Hypertension
Conditions
Keywords
Hypertension, valsartan, amlodipine, high blood pressure
Brief summary
This study evaluated the safety and efficacy of the fixed combination of valsartan/amlodipine in adult patients with mild to moderate hypertension.
Interventions
1 valsartan/amlodipine 80/5 mg tablet, 1 placebo capsule to match valsartan once daily
DRUGValsartan 80 mg
1 valsartan 80 mg capsule, 1 placebo tablet to match valsartan/amlodipine 80/5 mg once daily
DRUGValsartan 160 mg
1 valsartan 160 mg capsule, 1 placebo tablet to match valsartan/amlodipine 80/5 mg once daily
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Male or female outpatients \>= 18 years and \< 86 years * Patients with essential diastolic hypertension * At visit 1, the patient must have mean sitting diastolic blood pressure \>= 95 mmHg and \< 10 mmHg; patients treated with antihypertensive medication must have a mean sitting diastolic blood pressure \< 100 mmHg * At visit 2, patients must have a mean sitting diastolic blood pressure of \>= 95 mmHg and \< 100 mmHg * At visit 3, patients must have a mean sitting diastolic blood pressure of \>= 90 mmHg and \< 110 mmHg
Exclusion criteria
* Severe hypertension \>= 180/110 mmHg * Known or suspected contraindications, including a history of allergy or hypersensitivity to valsartan or amlodipine or to other drugs with similar chemical structures * Inability to discontinue all prior antihypertensive medications safely for a maximum period of up to 28 days prior to Visit 2 * History of hypertensive encephalopathy, cerebrovascular accident or transient ischemic attack, myocardial infarction or other types of revascularization * Malignant hypertension * All patients with Type I diabetes and those patients with Type 2 diabetes who are not well controlled based on the investigator's clinical judgment * Pregnant or nursing women * History of heart failure * Angina pectoris * Second or third degree heart block * Life threatening or symptomatic arrhythmias * Clinically significant valvular heart disease * Evidence of a secondary form of hypertension * Known or moderate malignant retinopathy * Evidence of hepatic disease * Evidence of renal impairment Other protocol-defined
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) | Baseline to end of study (Week 8) | Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 8) | Baseline to end of study (Week 8) | Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. |
| Percentage of Patients Achieving a Diastolic Blood Pressure Response at the End of the Study (Week 8) | Baseline to end of study (Week 8) | A diastolic blood pressure response was defined as a msDBP \< 90 mmHg or a ≥ 10 mmHg decrease compared to baseline at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. |
| Percentage of Patients Achieving Diastolic Blood Pressure Control at the End of the Study (Week 8) | End of study (Week 8) | Diastolic blood pressure control was defined as a msDBP \< 90 mmHg at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. |
| Percentage of Patients Achieving Overall Blood Pressure Control at the End of the Study (Week 8) | End of study (Week 8) | Overall blood pressure control rate was defined as a msSBP/msDBP \< 140/90 mmHg at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated. |
Countries
China
Participant flow
Recruitment details
A total of 1134 patients were enrolled into the single-blind period of the study, and 216 (19%) were discontinued. In total, 918 patients were randomized to the three treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Valsartan/Amlodipine 80/5 mg 1 valsartan/amlodipine 80/5 mg tablet, 1 placebo capsule to match valsartan once daily | 308 |
| Valsartan 80 mg 1 valsartan 80 mg capsule, 1 placebo tablet to match valsartan/amlodipine 80/5 mg once daily | 306 |
| Valsartan 160 mg 1 valsartan 160 mg capsule, 1 placebo tablet to match valsartan/amlodipine 80/5 mg once daily | 302 |
| Total | 916 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind | Adverse Event | 6 | 0 | 5 |
| Double-Blind | Lost to Follow-up | 3 | 4 | 2 |
| Double-Blind | Protocol deviation | 1 | 2 | 1 |
| Double-Blind | Subject withdrew consent | 4 | 6 | 9 |
| Double-Blind | Unsatisfactory therapeutic effect | 1 | 2 | 1 |
| Single-Blind | Adverse Event | 0 | 9 | 0 |
| Single-Blind | Lack of Efficacy | 0 | 5 | 0 |
| Single-Blind | Lost to Follow-up | 0 | 8 | 0 |
| Single-Blind | Protocol Violation | 0 | 16 | 0 |
| Single-Blind | Subject no longer requires study drug | 0 | 151 | 0 |
| Single-Blind | Withdrawal by Subject | 0 | 27 | 0 |
Baseline characteristics
| Characteristic | Valsartan/Amlodipine 80/5 mg | Valsartan 80 mg | Valsartan 160 mg | Total |
|---|---|---|---|---|
| Age Continuous | 51.6 years STANDARD_DEVIATION 10.8 | 51.7 years STANDARD_DEVIATION 8.9 | 51.2 years STANDARD_DEVIATION 9.6 | 51.5 years STANDARD_DEVIATION 9.8 |
| Sex: Female, Male Female | 127 Participants | 115 Participants | 104 Participants | 346 Participants |
| Sex: Female, Male Male | 181 Participants | 191 Participants | 198 Participants | 570 Participants |
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 | 0 / 308 | 0 / 307 | 0 / 303 |
| serious Total, serious adverse events | 4 / 308 | 0 / 307 | 4 / 303 |
Outcome results
Primary
Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8)
Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated.
Time frame: Baseline to end of study (Week 8)
Population: Full-set analysis population: All randomized patients who had a baseline and at least one post-baseline efficacy measurement. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan/Amlodipine 80/5 mg | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) | -10.8 mmHg | Standard Error 0.42 |
| Valsartan 80 mg | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) | -6.3 mmHg | Standard Error 0.42 |
| Valsartan 160 mg | Change in Mean Sitting Diastolic Blood Pressure (msDBP) From Baseline to End of Study (Week 8) | -7.2 mmHg | Standard Error 0.42 |
Secondary
Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 8)
Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated.
Time frame: Baseline to end of study (Week 8)
Population: Full-set analysis population population: All randomized patients who had a baseline and at least one post-baseline efficacy measurement. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan/Amlodipine 80/5 mg | Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 8) | -12.5 mmHg | Standard Error 0.61 |
| Valsartan 80 mg | Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 8) | -6.0 mmHg | Standard Error 0.62 |
| Valsartan 160 mg | Change in Mean Sitting Systolic Blood Pressure (msSBP) From Baseline to End of Study (Week 8) | -7.7 mmHg | Standard Error 0.62 |
Secondary
Percentage of Patients Achieving a Diastolic Blood Pressure Response at the End of the Study (Week 8)
A diastolic blood pressure response was defined as a msDBP \< 90 mmHg or a ≥ 10 mmHg decrease compared to baseline at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated.
Time frame: Baseline to end of study (Week 8)
Population: Full-set analysis population: All randomized patients who had a baseline and at least one post-baseline efficacy measurement. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valsartan/Amlodipine 80/5 mg | Percentage of Patients Achieving a Diastolic Blood Pressure Response at the End of the Study (Week 8) | 77.9 Percentage of patients |
| Valsartan 80 mg | Percentage of Patients Achieving a Diastolic Blood Pressure Response at the End of the Study (Week 8) | 57.8 Percentage of patients |
| Valsartan 160 mg | Percentage of Patients Achieving a Diastolic Blood Pressure Response at the End of the Study (Week 8) | 66.6 Percentage of patients |
Secondary
Percentage of Patients Achieving Diastolic Blood Pressure Control at the End of the Study (Week 8)
Diastolic blood pressure control was defined as a msDBP \< 90 mmHg at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated.
Time frame: End of study (Week 8)
Population: Full-set analysis population: All randomized patients who had a baseline and at least one post-baseline efficacy measurement. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valsartan/Amlodipine 80/5 mg | Percentage of Patients Achieving Diastolic Blood Pressure Control at the End of the Study (Week 8) | 74.4 Percentage of patients |
| Valsartan 80 mg | Percentage of Patients Achieving Diastolic Blood Pressure Control at the End of the Study (Week 8) | 53.6 Percentage of patients |
| Valsartan 160 mg | Percentage of Patients Achieving Diastolic Blood Pressure Control at the End of the Study (Week 8) | 64.2 Percentage of patients |
Secondary
Percentage of Patients Achieving Overall Blood Pressure Control at the End of the Study (Week 8)
Overall blood pressure control rate was defined as a msSBP/msDBP \< 140/90 mmHg at the end of the study (Week 8). Blood pressure (BP) was measured with a calibrated aneroid or mercury sphygmomanometer. The arm in which the highest sitting diastolic BP was found at study entry was used for all subsequent readings. At each visit, after the patient was in a sitting position for five minutes, systolic/diastolic BP was measured 3 times at 1-2-minute intervals. The mean of the 3 measurements was calculated.
Time frame: End of study (Week 8)
Population: Full-set analysis population: All randomized patients who had a baseline and at least one post-baseline efficacy measurement. For patients who did not complete the Week 8 assessment, a last observation carried forward (LOCF) approach was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valsartan/Amlodipine 80/5 mg | Percentage of Patients Achieving Overall Blood Pressure Control at the End of the Study (Week 8) | 70.5 Percentage of patients |
| Valsartan 80 mg | Percentage of Patients Achieving Overall Blood Pressure Control at the End of the Study (Week 8) | 44.1 Percentage of patients |
| Valsartan 160 mg | Percentage of Patients Achieving Overall Blood Pressure Control at the End of the Study (Week 8) | 58.6 Percentage of patients |