Hypertension With Renal Dysfunction
Conditions
Keywords
Hypertension, Renal dysfunction, LCZ696
Brief summary
This study assessed the safety, tolerability, and efficacy of LCZ696 in hypertensive patients with renal dysfunction.
Interventions
DRUGLCZ696
100 mg, 200 mg, 400 mg tablets.
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
* Renal findings: Hypertensive patients with renal dysfunction and stable renal condition at least 4 weeks before screening visit. * Satisfy office msSBP ≥140 mmHg and \<180 mmHg at baseline.
Exclusion criteria
* Patients show msDBP ≥110 mmHg and/or msSBP ≥180 mmHg. * History of angioedema, drug-related or otherwise, as reported by the patient. * Any other following renal disorder: * Patients show eGFR \< 15mL/min/1.73m\^2 * Patients on dialysis * 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 Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) | 8 weeks | Percentage of patients with total adverse events, serious adverse events and death were reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 8 | baseline, 8 weeks | — |
| Percentage of Participants Achieving a Successful BP Control at Week 8 | 8 weeks | A successful BP control was defined as msSBP \<130 mmHg and msDBP \<80 mmHg |
| Percentage of Participants Achieving SBP Control at Week 8 | 8 weeks | SBP control was defined as msSBP \<130 mmHg. |
| Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) 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 were obtained with a full two-minute interval between measurements. |
| Percentage of Participants Achieving a Successful Response Rate in msSBP at Week 8 | 8 weeks | Successful response rate was defined as msSBP \<130 mmHg or a reduction of ≥20 mmHg from baseline |
| Percentage of Participants Achieving a Successful Response Rate in msDBP at Week 8 | 8 weeks | Successful response rate was defined as msDBP \<80 mmHg or a reduction of ≥10 mmHg from baseline. |
| Percentage of Participants Achieving DBP Control at Week 8 | 8 weeks | DBP control was defined as msDBP \<80 mmHg. |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LCZ696 100 mg All participants were started on LCZ696 100 mg once daily on day 1. | 6 |
| LCZ696 200 mg All participants were started on LCZ696 100 mg once daily on day 1. For participants who did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 2 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 200 mg. | 8 |
| LCZ696 400 mg All participants were started on LCZ696 100 mg once daily on day 1. For participants who received LCZ696 200 mg and did not achieve msDBP \<80 mmHg and msSBP \<130 mmHg at or after week 4 and had no signs of safety concerns at specified visits during the treatment epoch, the LCZ696 dose was increased to LCZ696 400 mg. | 18 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | LCZ696 100 mg | LCZ696 200 mg | LCZ696 400 mg | Total |
|---|---|---|---|---|
| Age, Continuous | 69.0 Years STANDARD_DEVIATION 5.1 | 71.3 Years STANDARD_DEVIATION 8.8 | 62.3 Years STANDARD_DEVIATION 9.04 | 65.8 Years STANDARD_DEVIATION 9.12 |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants | 8 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 16 Participants | 24 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 | 5 / 32 | 5 / 18 | 9 / 32 | 0 / 26 |
| serious Total, serious adverse events | 0 / 32 | 0 / 18 | 0 / 32 | 0 / 26 |
Outcome results
Primary
Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death)
Percentage of patients with total adverse events, serious adverse events and death were reported.
Time frame: 8 weeks
Population: Safety Set: This set included all participants who received at least one dose of LCZ696. AE analysis was determined by actual treatment, i.e. the LCZ696 dose on the day in which the corresponding summary was targeting. Other safety analysis was determined by the maximum treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LCZ696 100 mg | Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) | Adverse events (serious and non-serious) | 31.3 Percentage of participants |
| LCZ696 100 mg | Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) | Deaths | 0 Percentage of participants |
| LCZ696 100 mg | Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) | Serious Adverse Events | 0 Percentage of participants |
| LCZ696 200 mg | Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) | Adverse events (serious and non-serious) | 0 Percentage of participants |
| LCZ696 200 mg | Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) | Deaths | 0 Percentage of participants |
| LCZ696 200 mg | Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) | Serious Adverse Events | 0 Percentage of participants |
| LCZ696 400 mg | Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) | Serious Adverse Events | 0 Percentage of participants |
| LCZ696 400 mg | Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) | Adverse events (serious and non-serious) | 27.8 Percentage of participants |
| LCZ696 400 mg | Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) | Deaths | 0 Percentage of participants |
| Total LCZ696 | Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) | Adverse events (serious and non-serious) | 43.8 Percentage of participants |
| Total LCZ696 | Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) | Deaths | 0 Percentage of participants |
| Total LCZ696 | Percentage of Participants With Reported Adverse Events (Total Adverse Events, Serious Adverse Events and Death) | Serious Adverse Events | 0 Percentage of participants |
Secondary
Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 8
Time frame: baseline, 8 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LCZ696 100 mg | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 8 | -7.17 mmHg | Standard Deviation 4.69 |
| LCZ696 200 mg | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 8 | -9.94 mmHg | Standard Deviation 7.557 |
| LCZ696 400 mg | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 8 | -7.99 mmHg | Standard Deviation 6.385 |
| Total LCZ696 | Change From Baseline in Mean Sitting Diastolic Blood Pressure (msDBP) at Week 8 | -8.32 mmHg | Standard Deviation 6.308 |
Secondary
Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 8
Sitting BP measurements were performed at screening through the end of study at every visit. Four separate sitting BP were obtained with a full two-minute interval between measurements.
Time frame: baseline, 8 weeks
Population: Full Analysis Set (FAS): This set included all participants who entered the treatment epoch. Patients who were not qualified to enter the treatment epoch were excluded from the FAS provided those participants did not receive LCZ696.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LCZ696 100 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 8 | -19.71 mmHg | Standard Deviation 12.314 |
| LCZ696 200 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 8 | -27.19 mmHg | Standard Deviation 10.557 |
| LCZ696 400 mg | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 8 | -17.79 mmHg | Standard Deviation 10.701 |
| Total LCZ696 | Change From Baseline in Mean Sitting Systolic Blood Pressure (msSBP) at Week 8 | -20.50 mmHg | Standard Deviation 11.329 |
Secondary
Percentage of Participants Achieving a Successful BP Control at Week 8
A successful BP control was defined as msSBP \<130 mmHg and msDBP \<80 mmHg
Time frame: 8 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LCZ696 100 mg | Percentage of Participants Achieving a Successful BP Control at Week 8 | 66.7 Percentage of Participants |
| LCZ696 200 mg | Percentage of Participants Achieving a Successful BP Control at Week 8 | 37.5 Percentage of Participants |
| LCZ696 400 mg | Percentage of Participants Achieving a Successful BP Control at Week 8 | 5.6 Percentage of Participants |
| Total LCZ696 | Percentage of Participants Achieving a Successful BP Control at Week 8 | 25.0 Percentage of Participants |
Secondary
Percentage of Participants Achieving a Successful Response Rate in msDBP at Week 8
Successful response rate was defined as msDBP \<80 mmHg or a reduction of ≥10 mmHg from baseline.
Time frame: 8 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LCZ696 100 mg | Percentage of Participants Achieving a Successful Response Rate in msDBP at Week 8 | 83.3 Percentage of participants |
| LCZ696 200 mg | Percentage of Participants Achieving a Successful Response Rate in msDBP at Week 8 | 87.5 Percentage of participants |
| LCZ696 400 mg | Percentage of Participants Achieving a Successful Response Rate in msDBP at Week 8 | 61.1 Percentage of participants |
| Total LCZ696 | Percentage of Participants Achieving a Successful Response Rate in msDBP at Week 8 | 71.9 Percentage of participants |
Secondary
Percentage of Participants Achieving a Successful Response Rate in msSBP at Week 8
Successful response rate was defined as msSBP \<130 mmHg or a reduction of ≥20 mmHg from baseline
Time frame: 8 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LCZ696 100 mg | Percentage of Participants Achieving a Successful Response Rate in msSBP at Week 8 | 66.7 Percentage of participants |
| LCZ696 200 mg | Percentage of Participants Achieving a Successful Response Rate in msSBP at Week 8 | 75.0 Percentage of participants |
| LCZ696 400 mg | Percentage of Participants Achieving a Successful Response Rate in msSBP at Week 8 | 50.0 Percentage of participants |
| Total LCZ696 | Percentage of Participants Achieving a Successful Response Rate in msSBP at Week 8 | 59.4 Percentage of participants |
Secondary
Percentage of Participants Achieving DBP Control at Week 8
DBP control was defined as msDBP \<80 mmHg.
Time frame: 8 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LCZ696 100 mg | Percentage of Participants Achieving DBP Control at Week 8 | 83.3 Percentage of participants |
| LCZ696 200 mg | Percentage of Participants Achieving DBP Control at Week 8 | 62.5 Percentage of participants |
| LCZ696 400 mg | Percentage of Participants Achieving DBP Control at Week 8 | 27.8 Percentage of participants |
| Total LCZ696 | Percentage of Participants Achieving DBP Control at Week 8 | 46.9 Percentage of participants |
Secondary
Percentage of Participants Achieving SBP Control at Week 8
SBP control was defined as msSBP \<130 mmHg.
Time frame: 8 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LCZ696 100 mg | Percentage of Participants Achieving SBP Control at Week 8 | 66.7 Percentage of participants |
| LCZ696 200 mg | Percentage of Participants Achieving SBP Control at Week 8 | 50.0 Percentage of participants |
| LCZ696 400 mg | Percentage of Participants Achieving SBP Control at Week 8 | 44.4 Percentage of participants |
| Total LCZ696 | Percentage of Participants Achieving SBP Control at Week 8 | 50.0 Percentage of participants |