Severe Hypertension
Conditions
Keywords
Hypertension, Severe, LCZ696
Brief summary
This study assessed the safety, tolerability, and efficacy of LCZ696 in severe hypertensive Japanese patients
Detailed description
Summaries for treatment-emergent adverse events, serious adverse events and death were provided by the following actual treatment regimen (actual treatment patients received) in addition to all patients: LCZ696 200mg, 400mg, 400mg+other hypertensive medications. Summaries for others than above were provided by the following treatment regimen (determined by the maximal treatment patients received) in addition to all patients: LCZ696 200mg, 400mg, 400mg+other hypertensive medications.
Interventions
DRUGLCZ696
LCZ696 200 mg tablet once daily
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Satisfy office msSBP ≥180 mmHg or office msDBP ≥110 mmHg at baseline
Exclusion criteria
* Patients show msSBP ≥220 mmHg and/or msDBP ≥120 mmHg * History of angioedema, drug-related or otherwise, as reported by the patient * Patients unwilling or not able to discontinue safely the use of current antihypertensive medications during the study, as required by the protocol. * Patients have significant cardiovascular co-morbidities * Patients who previously entered a LCZ696 study and had been randomized or enrolled into the active drug treatment epoch. Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths | Week 8 | Adverse events, serious adverse events deaths were monitored from screening to week 8. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Successful Blood Pressure (BP) Control in msSBP/msDBP at End of Study | 8 weeks | Successful BP control in patients with severe hypertension at the end of study treatment was defined as follows: msSBP/msDBP\< 140/90 mmHg. |
| Percentage of Participants Achieving Successful msSBP Control at End of Study | 8 weeks | Successful msSBP control in patients with severe hypertension at the end of study treatment was defined as msSBP \<140 mmHg. |
| Change From Baseline in msSBP and msDBP at Week 8 | Baseline, 8 weeks | Sitting BP measurements were performed at screening through the end of study at every visit. Four separate sitting BP measurements were obtained with a full two-minute interval between measurements. The 4 measurements were summed and averaged, and then the baseline BP value was subtracted from the average value to get the change from baseline value. |
| Percentage of Participants With SBP Response at End of Study | Baseline, 8 weeks | SBP response was defined as \<140 mmHg or a reduction ≥ 20 mmHg from baseline. |
| Percentage of Participants With DBP Response at End of Study | Baseline, 8 weeks | DBP response was defined as \<90 mmHg or a reduction ≥ 10 mmHg from baseline. |
| Percentage of Participants Achieving Successful msDBP Control at End of Study | 8 weeks | Successful msDBP control in patients with severe hypertension at the end of study treatment was defined as msDBP \< 90 mmHg. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LCZ696 200 mg All participants were started on LCZ696 200 mg once daily on day 1. Participants who achieved mean sitting diastolic blood pressure (msDBP) of \< 100 mmHg and mean sitting systolic blood pressure (msSBP) of \< 160 mmHg at week 2 or a msDBP \< 90 mmHg and msSBP \< 140 mmHg at or after week 4 and for the duration of the study continued at 200 mg LCZ696 once daily. | 3 |
| LCZ696 400 mg All participants were started on LCZ696 200 mg once daily on day 1. For participants who did not achieve mean sitting diastolic blood pressure (msDBP) of \< 100 mmHg and mean sitting systolic blood pressure (msSBP) of \< 160 mmHg at week 2 or a msDBP \< 90 mmHg and msSBP \< 140 mmHg at or after week 4, and did not have any signs of safety concerns, the LCZ696 dose was increased to 400 mg once daily. | 11 |
| LCZ696 400 mg Plus Other Hypertension (HTN) Medications All participants were started on LCZ696 200 mg once daily on day 1. For participants who received LCZ696 400 mg and did not achieve msDBP \< 90 mmHg and msSBP \< 140 mmHg at or after week 4 and had no signs of safety concerns, another class of antihypertensive drugs (other than Angiotensin II receptor blockers or Angiotensin Converting Enzyme Inhibitor (ACEi) could be added, or the dose of concomitant antihypertensive drugs could be increased as per the package insert. Participants who received LCZ696 400 mg once daily did not change their dose for the remainder of the study. | 21 |
| Total | 35 |
Baseline characteristics
| Characteristic | LCZ696 200 mg | LCZ696 400 mg | LCZ696 400 mg Plus Other Hypertension (HTN) Medications | Total |
|---|---|---|---|---|
| Age, Continuous | 48.0 Years STANDARD_DEVIATION 4 | 56.0 Years STANDARD_DEVIATION 12.24 | 49.3 Years STANDARD_DEVIATION 7.57 | 51.3 Years STANDARD_DEVIATION 9.45 |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 3 Participants | 9 Participants | 21 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 35 | 2 / 32 | 5 / 21 | 10 / 35 |
| serious Total, serious adverse events | 1 / 35 | 0 / 32 | 0 / 21 | 1 / 35 |
Outcome results
Primary
Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths
Adverse events, serious adverse events deaths were monitored from screening to week 8.
Time frame: Week 8
Population: AE analysis was determined by actual treatment, i.e. the LCZ696 dose and use of newly introduced anti-HTN medication/dose escalation of base anti-HTN medication on the day in which the corresponding summary was targeting. Participants could be counted in more than one category. Other safety analysis was determined by the maximum treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCZ696 200 mg | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths | Serious Adverse Events | 2.9 Percentage of participants |
| LCZ696 200 mg | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths | Adverse Events (serious and non-serious) | 20.0 Percentage of participants |
| LCZ696 200 mg | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths | Deaths | 0 Percentage of participants |
| LCZ696 400 mg | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths | Adverse Events (serious and non-serious) | 12.5 Percentage of participants |
| LCZ696 400 mg | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths | Serious Adverse Events | 0 Percentage of participants |
| LCZ696 400 mg | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths | Deaths | 0 Percentage of participants |
| LCZ696 400 mg Plus Other Hypertension (HTN) Medications | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths | Adverse Events (serious and non-serious) | 33.3 Percentage of participants |
| LCZ696 400 mg Plus Other Hypertension (HTN) Medications | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths | Serious Adverse Events | 0 Percentage of participants |
| LCZ696 400 mg Plus Other Hypertension (HTN) Medications | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths | Deaths | 0 Percentage of participants |
| Total Participants | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths | Serious Adverse Events | 2.9 Percentage of participants |
| Total Participants | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths | Adverse Events (serious and non-serious) | 48.6 Percentage of participants |
| Total Participants | Percentage of Participants With Adverse Events (AEs), Serious Adverse Events and Deaths | Deaths | 0 Percentage of participants |
Secondary
Change From Baseline in msSBP and msDBP at Week 8
Sitting BP measurements were performed at screening through the end of study at every visit. Four separate sitting BP measurements were obtained with a full two-minute interval between measurements. The 4 measurements were summed and averaged, and then the baseline BP value was subtracted from the average value to get the change from baseline value.
Time frame: Baseline, 8 weeks
Population: Full Analysis Set: included all patients who entered the treatment epoch. This set was determined by the maximum treatment patients received, i.e. combination of the highest LCZ696 dose and use of newly introduced anti-HTN medication/dose escalation of base anti-HTN medication during the treatment epoch.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LCZ696 200 mg | Change From Baseline in msSBP and msDBP at Week 8 | msSBP | -48.83 mmHg | Standard Deviation 11.73 |
| LCZ696 200 mg | Change From Baseline in msSBP and msDBP at Week 8 | msDBP | -34.25 mmHg | Standard Deviation 7.378 |
| LCZ696 400 mg | Change From Baseline in msSBP and msDBP at Week 8 | msDBP | -16.98 mmHg | Standard Deviation 7.394 |
| LCZ696 400 mg | Change From Baseline in msSBP and msDBP at Week 8 | msSBP | -30.34 mmHg | Standard Deviation 15.054 |
| LCZ696 400 mg Plus Other Hypertension (HTN) Medications | Change From Baseline in msSBP and msDBP at Week 8 | msDBP | -23.08 mmHg | Standard Deviation 8.514 |
| LCZ696 400 mg Plus Other Hypertension (HTN) Medications | Change From Baseline in msSBP and msDBP at Week 8 | msSBP | -35.98 mmHg | Standard Deviation 15.229 |
| Total Participants | Change From Baseline in msSBP and msDBP at Week 8 | msDBP | -22.12 mmHg | Standard Deviation 9.167 |
| Total Participants | Change From Baseline in msSBP and msDBP at Week 8 | msSBP | -35.31 mmHg | Standard Deviation 15.348 |
Secondary
Percentage of Participants Achieving Successful msDBP Control at End of Study
Successful msDBP control in patients with severe hypertension at the end of study treatment was defined as msDBP \< 90 mmHg.
Time frame: 8 weeks
Population: Full Analysis Set: included all patients who entered the treatment epoch. This set was determined by the maximum treatment patients received, i.e. combination of the highest LCZ696 dose and use of newly introduced anti-HTN medication/dose escalation of base anti-HTN medication during the treatment epoch.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LCZ696 200 mg | Percentage of Participants Achieving Successful msDBP Control at End of Study | 66.7 Percentage of Participants |
| LCZ696 400 mg | Percentage of Participants Achieving Successful msDBP Control at End of Study | 36.4 Percentage of Participants |
| LCZ696 400 mg Plus Other Hypertension (HTN) Medications | Percentage of Participants Achieving Successful msDBP Control at End of Study | 52.4 Percentage of Participants |
| Total Participants | Percentage of Participants Achieving Successful msDBP Control at End of Study | 48.6 Percentage of Participants |
Secondary
Percentage of Participants Achieving Successful msSBP Control at End of Study
Successful msSBP control in patients with severe hypertension at the end of study treatment was defined as msSBP \<140 mmHg.
Time frame: 8 weeks
Population: Full Analysis Set: included all patients who entered the treatment epoch. This set was determined by the maximum treatment patients received, i.e. combination of the highest LCZ696 dose and use of newly introduced anti-HTN medication/dose escalation of base anti-HTN medication during the treatment epoch.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LCZ696 200 mg | Percentage of Participants Achieving Successful msSBP Control at End of Study | 100 Percentage of Participants |
| LCZ696 400 mg | Percentage of Participants Achieving Successful msSBP Control at End of Study | 45.5 Percentage of Participants |
| LCZ696 400 mg Plus Other Hypertension (HTN) Medications | Percentage of Participants Achieving Successful msSBP Control at End of Study | 66.7 Percentage of Participants |
| Total Participants | Percentage of Participants Achieving Successful msSBP Control at End of Study | 62.9 Percentage of Participants |
Secondary
Percentage of Participants With DBP Response at End of Study
DBP response was defined as \<90 mmHg or a reduction ≥ 10 mmHg from baseline.
Time frame: Baseline, 8 weeks
Population: Full Analysis Set: included all patients who entered the treatment epoch. This set was determined by the maximum treatment patients received, i.e. combination of the highest LCZ696 dose and use of newly introduced anti-HTN medication/dose escalation of base anti-HTN medication during the treatment epoch.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LCZ696 200 mg | Percentage of Participants With DBP Response at End of Study | 100 Percentage of Participants |
| LCZ696 400 mg | Percentage of Participants With DBP Response at End of Study | 100 Percentage of Participants |
| LCZ696 400 mg Plus Other Hypertension (HTN) Medications | Percentage of Participants With DBP Response at End of Study | 100 Percentage of Participants |
| Total Participants | Percentage of Participants With DBP Response at End of Study | 100 Percentage of Participants |
Secondary
Percentage of Participants With SBP Response at End of Study
SBP response was defined as \<140 mmHg or a reduction ≥ 20 mmHg from baseline.
Time frame: Baseline, 8 weeks
Population: Full Analysis Set: included all patients who entered the treatment epoch. This set was determined by the maximum treatment patients received, i.e. combination of the highest LCZ696 dose and use of newly introduced anti-HTN medication/dose escalation of base anti-HTN medication during the treatment epoch.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LCZ696 200 mg | Percentage of Participants With SBP Response at End of Study | 100 Percentage of Participants |
| LCZ696 400 mg | Percentage of Participants With SBP Response at End of Study | 81.8 Percentage of Participants |
| LCZ696 400 mg Plus Other Hypertension (HTN) Medications | Percentage of Participants With SBP Response at End of Study | 85.7 Percentage of Participants |
| Total Participants | Percentage of Participants With SBP Response at End of Study | 85.7 Percentage of Participants |
Secondary
Percentage of Participants With Successful Blood Pressure (BP) Control in msSBP/msDBP at End of Study
Successful BP control in patients with severe hypertension at the end of study treatment was defined as follows: msSBP/msDBP\< 140/90 mmHg.
Time frame: 8 weeks
Population: Full Analysis Set: included all patients who entered the treatment epoch. This set was determined by the maximum treatment patients received, i.e. combination of the highest LCZ696 dose and use of newly introduced anti-HTN medication/dose escalation of base anti-HTN medication during the treatment epoch.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LCZ696 200 mg | Percentage of Participants With Successful Blood Pressure (BP) Control in msSBP/msDBP at End of Study | 66.7 Percentage of Participants |
| LCZ696 400 mg | Percentage of Participants With Successful Blood Pressure (BP) Control in msSBP/msDBP at End of Study | 18.2 Percentage of Participants |
| LCZ696 400 mg Plus Other Hypertension (HTN) Medications | Percentage of Participants With Successful Blood Pressure (BP) Control in msSBP/msDBP at End of Study | 47.6 Percentage of Participants |
| Total Participants | Percentage of Participants With Successful Blood Pressure (BP) Control in msSBP/msDBP at End of Study | 40.0 Percentage of Participants |