High Blood Pressure, Hypertension
Conditions
Keywords
Hypertension, valsartan, amlodipine, high blood pressure
Brief summary
The purpose of the study was to assess efficacy and safety of fixed dose combination of 5 mg amlodipine/80 mg valsartan compared to 160 mg valsartan monotherapy in lowering blood pressure in Taiwanese patients.
Interventions
DRUGAmlodipine 5mg/Valsartan 80 mg
Combination therapy of Amlodipine/Valsartan 5mg/80mg one dosage daily with one single tablet size for 8 weeks.
DRUGValsartan
For run-in period, Valsartan 80 mg daily in one dosage with one single tablet size for 4 weeks. Monotherapy for double blind treatment period in one dosage (Valsartan 160mg) daily with one single tablet size for 8 weeks
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants over 18 years of age with hypertension defined as sitting systolic blood pressure between 140 mmHg and 180 mmHg or sitting diastolic blood pressure between 90 mmHg and 120 mmHg. * High risk participants ( defined as having: (diabetes mellitus, chronic renal disease, Framingham 10-year risk score \>10%, established coronary artery disease (CAD), or CAD equivalents including carotid artery disease, peripheral arterial disease (PAD), abdominal aortic aneurysm (AAA))with hypertension defined as sitting systolic blood pressure between 130 mmHg and 180 mmHg or sitting diastolic blood pressure between 80 mmHg and 120 mmHg.
Exclusion criteria
* Known or suspected secondary hypertension * Known New York Heart Association (NYHA) functional class IV Heart Failure * History of myocardial infarction, transient ischemic attack or cerebrovascular accident within the preceding 3 months * Clinically significant valvular disease * Women who are pregnant, intend to become pregnant or are breastfeeding * Participants who have severe medical condition(s) that in the view of the Investigator prohibits participation in the study * Participants who have hypersensitivity to the investigational/ reference drug or any of the components in the formulation. * Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) From Office Blood Pressure Measurement | Baseline and 8 weeks | Two arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in mean sitting systolic blood pressure (msSBP) was calculated comparing the Week 8 readings to the readings taken at baseline. |
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) From Office Blood Pressure Measurement | Baseline and 8 weeks | Two arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in mean sitting diastolic blood pressure (msDBP) was calculated comparing the Week 8 readings to the readings taken at Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Systolic Blood Pressure (mSBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours | Baseline and 8 weeks | Validated automated ambulatory blood pressure monitors were dispensed to participants with instructions on correct use. Automated blood pressure readings were obtained every 15-30 minutes during waking hours and every 30-60 minutes during sleep for a total of 24 hours. The change in mean systolic blood pressure (mSBP) over 24 hours was measured from baseline to 8 weeks of treatment during the double-blind phase. |
| Change From Baseline in Mean Diastolic Blood Pressure (mDBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours After 8 Weeks of Treatment During the Double-blind Phase | Baseline and 8 weeks | Validated automated ambulatory blood pressure monitors were dispensed to participants with instructions on correct use. Automated blood pressure readings were obtained every 15-30 minutes during waking hours and every 30-60 minutes during sleep for a total of 24 hours. The change in mean diastolic blood pressure (mDBP) over 24 hours was measured from baseline to 8 weeks of treatment during the double-blind. |
| Number of Participants With Adverse Events During Double-blind Phase | 8 weeks | — |
Countries
Taiwan
Participant flow
Pre-assignment details
A 4 week run-in phase preceded the randomized, double-blind treatment phase of the study. During the run-in phase, participants took valsartan 80 mg daily before a meal. Sixty participants entered the run-in phase. Those participants who met the inclusion criteria entered the randomized, double-blind treatment phase.
Participants by arm
| Arm | Count |
|---|---|
| Amlodipine 5mg/Valsartan 80 mg During double-blind treatment period, patients randomized to combination therapy received daily one dosage (Amlodipine/Valsartan 5mg/80mg) with one single tablet size for 8 weeks. | 21 |
| Valsartan 160 mg In double blinded treatment period, patients randomized to this arm received 160 mg Valsartan once daily for 8 weeks. | 21 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Treatment | Adverse Event | 0 | 0 | 2 |
| Run-In Phase | Did not Meet Inclusion Criteria | 18 | 0 | 0 |
Baseline characteristics
| Characteristic | Amlodipine 5mg/Valsartan 80 mg | Valsartan 160 mg | Total |
|---|---|---|---|
| Age Continuous | 59.50 years STANDARD_DEVIATION 13.81 | 55.13 years STANDARD_DEVIATION 11.81 | 57.31 years STANDARD_DEVIATION 13.81 |
| Sex: Female, Male Female | 9 Participants | 8 Participants | 17 Participants |
| Sex: Female, Male Male | 12 Participants | 13 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 21 | 8 / 21 |
| serious Total, serious adverse events | 0 / 21 | 1 / 21 |
Outcome results
Primary
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) From Office Blood Pressure Measurement
Two arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in mean sitting diastolic blood pressure (msDBP) was calculated comparing the Week 8 readings to the readings taken at Baseline.
Time frame: Baseline and 8 weeks
Population: The Intent-to-Treat (ITT) Population includes all participants having taken at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amlodipine 5 mg/Valsartan 80 mg | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) From Office Blood Pressure Measurement | Baseline | 92.12 mmHg | Standard Deviation 10.84 |
| Amlodipine 5 mg/Valsartan 80 mg | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) From Office Blood Pressure Measurement | 8 weeks | 82.29 mmHg | Standard Deviation 8.74 |
| Amlodipine 5 mg/Valsartan 80 mg | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) From Office Blood Pressure Measurement | Change from baseline to 8 weeks | -9.83 mmHg | Standard Deviation 7.66 |
| Valsartan 160 mg | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) From Office Blood Pressure Measurement | Baseline | 89.98 mmHg | Standard Deviation 9.37 |
| Valsartan 160 mg | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) From Office Blood Pressure Measurement | 8 weeks | 86.73 mmHg | Standard Deviation 9.1 |
| Valsartan 160 mg | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) From Office Blood Pressure Measurement | Change from baseline to 8 weeks | -2.65 mmHg | Standard Deviation 6.75 |
Primary
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) From Office Blood Pressure Measurement
Two arterial blood pressure (BP) determinations were made after the participant was in the sitting position for 5 minutes according to the American Heart Association guidelines using a calibrated standard aneroid or mercury sphygmomanometer or a calibrated standard sphygmomanometer. The change in mean sitting systolic blood pressure (msSBP) was calculated comparing the Week 8 readings to the readings taken at baseline.
Time frame: Baseline and 8 weeks
Population: The Intent-to-Treat (ITT) Population includes all participants having taken at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amlodipine 5 mg/Valsartan 80 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) From Office Blood Pressure Measurement | Baseline | 150.26 mmHg | Standard Deviation 12.91 |
| Amlodipine 5 mg/Valsartan 80 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) From Office Blood Pressure Measurement | 8 weeks | 133.79 mmHg | Standard Deviation 14.63 |
| Amlodipine 5 mg/Valsartan 80 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) From Office Blood Pressure Measurement | Change from baseline to 8 weeks | -16.48 mmHg | Standard Deviation 15.53 |
| Valsartan 160 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) From Office Blood Pressure Measurement | Baseline | 141.14 mmHg | Standard Deviation 12.71 |
| Valsartan 160 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) From Office Blood Pressure Measurement | 8 weeks | 133.68 mmHg | Standard Deviation 12.73 |
| Valsartan 160 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) From Office Blood Pressure Measurement | Change from baseline to 8 weeks | -7.23 mmHg | Standard Deviation 11.6 |
Secondary
Change From Baseline in Mean Diastolic Blood Pressure (mDBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours After 8 Weeks of Treatment During the Double-blind Phase
Validated automated ambulatory blood pressure monitors were dispensed to participants with instructions on correct use. Automated blood pressure readings were obtained every 15-30 minutes during waking hours and every 30-60 minutes during sleep for a total of 24 hours. The change in mean diastolic blood pressure (mDBP) over 24 hours was measured from baseline to 8 weeks of treatment during the double-blind.
Time frame: Baseline and 8 weeks
Population: The Intent-to-Treat (ITT) Population includes all participants having taken at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amlodipine 5 mg/Valsartan 80 mg | Change From Baseline in Mean Diastolic Blood Pressure (mDBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours After 8 Weeks of Treatment During the Double-blind Phase | Baseline | 86.95 mmHg | Standard Deviation 14.14 |
| Amlodipine 5 mg/Valsartan 80 mg | Change From Baseline in Mean Diastolic Blood Pressure (mDBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours After 8 Weeks of Treatment During the Double-blind Phase | 8 weeks | 79.29 mmHg | Standard Deviation 10.7 |
| Amlodipine 5 mg/Valsartan 80 mg | Change From Baseline in Mean Diastolic Blood Pressure (mDBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours After 8 Weeks of Treatment During the Double-blind Phase | Change from baseline to 8 weeks | -7.67 mmHg | Standard Deviation 7.43 |
| Valsartan 160 mg | Change From Baseline in Mean Diastolic Blood Pressure (mDBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours After 8 Weeks of Treatment During the Double-blind Phase | Baseline | 87.90 mmHg | Standard Deviation 9.44 |
| Valsartan 160 mg | Change From Baseline in Mean Diastolic Blood Pressure (mDBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours After 8 Weeks of Treatment During the Double-blind Phase | 8 weeks | 82.94 mmHg | Standard Deviation 8.42 |
| Valsartan 160 mg | Change From Baseline in Mean Diastolic Blood Pressure (mDBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours After 8 Weeks of Treatment During the Double-blind Phase | Change from baseline to 8 weeks | -3.56 mmHg | Standard Deviation 7.7 |
Secondary
Change From Baseline in Mean Systolic Blood Pressure (mSBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours
Validated automated ambulatory blood pressure monitors were dispensed to participants with instructions on correct use. Automated blood pressure readings were obtained every 15-30 minutes during waking hours and every 30-60 minutes during sleep for a total of 24 hours. The change in mean systolic blood pressure (mSBP) over 24 hours was measured from baseline to 8 weeks of treatment during the double-blind phase.
Time frame: Baseline and 8 weeks
Population: The Intent-to-Treat (ITT) Population includes all participants having taken at least one dose of study medication.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Amlodipine 5 mg/Valsartan 80 mg | Change From Baseline in Mean Systolic Blood Pressure (mSBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours | Baseline | 144.38 mmHg | Standard Deviation 17.39 |
| Amlodipine 5 mg/Valsartan 80 mg | Change From Baseline in Mean Systolic Blood Pressure (mSBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours | 8 weeks | 129.67 mmHg | Standard Deviation 14.03 |
| Amlodipine 5 mg/Valsartan 80 mg | Change From Baseline in Mean Systolic Blood Pressure (mSBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours | Change from baseline to 8 weeks | -14.71 mmHg | Standard Deviation 11.64 |
| Valsartan 160 mg | Change From Baseline in Mean Systolic Blood Pressure (mSBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours | Baseline | 139.76 mmHg | Standard Deviation 13.46 |
| Valsartan 160 mg | Change From Baseline in Mean Systolic Blood Pressure (mSBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours | 8 weeks | 131.11 mmHg | Standard Deviation 12.39 |
| Valsartan 160 mg | Change From Baseline in Mean Systolic Blood Pressure (mSBP) From Ambulatory Blood Pressure Measurement (ABPM) Over 24 Hours | Change from baseline to 8 weeks | -6.39 mmHg | Standard Deviation 12.06 |
Secondary
Number of Participants With Adverse Events During Double-blind Phase
Time frame: 8 weeks
Population: Safety population included all patients who received at least one study medication during the study period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine 5 mg/Valsartan 80 mg | Number of Participants With Adverse Events During Double-blind Phase | Total AE | 9 Participants |
| Amlodipine 5 mg/Valsartan 80 mg | Number of Participants With Adverse Events During Double-blind Phase | At least one AE | 7 Participants |
| Amlodipine 5 mg/Valsartan 80 mg | Number of Participants With Adverse Events During Double-blind Phase | AE Not related to drug | 9 Participants |
| Valsartan 160 mg | Number of Participants With Adverse Events During Double-blind Phase | Total AE | 15 Participants |
| Valsartan 160 mg | Number of Participants With Adverse Events During Double-blind Phase | At least one AE | 11 Participants |
| Valsartan 160 mg | Number of Participants With Adverse Events During Double-blind Phase | AE Not related to drug | 15 Participants |