Hypertension
Conditions
Keywords
hypertension, valsartan, amlodipine
Brief summary
This study will evaluate the efficacy and safety of valsartan and amlodipine in fixed dose combination in adults with moderate, inadequately controlled hypertension. There was an optional study extension for eligible patients who wanted to participate that contains the triple therapy (ie, hydrochlorothiazide+ amlodipine/valsartan).
Detailed description
Title of study extension: An open-label, multicenter extension to evaluate the efficacy and tolerability of a 4 week therapy with hydrochlorothiazide 12.5 mg plus amlodipine 10 mg/valsartan 160 mg in hypertensive patients not adequately responding to a 4 week therapy each with the combinations of olmesartan 20 mg plus amlodipine 10 mg followed by amlodipine 10 mg/valsartan 160 mg
Interventions
DRUGAmlodipine
Amlodipine supplied as 5 mg tablets, taken orally once a day during Treatment Phase 1 only.
DRUGOlmesartan medoxomil
Olmesartan medoxomil supplied as 10 mg tablets taken once a day during Treatment Phase 1 only.
DRUGAmlodipine+valsartan
Fixed-dose combination of amlodipine 10 mg plus valsartan 160 mg tablet taken orally once a day during Treatment Phase 2 and Extension Phase.
DRUGHydrochlorothiazide
Hydrochlorothiazide (HCTZ) 12.5 mg tablets taken once a day during the Extension Phase.
Sponsors
Novartis
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
for Core study: * Male or female patients (\>=18 years) * Females must be either post-menopausal for one year, surgically sterile or using effective contraceptive methods * Patients with essential hypertension (diastolic blood pressure \>=100 mmHg and \<110 mmHg) Inclusion Criteria for Extension: \- Patients had to have a msSBP \>= 140 mmHg and/or msDBP \>= 90 mmHg at week 8 ie, end of core study.
Exclusion criteria
for Core study: * Severe hypertension (diastolic blood pressure \>=110 mmHg or systolic blood pressure \>= 180 mmHg) * Pregnant or nursing women * Treated hypertensive patients with controlled hypertension under current therapy * A history of cardiovascular disease, including angina pectoris, myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, transient ischemic attack, stroke, and heart failure NYHA II - IV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Core Phase of the Study | Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) | The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. |
| Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Extension Phase of the Study | Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12) | The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sitting Pulse Rate During the Core Phase of the Study | Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) | Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position. |
| Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study | Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) | Normalized Blood Pressure was defined as a msSBP \< 140 mmHg and/or a msDBP \< 90 mmHg. |
| Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study | Baseline of Phase 2 (Week 4) to end of Phase 2 (Week 8) | Blood pressure response was defined as msSBP \< 140 mmHg or a 20 mmHg decrease in msSBP at the end of Phase 2 (Week 8) compared to Baseline in Phase 2 (week 4) or a msDBP \< 90 mmHg or a 10 mmHg decrease in msDBP at the end of Phase 2 compared to Baseline in Phase 2. |
| Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Extension Phase of the Study | Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12) | The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. |
| Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Core Phase of the Study | Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) | The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. |
| Change in Sitting Pulse Rate During the Extension Phase of the Study | Baseline Phase 3 (Week 8) to end of Phase 3 (week 12) | Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position. |
| Percentage of Patients Who Achieved Normalized Blood Pressure During the Extension Phase of the Study | Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12) | Normalized Blood Pressure was defined as a msSBP \< 140 mmHg and/or a msDBP \< 90 mmHg. |
| Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Extension Phase of the Study | Baseline of Phase 3 (Week 8) to end of Phase 3 (Week 12) | Blood pressure response was defined as msSBP \< 140 mmHg or a 20 mmHg decrease in msSBP at the end of Phase 3 compared to Baseline in Phase 3 or a msDBP \< 90 mmHg or a 10 mmHg decrease in msDBP at the end of Phase 3 compared to Baseline in Phase 3. |
| Change in Sitting Pulse Pressure During the Extension Phase of the Study | Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12) | Pulse pressure is systolic pressure (SP) minus diastolic pressure (DP). The arm in which the highest sitting DPs were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, SP and DP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. |
| Change in Sitting Pulse Pressure During the Core Phase of the Study | Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8) | Pulse pressure is systolic pressure (SP) minus diastolic pressure (DP). The arm in which the highest sitting DPs were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, SP and DP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Amlodipine(AML)+Olmesartan, AML+Valsartan, AML+Valsartan+HCTZ During the Treatment Phase 1, participants received 1 week of treatment with olmesartan 10 mg and amlodipine 5 mg once daily in free combination, followed by three weeks of treatment with olmesartan 20 mg plus amlodipine 10 mg once daily in free combination. During the Treatment Phase 2 participants received amlodipine 10 mg plus valsartan 160 mg for 4 weeks. During the Extension Phase, participants received 4 weeks treatment with amlodipine 10 mg plus valsartan 160 mg plus hydrochlorothiazide (HCTZ) 12.5 mg. | 257 |
| Total | 257 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Phase 1 - Amlodipine+Olmesartan | Administrative problems | 1 |
| Phase 1 - Amlodipine+Olmesartan | Adverse Event | 2 |
| Phase 1 - Amlodipine+Olmesartan | Lost to Follow-up | 2 |
| Phase 1 - Amlodipine+Olmesartan | Withdrawal by Subject | 1 |
| Phase 2 - Amlodipine+Valsartan | Adverse Event | 2 |
| Phase 2 - Amlodipine+Valsartan | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Amlodipine(AML)+Olmesartan, AML+Valsartan, AML+Valsartan+HCTZ |
|---|---|
| Age, Continuous Phase 1 - Amlodipine+olmesartan | 58.8 years STANDARD_DEVIATION 12.38 |
| Age, Continuous Phase 2 - Amlodipine+valsartan | 59.8 years STANDARD_DEVIATION 11.84 |
| Age, Continuous Phase 3 - Amlodipine+valsartan+HCTZ | 60.9 years STANDARD_DEVIATION 10.98 |
| Sex/Gender, Customized Phase 1 - Amlodipine+olmesartan - Female | 112 participants |
| Sex/Gender, Customized Phase 1 - Amlodipine+olmesartan - Male | 145 participants |
| Sex/Gender, Customized Phase 2 - Amlodipine+valsartan - Female | 76 participants |
| Sex/Gender, Customized Phase 2 - Amlodipine+valsartan - Male | 100 participants |
| Sex/Gender, Customized Phase 3 - Amlodipine+valsartan+HCTZ - Female | 32 participants |
| Sex/Gender, Customized Phase 3 - Amlodipine+valsartan+HCTZ - Male | 59 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 / 257 | 0 / 176 | 0 / 91 |
| serious Total, serious adverse events | 1 / 257 | 0 / 176 | 0 / 91 |
Outcome results
Primary
Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Core Phase of the Study
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Time frame: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8)
Population: Intent-to-treat population (ITT): All patients who took at least one dose of amlodipine plus valsartan who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine+Valsartan - Phase 2 | Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Core Phase of the Study | -9.13 mmHg | 95% Confidence Interval 1.97 |
Primary
Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Extension Phase of the Study
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Time frame: Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12)
Population: Safety population: All patients who took at least one dose of amlodipine 10 mg plus valsartan 160 mg plus HCTZ 12.5 mg.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Amlodipine+Valsartan - Phase 2 | Change in Mean Sitting Diastolic Blood Pressure (msDBP) During the Extension Phase of the Study | -5.22 mmHg |
Secondary
Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Core Phase of the Study
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Time frame: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8)
Population: Intent-to-treat population (ITT): All patients who took at least one dose of amlodipine plus valsartan who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine+Valsartan - Phase 2 | Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Core Phase of the Study | -7.87 mmHg | 95% Confidence Interval 9.48 |
Secondary
Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Extension Phase of the Study
The arm in which the highest sitting diastolic pressures were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, systolic/diastolic blood pressure were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Time frame: Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12)
Population: Safety population: All patients who took at least one dose of amlodipine 10 mg plus valsartan 160 mg plus HCTZ 12.5 mg.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Amlodipine+Valsartan - Phase 2 | Change in Mean Sitting Systolic Blood Pressure (msSBP) During the Extension Phase of the Study | -10.84 mmHg |
Secondary
Change in Sitting Pulse Pressure During the Core Phase of the Study
Pulse pressure is systolic pressure (SP) minus diastolic pressure (DP). The arm in which the highest sitting DPs were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, SP and DP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Time frame: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8)
Population: Intent-to-treat population (ITT): All patients who took at least one dose of amlodipine plus valsartan who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Amlodipine+Valsartan - Phase 2 | Change in Sitting Pulse Pressure During the Core Phase of the Study | 1.26 mmHg | 95% Confidence Interval 9.64 |
Secondary
Change in Sitting Pulse Pressure During the Extension Phase of the Study
Pulse pressure is systolic pressure (SP) minus diastolic pressure (DP). The arm in which the highest sitting DPs were found at study entry was the arm used for all subsequent readings. A calibrated sphygmomanometer and appropriate size cuff were used to measure arterial sitting blood pressure (BP) at trough with the arm supported at the level of the heart. At each study visit, after having the patient in a sitting position for at least 5 minutes, SP and DP were measured 3 times at 1-2 minute intervals. A mean was calculated from the 3 measurements. A negative change indicates improvement.
Time frame: Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12)
Population: Safety population: All patients who took at least one dose of amlodipine 10 mg plus valsartan 160 mg plus HCTZ 12.5 mg.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Amlodipine+Valsartan - Phase 2 | Change in Sitting Pulse Pressure During the Extension Phase of the Study | -5.62 mmHg |
Secondary
Change in Sitting Pulse Rate During the Core Phase of the Study
Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position.
Time frame: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8)
Population: Intent-to-treat population (ITT): All patients who took at least one dose of amlodipine plus valsartan who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Amlodipine+Valsartan - Phase 2 | Change in Sitting Pulse Rate During the Core Phase of the Study | -1.93 BPM (beats per minute) |
Secondary
Change in Sitting Pulse Rate During the Extension Phase of the Study
Pulse rate was measured once for 30 seconds just prior to blood pressure measurements in the sitting position.
Time frame: Baseline Phase 3 (Week 8) to end of Phase 3 (week 12)
Population: Safety population: All patients who took at least one dose of amlodipine 10 mg plus valsartan 160 mg plus HCTZ 12.5 mg.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Amlodipine+Valsartan - Phase 2 | Change in Sitting Pulse Rate During the Extension Phase of the Study | 0.09 BPM (beats per minute) |
Secondary
Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study
Blood pressure response was defined as msSBP \< 140 mmHg or a 20 mmHg decrease in msSBP at the end of Phase 2 (Week 8) compared to Baseline in Phase 2 (week 4) or a msDBP \< 90 mmHg or a 10 mmHg decrease in msDBP at the end of Phase 2 compared to Baseline in Phase 2.
Time frame: Baseline of Phase 2 (Week 4) to end of Phase 2 (Week 8)
Population: Intent-to-treat population (ITT): All patients who took at least one dose of amlodipine plus valsartan who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine+Valsartan - Phase 2 | Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study | msSBP response | 47.4 Percentage of participants |
| Amlodipine+Valsartan - Phase 2 | Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Core Phase of the Study | msDBP response | 73.1 Percentage of participants |
Secondary
Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Extension Phase of the Study
Blood pressure response was defined as msSBP \< 140 mmHg or a 20 mmHg decrease in msSBP at the end of Phase 3 compared to Baseline in Phase 3 or a msDBP \< 90 mmHg or a 10 mmHg decrease in msDBP at the end of Phase 3 compared to Baseline in Phase 3.
Time frame: Baseline of Phase 3 (Week 8) to end of Phase 3 (Week 12)
Population: Safety population: All patients who took at least one dose of amlodipine 10 mg plus valsartan 160 mg plus HCTZ 12.5 mg.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine+Valsartan - Phase 2 | Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Extension Phase of the Study | msSBP response | 61.5 Percentage of participants |
| Amlodipine+Valsartan - Phase 2 | Percentage of Patients Who Achieved a Protocol-defined Blood Pressure Response During the Extension Phase of the Study | msDBP response | 83.5 Percentage of participants |
Secondary
Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study
Normalized Blood Pressure was defined as a msSBP \< 140 mmHg and/or a msDBP \< 90 mmHg.
Time frame: Baseline Phase 2 (Week 4) to end of Phase 2 (Week 8)
Population: Intent-to-treat population (ITT): All patients who took at least one dose of amlodipine plus valsartan who had at least one primary efficacy parameter evaluation. Patients who dropped out were included in the ITT population if there was any BP measurement available; their last available blood pressure measurement was used for the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine+Valsartan - Phase 2 | Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study | msSBP < 140 mmHg | 44.6 Percentage of participants |
| Amlodipine+Valsartan - Phase 2 | Percentage of Patients Who Achieved Normalized Blood Pressure During the Core Phase of the Study | msDBP < 90 mmHg | 72.6 Percentage of participants |
Secondary
Percentage of Patients Who Achieved Normalized Blood Pressure During the Extension Phase of the Study
Normalized Blood Pressure was defined as a msSBP \< 140 mmHg and/or a msDBP \< 90 mmHg.
Time frame: Baseline Phase 3 (Week 8) to end of Phase 3 (Week 12)
Population: Safety population: All patients who took at least one dose of amlodipine 10 mg plus valsartan 160 mg plus HCTZ 12.5 mg.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Amlodipine+Valsartan - Phase 2 | Percentage of Patients Who Achieved Normalized Blood Pressure During the Extension Phase of the Study | msSBP < 140 mmHg | 59.3 Percentage of participants |
| Amlodipine+Valsartan - Phase 2 | Percentage of Patients Who Achieved Normalized Blood Pressure During the Extension Phase of the Study | msDBP < 90 mmHg | 83.5 Percentage of participants |