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This study assessed the safety, tolerability, and efficacy of LCZ696 in severe hypertensive Japanese patients
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LCZ696 200 mg | Experimental | 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. |
|
| LCZ696 400 mg | Experimental | 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. |
|
| LCZ696 400 mg plus other hypertension (HTN) medications | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LCZ696 | Drug | LCZ696 200 mg tablet once daily |
| |
| LCZ696 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Week 8 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
Other protocol defined inclusion/exclusion criteria may apply.
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Yokohama | Kanagawa | 231-0023 | Japan | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26402918 | Result | Kario K, Tamaki Y, Okino N, Gotou H, Zhu M, Zhang J. LCZ696, a First-in-Class Angiotensin Receptor-Neprilysin Inhibitor: The First Clinical Experience in Patients With Severe Hypertension. J Clin Hypertens (Greenwich). 2016 Apr;18(4):308-14. doi: 10.1111/jch.12667. Epub 2015 Sep 24. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Treatment Assignment Set (TRTAG): This set included all patients who entered the treatment epoch.
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | 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. | Posted | Number | Percentage of participants | Week 8 |
|
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SAE and other AE analyses were 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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | LCZ 200 mg | LCZ 200 mg |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ALANINE AMINOTRANSFERASE INCREASED | Investigations | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| NASOPHARYNGITIS | Infections and infestations | MedDRA | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | +1-862-778-8300 |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C549068 | sacubitril and valsartan sodium hydrate drug combination |
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| Drug |
2 tablets of LCZ696 200 mg once daily titrated up from 1 tablet of 200 mg once daily |
|
| LCZ696 | Drug | 2 tablets of LCZ696 200 mg once daily titrated up from 1 tablet of 200 mg once daily plus other HTN medications |
|
| Baseline, 8 weeks |
| 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. | 8 weeks |
| 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. | 8 weeks |
| 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. | 8 weeks |
| Percentage of Participants With SBP Response at End of Study | SBP response was defined as <140 mmHg or a reduction ≥ 20 mmHg from baseline. | Baseline, 8 weeks |
| Percentage of Participants With DBP Response at End of Study | DBP response was defined as <90 mmHg or a reduction ≥ 10 mmHg from baseline. | Baseline, 8 weeks |
| Kyoto |
| Kyoto |
| 606-8507 |
| Japan |
| Novartis Investigative Site | Bunkyo-ku | Tokyo | 113-0031 | Japan |
| Novartis Investigative Site | Hachiōji | Tokyo | 192-0918 | Japan |
| Novartis Investigative Site | Minato-ku | Tokyo | 105-7390 | Japan |
| Novartis Investigative Site | Minato-ku | Tokyo | 108-0075 | Japan |
| Novartis Investigative Site | Ōta-ku | Tokyo | 143-0023 | Japan |
| Novartis Investigative Site | Shibuya-ku | Tokyo | 150-0002 | Japan |
| Novartis Investigative Site | Shinagawa-ku | Tokyo | 141-0032 | Japan |
| BG001 | 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. |
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | 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. |
| OG002 | 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. |
| OG003 | Total Participants | All participants who were treated |
|
|
| 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. | 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. | Posted | Mean | Standard Deviation | mmHg | Baseline, 8 weeks |
|
|
|
| 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. | 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. | Posted | Number | Percentage of Participants | 8 weeks |
|
|
|
| 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. | 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. | Posted | Number | Percentage of Participants | 8 weeks |
|
|
|
| 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. | 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. | Posted | Number | Percentage of Participants | 8 weeks |
|
|
|
| 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. | 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. | Posted | Number | Percentage of Participants | Baseline, 8 weeks |
|
|
|
| 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. | 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. | Posted | Number | Percentage of Participants | Baseline, 8 weeks |
|
|
|
| 1 |
| 35 |
| 4 |
| 35 |
| EG001 | LCZ 400 mg | LCZ 400 mg | 0 | 32 | 2 | 32 |
| EG002 | LCZ 400 mg + Other HTN Medications | LCZ 400 mg + other HTN medications | 0 | 21 | 5 | 21 |
| EG003 | Total Participants | All participants who were treated | 1 | 35 | 10 | 35 |
| ASPARTATE AMINOTRANSFERASE INCREASED | Investigations | MedDRA | Systematic Assessment |
|
| BLOOD CREATINE PHOSPHOKINASE INCREASED | Investigations | MedDRA | Systematic Assessment |
|
| HYPERURICAEMIA | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
| msDBP |
|