Hypertension
Conditions
Keywords
Aliskiren, Amlodipine, Non-responder to aliskiren
Brief summary
This study will assess the safety and efficacy of combination aliskiren/amlodipine in patients not adequately controlled with aliskiren alone
Interventions
DRUGAliskiren/Amlodipine 300/5 mg
Aliskiren/Amlodipine 300/5 mg tablet taken orally once a day with a glass of water.
DRUGAliskiren 300 mg
Aliskiren 300 mg tablet taken orally once a day with a glass of water.
DRUGAliskiren/Amlodipine 300/10 mg
Aliskiren/Amlodipine 300/10 mg taken orally once a day with a glass of water.
Placebo to Aliskiren tablet taken orally once a day.
Placebo to Aliskiren/Amlodipine taken orally once a day.
Sponsors
Novartis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Newly diagnosed patients or patients who have not been treated for hypertension within the 4 weeks prior to Visit 1 must have a mean sitting Diastolic Blood Pressure (msDBP) ≥ 95 mmHg and \< 110 mmHg at Visits 1 and 2 * Patients who have been treated for hypertension within the 4 weeks prior to - Visit 1 must have a msDBP ≥ 90 mmHg and \< 110 mmHg at Visit 2 * All patients must have a msDBP ≥ 90 mmHg and \< 110 mmHg at Visit 4
Exclusion criteria
* Severe hypertension * Pregnant or nursing (lactating) women * Women of child-bearing potential * Previous or current diagnosis of heart failure New York Heart Association (NYHA Class II-IV) * Serum potassium ≥ 5.3 mEq/L (mmol/L) at Visit 1 * Uncontrolled Type 1 or Type 2 diabetes mellitus * Hypersensitivity to renin inhibitors, calcium channel blockers, or to drugs with Similar chemical structures * History of hypertensive encephalopathy or cerebrovascular accident, or history of transient ischemic attack (TIA), myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of Study in the Mean Sitting Diastolic Blood Pressure (msDBP) | Baseline, End of Study (Week 8) | After the patient had been sitting for 5 minutes, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. The difference of the msDBP at baseline from the msDBP at 8 weeks was calculated using an Analysis of Covariance (ANCOVA) model with baseline as a covariate and treatment and region as two factors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to End of Study in the Mean Sitting Systolic Blood Pressure (msSBP) | Baseline, End of Study (Week 8) | After the patient had been sitting for 5 minutes, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. The difference of the msSBP at baseline from the msSBP at 8 weeks was calculated using an ANCOVA model with baseline as a covariate and treatment and region as two factors. |
| Number of Participants With Serious Adverse Events and Adverse Events | 8 weeks | The number of participants with any Serious Adverse Event and the number of participants with Adverse Events in any system organ class. Additional information about Adverse Events can be found in the Adverse Event Section. |
| Percentage of Participants Achieving Blood Pressure Control | 8 weeks | After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. Blood Pressure control was defined as having a mean sitting Diastolic Blood Pressure \<90 and a mean sitting Systolic Blood Pressure \<140. |
| Percentage of Participants Achieving a Diastolic Blood Pressure Response | 8 weeks | After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. A Diastolic Blood Pressure Response was defined as a mean sitting Diastolic Blood Pressure (msDBP) \<90 mmHg or a ≥ 10 mmHg reduction in msDBP from baseline. |
| Percentage of Participants Achieving a Systolic Blood Pressure Response | 8 weeks | After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. A Systolic Blood Pressure Response was defined as a mean sitting Systolic Blood Pressure (msSBP) \<140 mmHg or a ≥ 20 mmHg reduction in msSBP from baseline. |
Countries
Estonia, France, Iceland, India, Italy, Lithuania, South Korea, Spain, Venezuela
Participant flow
Pre-assignment details
This study consisted of a 7 day wash-out period and a 4 week single-blind run-in period prior to the 8 week double-blind period. 2 of the 820 randomized patients were randomized in error, are not included in the 818 participants enrolled in the double-blind period, did not receive study drug & are not included in the Safety and Full Analysis Sets.
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren 300 mg/Amlodipine 10 mg Participants received 1 Aliskiren/Amlodipine 300/10mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks. | 283 |
| Aliskiren 300 mg/Amlodipine 5 mg Participants received 1 Aliskiren/Amlodipine 300/5mg tablet + 1 Placebo to Aliskiren tablet once daily in the morning for 8 weeks. | 277 |
| Aliskiren 300 mg Participants received 1 Aliskiren 300 mg tablet + 1 Placebo to Aliskiren/Amlodipine tablet orally once daily in the morning for 8 weeks. | 260 |
| Total | 820 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 11 | 1 | 3 |
| Overall Study | Condition no longer required study drug | 1 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 9 |
| Overall Study | Lost to Follow-up | 3 | 1 | 0 |
| Overall Study | Patient withdrew consent | 3 | 2 | 3 |
| Overall Study | Protocol deviation | 2 | 1 | 1 |
| Overall Study | Randomized in error | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | Aliskiren 300 mg/Amlodipine 10 mg | Aliskiren 300 mg/Amlodipine 5 mg | Aliskiren 300 mg | Total |
|---|---|---|---|---|
| Age Continuous | 54.6 years STANDARD_DEVIATION 10.67 | 54.4 years STANDARD_DEVIATION 10.69 | 54.7 years STANDARD_DEVIATION 10.99 | 54.6 years STANDARD_DEVIATION 10.77 |
| Sex: Female, Male Female | 120 Participants | 101 Participants | 103 Participants | 324 Participants |
| Sex: Female, Male Male | 163 Participants | 176 Participants | 157 Participants | 496 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 | 26 / 282 | 6 / 276 | 1 / 260 |
| serious Total, serious adverse events | 3 / 282 | 4 / 276 | 1 / 260 |
Outcome results
Primary
Change From Baseline to End of Study in the Mean Sitting Diastolic Blood Pressure (msDBP)
After the patient had been sitting for 5 minutes, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. The difference of the msDBP at baseline from the msDBP at 8 weeks was calculated using an Analysis of Covariance (ANCOVA) model with baseline as a covariate and treatment and region as two factors.
Time frame: Baseline, End of Study (Week 8)
Population: Full Analysis Set (all randomized patients who received study drug). Three patients (1 in Aliskiren 300 mg/Amlodipine 10 mg group and 2 in the Aliskiren 300 mg/Amlodipine 5 mg group were excluded from the analysis due to lack of post-baseline assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren 300 mg/Amlodipine 10 mg | Change From Baseline to End of Study in the Mean Sitting Diastolic Blood Pressure (msDBP) | -13.07 mm Hg | Standard Error 0.463 |
| Aliskiren 300 mg/Amlodipine 5 mg | Change From Baseline to End of Study in the Mean Sitting Diastolic Blood Pressure (msDBP) | -10.54 mm Hg | Standard Error 0.467 |
| Aliskiren 300 mg | Change From Baseline to End of Study in the Mean Sitting Diastolic Blood Pressure (msDBP) | -5.84 mm Hg | Standard Error 0.48 |
Secondary
Change From Baseline to End of Study in the Mean Sitting Systolic Blood Pressure (msSBP)
After the patient had been sitting for 5 minutes, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. The difference of the msSBP at baseline from the msSBP at 8 weeks was calculated using an ANCOVA model with baseline as a covariate and treatment and region as two factors.
Time frame: Baseline, End of Study (Week 8)
Population: Full Analysis Set (all randomized patients who received study drug). Three patients (1 in Aliskiren 300 mg/Amlodipine 10 mg group and 2 in the Aliskiren 300 mg/Amlodipine 5 mg group were excluded from the analysis due to lack of post-baseline assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Aliskiren 300 mg/Amlodipine 10 mg | Change From Baseline to End of Study in the Mean Sitting Systolic Blood Pressure (msSBP) | -18.04 mm Hg | Standard Error 0.78 |
| Aliskiren 300 mg/Amlodipine 5 mg | Change From Baseline to End of Study in the Mean Sitting Systolic Blood Pressure (msSBP) | -14.43 mm Hg | Standard Error 0.788 |
| Aliskiren 300 mg | Change From Baseline to End of Study in the Mean Sitting Systolic Blood Pressure (msSBP) | -6.42 mm Hg | Standard Error 0.809 |
Secondary
Number of Participants With Serious Adverse Events and Adverse Events
The number of participants with any Serious Adverse Event and the number of participants with Adverse Events in any system organ class. Additional information about Adverse Events can be found in the Adverse Event Section.
Time frame: 8 weeks
Population: Safety Population consisted of all randomized participants who received study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Aliskiren 300 mg/Amlodipine 10 mg | Number of Participants With Serious Adverse Events and Adverse Events | Serious Adverse Events | 3 participants |
| Aliskiren 300 mg/Amlodipine 10 mg | Number of Participants With Serious Adverse Events and Adverse Events | Adverse Events | 85 participants |
| Aliskiren 300 mg/Amlodipine 5 mg | Number of Participants With Serious Adverse Events and Adverse Events | Serious Adverse Events | 4 participants |
| Aliskiren 300 mg/Amlodipine 5 mg | Number of Participants With Serious Adverse Events and Adverse Events | Adverse Events | 80 participants |
| Aliskiren 300 mg | Number of Participants With Serious Adverse Events and Adverse Events | Serious Adverse Events | 1 participants |
| Aliskiren 300 mg | Number of Participants With Serious Adverse Events and Adverse Events | Adverse Events | 59 participants |
Secondary
Percentage of Participants Achieving a Diastolic Blood Pressure Response
After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. A Diastolic Blood Pressure Response was defined as a mean sitting Diastolic Blood Pressure (msDBP) \<90 mmHg or a ≥ 10 mmHg reduction in msDBP from baseline.
Time frame: 8 weeks
Population: Full Analysis Set (all randomized patients who received study drug). Three patients (1 in Aliskiren 300 mg/Amlodipine 10 mg group and 2 in the Aliskiren 300 mg/Amlodipine 5 mg group were excluded from the analysis due to lack of post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren 300 mg/Amlodipine 10 mg | Percentage of Participants Achieving a Diastolic Blood Pressure Response | 83.6 Percentage of participants |
| Aliskiren 300 mg/Amlodipine 5 mg | Percentage of Participants Achieving a Diastolic Blood Pressure Response | 77.7 Percentage of participants |
| Aliskiren 300 mg | Percentage of Participants Achieving a Diastolic Blood Pressure Response | 51.5 Percentage of participants |
Secondary
Percentage of Participants Achieving a Systolic Blood Pressure Response
After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. A Systolic Blood Pressure Response was defined as a mean sitting Systolic Blood Pressure (msSBP) \<140 mmHg or a ≥ 20 mmHg reduction in msSBP from baseline.
Time frame: 8 weeks
Population: Full Analysis Set (all randomized patients who received study drug). Three patients (1 in Aliskiren 300 mg/Amlodipine 10 mg group and 2 in the Aliskiren 300 mg/Amlodipine 5 mg group were excluded from the analysis due to lack of post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren 300 mg/Amlodipine 10 mg | Percentage of Participants Achieving a Systolic Blood Pressure Response | 77.2 Percentage of participants |
| Aliskiren 300 mg/Amlodipine 5 mg | Percentage of Participants Achieving a Systolic Blood Pressure Response | 69.7 Percentage of participants |
| Aliskiren 300 mg | Percentage of Participants Achieving a Systolic Blood Pressure Response | 43.8 Percentage of participants |
Secondary
Percentage of Participants Achieving Blood Pressure Control
After the patient had been sitting for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic blood pressures were measured 3 times using the automatic Blood Pressure monitor and appropriate size cuff. The repeat sitting measurements were made at 1-2 minute intervals and the mean of these 3 sitting blood pressure measurements was used as the average sitting blood pressure for that visit. Blood Pressure control was defined as having a mean sitting Diastolic Blood Pressure \<90 and a mean sitting Systolic Blood Pressure \<140.
Time frame: 8 weeks
Population: Full Analysis Set (all randomized patients who received study drug). Three patients (1 in Aliskiren 300 mg/Amlodipine 10 mg group and 2 in the Aliskiren 300 mg/Amlodipine 5 mg group were excluded from the analysis due to lack of post-baseline assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aliskiren 300 mg/Amlodipine 10 mg | Percentage of Participants Achieving Blood Pressure Control | 65.5 Percentage of participants |
| Aliskiren 300 mg/Amlodipine 5 mg | Percentage of Participants Achieving Blood Pressure Control | 56.5 Percentage of participants |
| Aliskiren 300 mg | Percentage of Participants Achieving Blood Pressure Control | 31.5 Percentage of participants |