Essential Hypertension
Conditions
Keywords
Blood pressure, hypertension, Exforge, valsartan/amlodipine
Brief summary
This study assessed the efficacy and safety of the valsartan/amlodipine 160/5 mg single-pill combination in patients with uncomplicated essential hypertension not adequately controlled (MSDBP ≥90 mmHg and \<110 mmHg) on valsartan 160 mg alone.
Interventions
DRUGValsartan/amlodipine 160/5 mg
Valsartan/amlodipine 160/5mg film coated tablets taken orally once daily.
DRUGValsartan 160 mg
Valsartan 160 mg capsule taken orally once daily.
DRUGPlacebo
1 capsule or tablet taken orally once daily
Sponsors
Novartis
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
* Patients must give written informed consent * Male or female ages 18 or older and less than 86 years * Diagnosed as having essential diastolic hypertension, as follows: * Visit 2/Single-blind run-in entry, all participants MUST have a MSDBP ≥ 95 mmHg and \< 100 mmHg * At Visit 3/Core double-blind treatment period entry, all patients MUST have a MSDBP \>=90 mmHg and \<110 mmHg
Exclusion criteria
* Severe hypertension * Evidence of secondary form of hypertension (coarctation of the aorta, hyperaldosteronism, unilateral or bilateral renal artery stenosis, Cushing's disease, pheochromocytoma or polycystic kidney disease ) * Malignant hypertension * Administration of any agent indicated for the treatment of hypertension after Visit 1 * Known moderate or malignant retinopathy. * Known or suspected contraindications, including history of allergy or hypersensitivity to Angiotensin II Receptor Blockers (ARBs), Calcium Channel Blockers (CCBs), or to drugs with similar chemical structures * History of hypertensive encephalopathy, cerebrovascular accident, or transient ischemic attack, myocardial infarction or all types of revascularization, angina pectoris of any type, including unstable angina * History of heart failure Grade II-IV according to New York Heart Association (NYHA) classification * Second of third degree heart block regardless of the use of a pacemaker, concomitant potentially life-threatening arrhythmia or symptomatic arrhythmia Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Diastolic Blood Pressure (MSDBP) From Baseline to Week 8 Endpoint | Baseline and Week 8 | Three 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 the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from baseline in MSDBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and center (pooled as appropriate) as factors and centered baseline MSDBP as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Sitting Systolic Blood Pressure (MSSBP) From Baseline to Week 8 Endpoint | Baseline and Week 8 | Three 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 the MSSBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from baseline in MSSBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and center (pooled as appropriate) as factors and centered baseline MSSBP as a covariate |
| Percentage of Participants With a Diastolic Blood Pressure Response at 8 Week Endpoint | Baseline and Week 8 | The percentage of participants with a Diastolic Blood Pressure Response defined as the percentage of participants with a Mean Sitting Diastolic Blood Pressure (MSDBP) \< 90 mmHg or a \>= 10 mmHg reduction from baseline. |
| Percentage of Participants With Diastolic Blood Pressure Control at 8 Week Endpoint | Week 8 | The percentage of participants with Diastolic Blood Pressure Control defined as the percentage of participants with a Mean Sitting Diastolic Blood Pressure (MSDBP) \< 90 mmHg. |
| Percentage of Participants With Overall Blood Pressure Control at 8 Week Endpoint | Week 8 | The percentage of participants with Overall Blood Pressure Control defined as the percentage of participants with a Mean Sitting Systolic Blood Pressure (MSSBP)/Mean Sitting Diastolic Blood Pressure (MSDBP) \< 140/90 mmHg. |
Participant flow
Recruitment details
932 participants were entered into the single-blind valsartan 160 mg arm. 278 participants were discontinued from the single-blind arm. 654 participants were randomized into the double-blind treatment phase; 329 to the Valsartan/amlodipine arm and 325 to the valsartan alone arm.
Participants by arm
| Arm | Count |
|---|---|
| Valsartan/Amlodipine 160/5 mg One film-coated tablet Valsartan/amlodipine 160/5 mg and 1 capsule Placebo to Valsartan taken orally once daily at approximately 9:00 AM for 8 weeks. | 328 |
| Valsartan 160 mg One capsule Valsartan 160 mg and 1 tablet placebo to Valsartan/Amlodipine taken orally once daily at approximately 9:00 AM for 8 weeks | 323 |
| Total | 651 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Treatment Phase | Abnormal test procedure result(s) | 0 | 0 | 1 |
| Double-Blind Treatment Phase | Adverse Event | 0 | 2 | 2 |
| Double-Blind Treatment Phase | Lost to Follow-up | 0 | 0 | 1 |
| Double-Blind Treatment Phase | Protocol deviation | 0 | 0 | 1 |
| Double-Blind Treatment Phase | Unsatisfactory therapeutic effect | 0 | 0 | 1 |
| Double-Blind Treatment Phase | Withdrawal by Subject | 0 | 8 | 13 |
| Single-Blind Valsartan 160 mg | Abnormal Laboratory Value | 1 | 0 | 0 |
| Single-Blind Valsartan 160 mg | Abnormal Test Procedure Result(s) | 96 | 0 | 0 |
| Single-Blind Valsartan 160 mg | Administrative problems | 82 | 0 | 0 |
| Single-Blind Valsartan 160 mg | Adverse Event | 11 | 0 | 0 |
| Single-Blind Valsartan 160 mg | Condition no longer requires study drug | 45 | 0 | 0 |
| Single-Blind Valsartan 160 mg | Lost to Follow-up | 4 | 0 | 0 |
| Single-Blind Valsartan 160 mg | Unsatisfactory therapeutic effect | 7 | 0 | 0 |
| Single-Blind Valsartan 160 mg | Withdrawal by Subject | 32 | 0 | 0 |
Baseline characteristics
| Characteristic | Valsartan/Amlodipine 160/5 mg | Valsartan 160 mg | Total |
|---|---|---|---|
| Age Continuous | 52.9 years STANDARD_DEVIATION 9.47 | 53.1 years STANDARD_DEVIATION 9.41 | 53.0 years STANDARD_DEVIATION 9.43 |
| Sex: Female, Male Female | 141 Participants | 150 Participants | 291 Participants |
| Sex: Female, Male Male | 187 Participants | 173 Participants | 360 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 329 | 0 / 325 |
| serious Total, serious adverse events | 0 / 329 | 1 / 325 |
Outcome results
Primary
Change in Mean Sitting Diastolic Blood Pressure (MSDBP) From Baseline to Week 8 Endpoint
Three 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 the MSDBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from baseline in MSDBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and center (pooled as appropriate) as factors and centered baseline MSDBP as a covariate.
Time frame: Baseline and Week 8
Population: Full Analysis Set includes all randomized participants who had both baseline and at least one post-baseline efficacy measurement. Last Observation Carried Forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan/Amlodipine 160/5 mg | Change in Mean Sitting Diastolic Blood Pressure (MSDBP) From Baseline to Week 8 Endpoint | -10.3 mmHg | Standard Error 0.39 |
| Valsartan 160 mg | Change in Mean Sitting Diastolic Blood Pressure (MSDBP) From Baseline to Week 8 Endpoint | -6.6 mmHg | Standard Error 0.4 |
Secondary
Change in Mean Sitting Systolic Blood Pressure (MSSBP) From Baseline to Week 8 Endpoint
Three 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 the MSSBP was calculated comparing the Week 8 readings to the readings taken at Baseline. The change from baseline in MSSBP was analyzed using an analysis of covariance model (ANCOVA) with treatment and center (pooled as appropriate) as factors and centered baseline MSSBP as a covariate
Time frame: Baseline and Week 8
Population: Full Analysis Set includes all randomized participants who had both baseline and at least one post-baseline efficacy measurement. Last Observation Carried Forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Valsartan/Amlodipine 160/5 mg | Change in Mean Sitting Systolic Blood Pressure (MSSBP) From Baseline to Week 8 Endpoint | -14.9 mmHg | Standard Error 0.61 |
| Valsartan 160 mg | Change in Mean Sitting Systolic Blood Pressure (MSSBP) From Baseline to Week 8 Endpoint | -7.0 mmHg | Standard Error 0.61 |
Secondary
Percentage of Participants With a Diastolic Blood Pressure Response at 8 Week Endpoint
The percentage of participants with a Diastolic Blood Pressure Response defined as the percentage of participants with a Mean Sitting Diastolic Blood Pressure (MSDBP) \< 90 mmHg or a \>= 10 mmHg reduction from baseline.
Time frame: Baseline and Week 8
Population: Full Analysis Set includes all randomized participants who had both baseline and at least one post-baseline efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valsartan/Amlodipine 160/5 mg | Percentage of Participants With a Diastolic Blood Pressure Response at 8 Week Endpoint | 70.1 Percentage of Participants |
| Valsartan 160 mg | Percentage of Participants With a Diastolic Blood Pressure Response at 8 Week Endpoint | 52.6 Percentage of Participants |
Secondary
Percentage of Participants With Diastolic Blood Pressure Control at 8 Week Endpoint
The percentage of participants with Diastolic Blood Pressure Control defined as the percentage of participants with a Mean Sitting Diastolic Blood Pressure (MSDBP) \< 90 mmHg.
Time frame: Week 8
Population: Full Analysis Set includes all randomized participants who had both baseline and at least one post-baseline efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valsartan/Amlodipine 160/5 mg | Percentage of Participants With Diastolic Blood Pressure Control at 8 Week Endpoint | 65.9 Percentage of Participants |
| Valsartan 160 mg | Percentage of Participants With Diastolic Blood Pressure Control at 8 Week Endpoint | 50.8 Percentage of Participants |
Secondary
Percentage of Participants With Overall Blood Pressure Control at 8 Week Endpoint
The percentage of participants with Overall Blood Pressure Control defined as the percentage of participants with a Mean Sitting Systolic Blood Pressure (MSSBP)/Mean Sitting Diastolic Blood Pressure (MSDBP) \< 140/90 mmHg.
Time frame: Week 8
Population: Full Analysis Set includes all randomized participants who had both baseline and at least one post-baseline efficacy measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valsartan/Amlodipine 160/5 mg | Percentage of Participants With Overall Blood Pressure Control at 8 Week Endpoint | 61.3 Percentage of Participants |
| Valsartan 160 mg | Percentage of Participants With Overall Blood Pressure Control at 8 Week Endpoint | 39.3 Percentage of Participants |