure \<140/90 mm Hg; 130/80 mm Hg for participants with diabetes and/or other chronic renal and/or chronic cardiovascular disease. Three cuff blood pressure measurements were taken at each visit. |
| In Non-responders, the Change in Seated Diastolic Blood Pressure Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. | week 24 to week 32 | Change in seated diastolic blood pressure from the beginning to the end of Period 4. Three cuff blood pressure measurements were taken at each visit. |
| Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. | Baseline (8 weeks) to 16 weeks | Three cuff blood pressure measurements were taken at each visit. |
| In Non-responders, the Number of Subject Meeting Their Blood Pressure Goals Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. | week 24 to week 32 | The number of non-responding participants who achieved their blood pressure goals at the end of Period 4. Achieving blood pressure goal is defined as seated blood pressure \<140/90 mm Hg; 130/80 mm Hg for participants with diabetes and/or other chronic renal and/or chronic cardiovascular disease. Three cuff blood pressure measurements were taken at each visit. |
| In Non-responders, the Change in 24-hour Diastolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. | Week 16 to week 32 | In non-responders, the change in 24-hour diastolic blood pressure assessed by 24-hour ambulatory blood pressure measurement from the beginning to the end of Period 4. |
| In Non-responders, the Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. | Week 16 to week 32 | In non-responders, the change in 24-hour systolic blood pressure assessed by 24-hour ambulatory blood pressure measurement from the beginning to the end of Period 4. |
| In Non-responders, the Change in Seated Systolic Blood Pressure Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. | week 24 to week 32 | Change in seated systolic blood pressure from the beginning to the end of Period 4. Three cuff blood pressure measurements were taken at each visit. |
Countries
Austria, Belgium, Bulgaria, Czechia, Denmark, France, Germany, Netherlands, Poland, Romania, Russia, Slovakia, Spain, Ukraine
Participant flow
Recruitment details
First participant visit was 29 April 2009. The last participant follow up was 07 September 2010
Pre-assignment details
The number of subjects entering Period 2 was only 808 because 1278 did not meet the entry criteria.
Participants by arm
| Arm | Count |
|---|---|
| Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg The participants in this arm received these 2 drugs for the 8-week, single-blind, run-in Period 1. Participants could then randomized to this same combination for an additional 8 weeks in the double-blind, Period 2. | 269 |
| OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 Participants could start receiving this combination in randomized, double-blind, 8- week Period 2. This combination was continued into single-blind, 8-week Period 3 for all participants entering Period 3 | 269 |
| OLM 40-AML 10-HCTZ 25 Participants could start receiving this combination in randomized, double-blind, 8- week Period 2. | 270 |
| Total | 808 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| 1-Single-blind, Run-in, Single-Treatment | Adverse Event | 49 | 0 | 0 | 0 | 0 | 0 |
| 1-Single-blind, Run-in, Single-Treatment | Lost to Follow-up | 4 | 0 | 0 | 0 | 0 | 0 |
| 1-Single-blind, Run-in, Single-Treatment | Other Reason | 13 | 0 | 0 | 0 | 0 | 0 |
| 1-Single-blind, Run-in, Single-Treatment | Protocol Violation | 22 | 0 | 0 | 0 | 0 | 0 |
| 1-Single-blind, Run-in, Single-Treatment | Withdrawal by Subject | 30 | 0 | 0 | 0 | 0 | 0 |
| 2-Randomized Double-blind 3 Treatments | Adverse Event | 4 | 2 | 3 | 0 | 0 | 0 |
| 2-Randomized Double-blind 3 Treatments | Lost to Follow-up | 1 | 0 | 2 | 0 | 0 | 0 |
| 2-Randomized Double-blind 3 Treatments | Other | 2 | 1 | 0 | 0 | 0 | 0 |
| 2-Randomized Double-blind 3 Treatments | Protocol Violation | 1 | 1 | 2 | 0 | 0 | 0 |
| 2-Randomized Double-blind 3 Treatments | Withdrawal by Subject | 1 | 2 | 1 | 0 | 0 | 0 |
| 3-Single-blind, Single Treatment | Adverse Event | 0 | 5 | 0 | 0 | 0 | 0 |
| 3-Single-blind, Single Treatment | Lost to Follow-up | 0 | 1 | 0 | 0 | 0 | 0 |
| 3-Single-blind, Single Treatment | Protocol Violation | 0 | 5 | 0 | 0 | 0 | 0 |
| 3-Single-blind, Single Treatment | Withdrawal by Subject | 0 | 4 | 0 | 0 | 0 | 0 |
| 4-Randomized Double-blind 2 Treatments | Adverse Event | 0 | 0 | 0 | 3 | 1 | 1 |
| 4-Randomized Double-blind 2 Treatments | Protocol Violation | 0 | 0 | 0 | 3 | 0 | 0 |
| 4-Randomized Double-blind 2 Treatments | Withdrawal by Subject | 0 | 0 | 0 | 3 | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg | OLM 40-AML 10-HCTZ 25 | OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 |
|---|---|---|---|---|
| Age, Continuous | 55.8 years STANDARD_DEVIATION 10.42 | 55.9 years STANDARD_DEVIATION 10.56 | 54.9 years STANDARD_DEVIATION 10.44 | 56.5 years STANDARD_DEVIATION 10.25 |
| Body Mass Index | 30.34 kg/m^2 STANDARD_DEVIATION 4.8 | 30.27 kg/m^2 STANDARD_DEVIATION 4.9 | 30.44 kg/m^2 STANDARD_DEVIATION 4.87 | 30.30 kg/m^2 STANDARD_DEVIATION 4.65 |
| Height | 170.3 cm STANDARD_DEVIATION 9.27 | 169.9 cm STANDARD_DEVIATION 9.74 | 170.4 cm STANDARD_DEVIATION 8.98 | 170.5 cm STANDARD_DEVIATION 9.11 |
| Obesity Body Mass Index < 30 kg/m^2 | 413 Participants | 138 Participants | 133 Participants | 142 Participants |
| Obesity Body Mass Index >= 30 kg/m^2 | 393 Participants | 131 Participants | 137 Participants | 125 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 807 Participants | 269 Participants | 269 Participants | 269 Participants |
| Sex: Female, Male Female | 339 Participants | 119 Participants | 116 Participants | 104 Participants |
| Sex: Female, Male Male | 469 Participants | 150 Participants | 154 Participants | 165 Participants |
| Weight | 88.2 kg STANDARD_DEVIATION 16.83 | 87.8 kg STANDARD_DEVIATION 18.14 | 88.5 kg STANDARD_DEVIATION 16.28 | 88.2 kg STANDARD_DEVIATION 16.03 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 113 / 2,204 | 7 / 269 | 7 / 270 |
| serious Total, serious adverse events | 18 / 2,204 | 15 / 269 | 3 / 270 |
Outcome results
Primary
Change in Seated Diastolic Blood Pressure (SeDBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg
Three cuff blood pressure measurements were taken at each visit.
Time frame: baseline (8 weeks) to 16 weeks
Population: The Full Analysis Set 1 included 806 randomized subjects who received at least 1 dose of double-blind study medication in Period II and provided at least 1 SeDBP measurement in Period II: 269 subjects in the OM/AML 40/10 mg group, 268 subjects in the OM/AML/HCTZ 40/10/12.5 mg group, and 269 subjects in the OM/AML/HCTZ 40/10/25 mg group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg | Change in Seated Diastolic Blood Pressure (SeDBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg | -6.1 mm Hg | Standard Error 0.55 |
| OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 | Change in Seated Diastolic Blood Pressure (SeDBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg | -7.1 mm Hg | Standard Error 0.55 |
| OLM 40-AML 10-HCTZ 25 | Change in Seated Diastolic Blood Pressure (SeDBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg | -8.9 mm Hg | Standard Error 0.55 |
p-value: 0.1187ANCOVA
p-value: <0.0001ANCOVA
Secondary
Change in 24-hour Diastolic Blood Pressure (DBP) Assessed by 24-hour Ambulatory Blood Pressure Measurement (ABPM).
Three cuff blood pressure measurements were taken at each visit.
Time frame: Baseline (8 weeks) to 16 weeks
Population: The Full Analysis Set 1 included 806 randomized subjects who received at least 1 dose of double-blind study medication in Period II and provided at least 1 SeDBP measurement in Period II: 269 subjects in the OM/AML 40/10 mg group, 268 subjects in the OM/AML/HCTZ 40/10/12.5 mg group, and 269 subjects in the OM/AML/HCTZ 40/10/25 mg group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg | Change in 24-hour Diastolic Blood Pressure (DBP) Assessed by 24-hour Ambulatory Blood Pressure Measurement (ABPM). | -2.1 mm Hg | Standard Error 0.52 |
| OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 | Change in 24-hour Diastolic Blood Pressure (DBP) Assessed by 24-hour Ambulatory Blood Pressure Measurement (ABPM). | -4.0 mm Hg | Standard Error 0.52 |
| OLM 40-AML 10-HCTZ 25 | Change in 24-hour Diastolic Blood Pressure (DBP) Assessed by 24-hour Ambulatory Blood Pressure Measurement (ABPM). | -5.3 mm Hg | Standard Error 0.52 |
p-value: 0.0009ANCOVA
p-value: <0.0001ANCOVA
Secondary
Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement.
Three cuff blood pressure measurements were taken at each visit.
Time frame: Baseline (8 weeks) to 16 weeks
Population: The Full Analysis Set 1 included 806 randomized subjects who received at least 1 dose of double-blind study medication in Period II and provided at least 1 SeDBP measurement in Period II: 269 subjects in the OM/AML 40/10 mg group, 268 subjects in the OM/AML/HCTZ 40/10/12.5 mg group, and 269 subjects in the OM/AML/HCTZ 40/10/25 mg group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg | Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. | -1.9 mm Hg | Standard Error 0.75 |
| OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 | Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. | -5.1 mm Hg | Standard Error 0.75 |
| OLM 40-AML 10-HCTZ 25 | Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. | -6.6 mm Hg | Standard Error 0.75 |
p-value: 0.0001ANCOVA
p-value: <0.0001ANCOVA
Secondary
Change in Seated Systolic Blood Pressure (SeSBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg
Three cuff blood pressure measurements were taken at each visit.
Time frame: baseline (8 weeks) to week 16
Population: The Full Analysis Set 1 included 806 randomized subjects who received at least 1 dose of double-blind study medication in Period II and provided at least 1 SeDBP measurement in Period II: 269 subjects in the OM/AML 40/10 mg group, 268 subjects in the OM/AML/HCTZ 40/10/12.5 mg group, and 269 subjects in the OM/AML/HCTZ 40/10/25 mg group.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg | Change in Seated Systolic Blood Pressure (SeSBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg | -6.9 mm Hg | Standard Error 0.76 |
| OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 | Change in Seated Systolic Blood Pressure (SeSBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg | -8.6 mm Hg | Standard Error 0.77 |
| OLM 40-AML 10-HCTZ 25 | Change in Seated Systolic Blood Pressure (SeSBP) of the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg vs. OM/AML 40/10 mg | -10.5 mm Hg | Standard Error 0.77 |
p-value: 0.0425ANCOVA
p-value: <0.0001ANCOVA
Secondary
In Non-responders, the Change in 24-hour Diastolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement.
In non-responders, the change in 24-hour diastolic blood pressure assessed by 24-hour ambulatory blood pressure measurement from the beginning to the end of Period 4.
Time frame: Week 16 to week 32
Population: The analysis population includes those participants who had blood pressure values at both the beginning and end of Period 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg | In Non-responders, the Change in 24-hour Diastolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. | -2.2 mm Hg | Standard Error 0.96 |
| OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 | In Non-responders, the Change in 24-hour Diastolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. | -4.4 mm Hg | Standard Error 0.81 |
p-value: 0.0253ANCOVA
Secondary
In Non-responders, the Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement.
In non-responders, the change in 24-hour systolic blood pressure assessed by 24-hour ambulatory blood pressure measurement from the beginning to the end of Period 4.
Time frame: Week 16 to week 32
Population: The analysis population includes those participants who had blood pressure values at both the beginning and end of Period 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg | In Non-responders, the Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. | -0.4 mm Hg | Standard Error 1.44 |
| OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 | In Non-responders, the Change in 24-hour Systolic Blood Pressure Assessed by 24-hour Ambulatory Blood Pressure Measurement. | -4.3 mm Hg | Standard Error 1.21 |
p-value: 0.0063ANCOVA
Secondary
In Non-responders, the Change in Seated Diastolic Blood Pressure Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg.
Change in seated diastolic blood pressure from the beginning to the end of Period 4. Three cuff blood pressure measurements were taken at each visit.
Time frame: week 24 to week 32
Population: The analysis population includes those participants who had blood pressure values at both the beginning and end of Period 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg | In Non-responders, the Change in Seated Diastolic Blood Pressure Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. | -6.7 mm Hg | Standard Error 0.84 |
| OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 | In Non-responders, the Change in Seated Diastolic Blood Pressure Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. | -7.9 mm Hg | Standard Error 0.69 |
p-value: 0.1611ANCOVA
Secondary
In Non-responders, the Change in Seated Systolic Blood Pressure Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg.
Change in seated systolic blood pressure from the beginning to the end of Period 4. Three cuff blood pressure measurements were taken at each visit.
Time frame: week 24 to week 32
Population: The analysis population includes those participants who had blood pressure values at both the beginning and end of Period 4.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg | In Non-responders, the Change in Seated Systolic Blood Pressure Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. | -5.5 mm Hg | Standard Error 1.1 |
| OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 | In Non-responders, the Change in Seated Systolic Blood Pressure Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. | -7.8 mm Hg | Standard Error 0.89 |
p-value: 0.0451ANCOVA
Secondary
In Non-responders, the Number of Subject Meeting Their Blood Pressure Goals Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg.
The number of non-responding participants who achieved their blood pressure goals at the end of Period 4. Achieving blood pressure goal is defined as seated blood pressure \<140/90 mm Hg; 130/80 mm Hg for participants with diabetes and/or other chronic renal and/or chronic cardiovascular disease. Three cuff blood pressure measurements were taken at each visit.
Time frame: week 24 to week 32
Population: The analysis population includes those participants who had blood pressure values at both the beginning and end of Period 4.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg | In Non-responders, the Number of Subject Meeting Their Blood Pressure Goals Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. | 31 Participants |
| OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 | In Non-responders, the Number of Subject Meeting Their Blood Pressure Goals Associated With the Triple Combinations OM/AML/HCTZ 40/10/12.5 and 40/10/25 mg. | 89 Participants |
p-value: 0.0412ANCOVA
Secondary
Number of Subjects Achieving Blood Pressure (BP) Goal at Week 16.
Achieving blood pressure goal is defined as seated blood pressure \<140/90 mm Hg; 130/80 mm Hg for participants with diabetes and/or other chronic renal and/or chronic cardiovascular disease. Three cuff blood pressure measurements were taken at each visit.
Time frame: baseline (week 8) to week 16
Population: The Full Analysis Set 1 included 806 randomized subjects who received at least 1 dose of double-blind study medication in Period II and provided at least 1 SeDBP measurement in Period II: 269 subjects in the OM/AML 40/10 mg group, 268 subjects in the OM/AML/HCTZ 40/10/12.5 mg group, and 269 subjects in the OM/AML/HCTZ 40/10/25 mg group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Olmesartan(OLM) 40 Mg-Amlodipine(AML) 10 mg | Number of Subjects Achieving Blood Pressure (BP) Goal at Week 16. | 65 Participants |
| OLM 40-AML 10-Hydrochlorothiazide (HCTZ) 12.5 | Number of Subjects Achieving Blood Pressure (BP) Goal at Week 16. | 79 Participants |
| OLM 40-AML 10-HCTZ 25 | Number of Subjects Achieving Blood Pressure (BP) Goal at Week 16. | 111 Participants |
p-value: 0.1939Cochran-Mantel-Haenszel
p-value: <0.0001Cochran-Mantel-Haenszel