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| ID | Type | Description | Link |
|---|---|---|---|
| 2007-005480-96 | EudraCT Number |
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The purpose of this study is to determine the multiple dose pharmacokinetics of LCZ696 and its metabolites in subjects with mild to moderate renal impairment and to evaluate the safety of LCZ696 in this population.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| LCZ696 400 mg | Experimental | LCZ696 400 mg once daily for 5 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| LCZ696 | Drug | LCZ696 400 mg once daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 1 and day 5 |
| Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 1, day 5 |
| Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 1 and day 5 |
| Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 5 |
| Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 5 |
| Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Mean 24-hours Sodium Clearance From Baseline to Day 7 | Sodium clearance will be measured in urine from baseline until Day 7 | From baseline to Day 7 |
Not provided
Inclusion Criteria:
For renal insufficient subjects:
stable renal disease without evidence of renal progressive
Vital signs:
For healthy subjects only
A serum creatinine with a calculated CrCl of >80 mL/min
Vital signs:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Neuss | 41460 | Germany | |||
| Novartis Investigative Site |
Not provided
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| ID | Title | Description |
|---|---|---|
| FG000 | Mild Renal Impaired | LCZ696 400 mg once daily for 5 days |
| FG001 | Mild Renal Impaired Matched Healthy Subjects | LCZ696 400 mg once daily for 5 days |
| FG002 | Moderate Renal Impaired Subjects | LCZ696 400 mg once daily for 5 days |
| FG003 | Moderate Renal Impaired Matched Healthy Subjects | LCZ696 400 mg once daily for 5 days |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
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| ID | Title | Description |
|---|---|---|
| BG000 | Mild Renal Impaired Subjects | LCZ696 400 mg once daily for 5 days |
| BG001 | Mild Renal Impaired Matched Healthy Subjects | LCZ696 400 mg once daily for 5 days |
| 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 | Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Posted | Median | Full Range | hr | Day 1 and day 5 |
|
Not provided
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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 | LCZ696 400 mg - Mild - Renal Impaired Patients | LCZ696 400 mg - Mild - Renal impaired patients |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Postural orthostatic tachycardia syndrome | Cardiac disorders | MedDRA | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862-778-8300 |
Not provided
| ID | Term |
|---|---|
| D008224 | Lymphoma, Follicular |
| D051437 | Renal Insufficiency |
| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
Not provided
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| ID | Term |
|---|---|
| C549068 | sacubitril and valsartan sodium hydrate drug combination |
Not provided
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Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) |
| Day 5 |
| Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 5 |
| Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Day 1 and Day 5 |
| Moscow |
| 117292 |
| Russia |
| Novartis Investigative Site | Belgrade | Serbia |
| BG002 | Moderate Renal Impaired Subjects | LCZ696 400 mg once daily for 5 days |
| BG003 | Moderate Renal Impaired Matched Healthy Subjects | LCZ696 400 mg once daily for 5 days |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
LCZ696 400 mg once daily for 5 days |
| OG003 | Moderate Renal Impaired Matched Healthy Subjects | LCZ696 400 mg once daily for 5 days |
|
|
| Primary | Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Posted | Mean | Standard Deviation | ng/mL | Day 1, day 5 |
|
|
|
| Primary | Area Under the Concentration-time Curve (AUC0-24) From Time Zero to 24- Hour Post-dose (Day 1), and After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | FAS | Posted | Mean | Standard Deviation | ng*hr/mL | Day 1 and day 5 |
|
|
|
| Primary | Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | FAS | Posted | Mean | Standard Deviation | hr | Day 5 |
|
|
|
| Primary | Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Posted | Mean | Standard Deviation | mL/hr | Day 5 |
|
|
|
| Primary | Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | FAS | Posted | Mean | Standard Deviation | Ratio (AUC0-24, day 5)/(AUC0-24, day 1) | Day 5 |
|
|
|
| Primary | Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | FAS | Posted | Mean | Standard Deviation | mL/hr | Day 5 |
|
|
|
| Primary | Amount of Drug Excreted Into the Urine From Time Zero to 24-hours Post-dose (Ae0-24) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5) | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) | Posted | Mean | Standard Deviation | ug | Day 1 and Day 5 |
|
|
|
| Secondary | Change in Mean 24-hours Sodium Clearance From Baseline to Day 7 | Sodium clearance will be measured in urine from baseline until Day 7 | FAS | Posted | Mean | Standard Deviation | mmol/day | From baseline to Day 7 |
|
|
|
| 0 |
| 8 |
| 7 |
| 8 |
| EG001 | LCZ696 400 mg - Mild - Matched Healthy Subjects | LCZ696 400 mg - Mild - Matched healthy subjects | 0 | 8 | 3 | 8 |
| EG002 | LCZ696 400 mg - Moderate - Renal Impaired Patients | LCZ696 400 mg - Moderate - Renal impaired patients | 0 | 8 | 8 | 8 |
| EG003 | LCZ696 400 mg - Moderate - Matched Healthy Subjects | LCZ696 400 mg - Moderate - Matched healthy subjects | 0 | 8 | 1 | 8 |
| EG004 | LCZ696 400 mg - All Healthy Subjects | LCZ696 400 mg - All healthy subjects | 0 | 16 | 4 | 16 |
| Sinus bradycardia | Cardiac disorders | MedDRA | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Leukocyturia | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | MedDRA | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Diastolic hypertension | Vascular disorders | MedDRA | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA | Systematic Assessment |
|
| Hypotension | Vascular disorders | MedDRA | Systematic Assessment |
|
| Orthostatic hypertension | Vascular disorders | MedDRA | Systematic Assessment |
|
| Orthostatic hypotension | Vascular 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 (ie, data from all sites) in the clinical trial
| D008232 |
| Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| AHU377 day 5, multiple doses of LCZ696 400 mg Q.D |
|
| LBQ657 day 1, single dose of LCZ696 400 mg |
|
| LBQ657 day 5, multiple doses of LCZ696 400 mg Q.D. |
|
| VAL489 day 1, single dose of LCZ696 400 mg |
|
| VAL489 day 5,multiple dose LCZ696 400 mg Q.D. |
|
| AHU377 day 5, multiple doses of LCZ696 400 mg Q.D |
|
| LBQ657 day 1, single dose of LCZ696 400 mg |
|
| LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D. |
|
| VAL489 day 1, single dose of LCZ696 400 mg |
|
| VAL489 day 5,multiple dose LCZ696 400 mg Q.D |
|
| LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D |
|
| VAL489 day 5,multiple dose LCZ696 400 mg Q.D |
|
| LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D |
|
| VAL489 day 5,multiple dose LCZ696 400 mg Q.D |
|
| LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D |
|
| VAL489 day 5,multiple dose LCZ696 400 mg Q.D |
|
| LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D |
|
| VAL489 day 5,multiple dose LCZ696 400 mg Q.D |
|
| AHU377 day 5, multiple dose of LCZ696 400 mg Q.D |
|
| LBQ657 day 1, single dose of LCZ696 400 mg |
|
| LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D |
|
| VAL489 day 1, single dose of LCZ696 400 mg |
|
| VAL489 day 5,multiple dose LCZ696 400 mg Q.D |
|
| Day 1 |
|
| Day 2 |
|
| Day 3 |
|
| Day 4 |
|
| Day 5 |
|
| Day 6 |
|
| Day 7 |
|