Trial Outcomes & Findings for Pharmacokinetics of LCZ696 in Subjects With Mild and Moderate Renal Impairment Compared to Healthy Subjects With Normal Renal Function (NCT NCT01569815)
NCT ID: NCT01569815
Last Updated: 2015-10-19
Results Overview
Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
32 participants
Primary outcome timeframe
Day 1 and day 5
Results posted on
2015-10-19
Participant Flow
Participant milestones
| Measure |
Mild Renal Impaired
LCZ696 400 mg once daily for 5 days
|
Mild Renal Impaired Matched Healthy Subjects
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Subjects
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Matched Healthy Subjects
LCZ696 400 mg once daily for 5 days
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
8
|
8
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
8
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics of LCZ696 in Subjects With Mild and Moderate Renal Impairment Compared to Healthy Subjects With Normal Renal Function
Baseline characteristics by cohort
| Measure |
Mild Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Mild Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
51.0 years
STANDARD_DEVIATION 10.88 • n=5 Participants
|
50.6 years
STANDARD_DEVIATION 11.70 • n=7 Participants
|
54.5 years
STANDARD_DEVIATION 8.33 • n=5 Participants
|
53.9 years
STANDARD_DEVIATION 8.95 • n=4 Participants
|
52.5 years
STANDARD_DEVIATION 9.72 • n=21 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
24 Participants
n=21 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
32 Participants
n=21 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: Day 1 and day 5Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Outcome measures
| Measure |
Mild Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Mild Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
|---|---|---|---|---|
|
Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
AHU377 day 1, single dose of LCZ696 400 mg
|
1 hr
Interval 0.5 to 2.0
|
0.5 hr
Interval 0.5 to 1.0
|
0.5 hr
Interval 0.5 to 4.0
|
0.5 hr
Interval 0.0 to 2.0
|
|
Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
AHU377 day 5, multiple doses of LCZ696 400 mg Q.D.
|
1 hr
Interval 0.5 to 2.0
|
0.5 hr
Interval 0.0 to 2.0
|
0.5 hr
Interval 0.5 to 1.0
|
0.5 hr
Interval 0.5 to 1.0
|
|
Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
LBQ657 day 1, single dose of LCZ696 400 mg
|
3 hr
Interval 2.0 to 4.0
|
2 hr
Interval 2.0 to 3.0
|
3 hr
Interval 2.0 to 8.0
|
3 hr
Interval 2.0 to 3.0
|
|
Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
LBQ657 day 5, multiple doses of LCZ696 400 mg Q.D.
|
3 hr
Interval 2.0 to 4.0
|
3 hr
Interval 2.0 to 3.0
|
3 hr
Interval 2.0 to 4.0
|
3 hr
Interval 2.0 to 4.0
|
|
Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
VAL489 day 1, single dose of LCZ696 400 mg
|
2.5 hr
Interval 2.0 to 3.0
|
2 hr
Interval 2.0 to 4.0
|
2 hr
Interval 1.0 to 6.0
|
2 hr
Interval 1.0 to 3.0
|
|
Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
VAL489 day 5,multiple doses LCZ696 400 mg Q.D.
|
2.5 hr
Interval 1.0 to 4.0
|
2 hr
Interval 1.0 to 3.0
|
2 hr
Interval 2.0 to 2.0
|
2 hr
Interval 2.0 to 2.0
|
PRIMARY outcome
Timeframe: Day 1, day 5Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Outcome measures
| Measure |
Mild Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Mild Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
|---|---|---|---|---|
|
Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
AHU377 day 5, multiple doses of LCZ696 400 mg Q.D
|
3904 ng/mL
Standard Deviation 1780
|
3125 ng/mL
Standard Deviation 1729
|
4109 ng/mL
Standard Deviation 1739
|
3756 ng/mL
Standard Deviation 1644
|
|
Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
LBQ657 day 1, single dose of LCZ696 400 mg
|
17575 ng/mL
Standard Deviation 3500
|
15200 ng/mL
Standard Deviation 2958
|
18175 ng/mL
Standard Deviation 3210
|
16000 ng/mL
Standard Deviation 2451
|
|
Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
LBQ657 day 5, multiple doses of LCZ696 400 mg Q.D.
|
27150 ng/mL
Standard Deviation 6449
|
16838 ng/mL
Standard Deviation 3063
|
28988 ng/mL
Standard Deviation 7861
|
18375 ng/mL
Standard Deviation 3215
|
|
Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
VAL489 day 1, single dose of LCZ696 400 mg
|
7208 ng/mL
Standard Deviation 3606
|
6215 ng/mL
Standard Deviation 1588
|
6178 ng/mL
Standard Deviation 2584
|
7981 ng/mL
Standard Deviation 2059
|
|
Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
VAL489 day 5,multiple dose LCZ696 400 mg Q.D.
|
6873 ng/mL
Standard Deviation 4348
|
6275 ng/mL
Standard Deviation 2242
|
7665 ng/mL
Standard Deviation 2612
|
8006 ng/mL
Standard Deviation 3895
|
|
Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
AHU377 day 1, single dose of LCZ696 400 mg
|
4220 ng/mL
Standard Deviation 1514
|
3995 ng/mL
Standard Deviation 1368
|
3539 ng/mL
Standard Deviation 1414
|
3743 ng/mL
Standard Deviation 1486
|
PRIMARY outcome
Timeframe: Day 1 and day 5Population: FAS
Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Outcome measures
| Measure |
Mild Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Mild Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
|---|---|---|---|---|
|
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)
AHU377 day 1, single dose of LCZ696 400 mg
|
5679 ng*hr/mL
Standard Deviation 1864
|
5396 ng*hr/mL
Standard Deviation 1197
|
5359 ng*hr/mL
Standard Deviation 2287
|
5963 ng*hr/mL
Standard Deviation 2559
|
|
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)
AHU377 day 5, multiple doses of LCZ696 400 mg Q.D
|
5656 ng*hr/mL
Standard Deviation 1859
|
5221 ng*hr/mL
Standard Deviation 1162
|
5283 ng*hr/mL
Standard Deviation 2267
|
5716 ng*hr/mL
Standard Deviation 1849
|
|
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)
VAL489 day 5,multiple dose LCZ696 400 mg Q.D
|
59223 ng*hr/mL
Standard Deviation 50669
|
39517 ng*hr/mL
Standard Deviation 17227
|
51777 ng*hr/mL
Standard Deviation 18967
|
56460 ng*hr/mL
Standard Deviation 31412
|
|
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)
LBQ657 day 1, single dose of LCZ696 400 mg
|
226159 ng*hr/mL
Standard Deviation 49810
|
144500 ng*hr/mL
Standard Deviation 15533
|
262422 ng*hr/mL
Standard Deviation 52115
|
154871 ng*hr/mL
Standard Deviation 31504
|
|
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)
LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D.
|
371331 ng*hr/mL
Standard Deviation 99259
|
172335 ng*hr/mL
Standard Deviation 21925
|
437134 ng*hr/mL
Standard Deviation 146930
|
190598 ng*hr/mL
Standard Deviation 44468
|
|
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)
VAL489 day 1, single dose of LCZ696 400 mg
|
62411 ng*hr/mL
Standard Deviation 43846
|
40658 ng*hr/mL
Standard Deviation 11401
|
47135 ng*hr/mL
Standard Deviation 21560
|
50220 ng*hr/mL
Standard Deviation 19732
|
PRIMARY outcome
Timeframe: Day 5Population: FAS
Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Outcome measures
| Measure |
Mild Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Mild Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
|---|---|---|---|---|
|
Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration
AHU377 day 5, multiple doses of LCZ696 400 mg Q.D
|
1.6 hr
Standard Deviation 0.6
|
4.7 hr
Standard Deviation 6.0
|
2.9 hr
Standard Deviation 2.3
|
1.8 hr
Standard Deviation 1.2
|
|
Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration
LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D
|
21.1 hr
Standard Deviation 8.3
|
12.6 hr
Standard Deviation 1.7
|
23.7 hr
Standard Deviation 5.0
|
12.3 hr
Standard Deviation 2.2
|
|
Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration
VAL489 day 5,multiple dose LCZ696 400 mg Q.D
|
15.4 hr
Standard Deviation 4.7
|
14.5 hr
Standard Deviation 3.7
|
22.7 hr
Standard Deviation 14.6
|
12.4 hr
Standard Deviation 3.0
|
PRIMARY outcome
Timeframe: Day 5Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Outcome measures
| Measure |
Mild Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Mild Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
|---|---|---|---|---|
|
Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)
AHU377 day 5, multiple doses of LCZ696 400 mg Q.D
|
38261 mL/hr
Standard Deviation 14002
|
39137 mL/hr
Standard Deviation 10451
|
42704 mL/hr
Standard Deviation 17238
|
37902 mL/hr
Standard Deviation 14487
|
|
Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)
LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D
|
NA mL/hr
Standard Deviation NA
LBQ657 is a metabolite of AHU377, and hence LBQ657 CL/F values are not relevant.
|
NA mL/hr
Standard Deviation NA
LBQ657 is a metabolite of AHU377, and hence LBQ657 CL/F values are not relevant.
|
NA mL/hr
Standard Deviation NA
LBQ657 is a metabolite of AHU377, and hence LBQ657 CL/F values are not relevant.
|
NA mL/hr
Standard Deviation NA
LBQ657 is a metabolite of AHU377, and hence LBQ657 CL/F values are not relevant.
|
|
Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5)
VAL489 day 5,multiple dose LCZ696 400 mg Q.D
|
4636 mL/hr
Standard Deviation 17080
|
6499 mL/hr
Standard Deviation 3876
|
4929 mL/hr
Standard Deviation 3260
|
5988 mL/hr
Standard Deviation 6568
|
PRIMARY outcome
Timeframe: Day 5Population: FAS
Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Outcome measures
| Measure |
Mild Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Mild Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
|---|---|---|---|---|
|
Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)
AHU377 day 5, multiple dose of LCZ696 400 mg Q.D
|
1.0 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)
Standard Deviation 0.1
|
1.0 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)
Standard Deviation 0.2
|
1.0 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)
Standard Deviation 0.2
|
1.0 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)
Standard Deviation 0.2
|
|
Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)
LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D
|
1.64 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)
Standard Deviation 0.27
|
1.19 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)
Standard Deviation 0.09
|
1.6 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)
Standard Deviation 0.3
|
1.2 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)
Standard Deviation 0.1
|
|
Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5)
VAL489 day 5,multiple dose LCZ696 400 mg Q.D
|
1.0 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)
Standard Deviation 0.4
|
0.9 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)
Standard Deviation 0.2
|
1.3 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)
Standard Deviation 0.6
|
1.1 Ratio (AUC0-24, day 5)/(AUC0-24, day 1)
Standard Deviation 0.5
|
PRIMARY outcome
Timeframe: Day 5Population: FAS
Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Outcome measures
| Measure |
Mild Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Mild Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
|---|---|---|---|---|
|
Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)
AHU377 day 5,multiple dose of LCZ696 400 mg Q.D
|
81.2 mL/hr
Standard Deviation 30.5
|
129.1 mL/hr
Standard Deviation 97.0
|
48.9 mL/hr
Standard Deviation 36.3
|
143.9 mL/hr
Standard Deviation 145.2
|
|
Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)
LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D
|
253.1 mL/hr
Standard Deviation 99.0
|
499.0 mL/hr
Standard Deviation 251.3
|
111.0 mL/hr
Standard Deviation 81.4
|
486.0 mL/hr
Standard Deviation 85.7
|
|
Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5)
VAL489 day 5,multiple dose LCZ696 400 mg Q.D
|
141.6 mL/hr
Standard Deviation 84.7
|
313.8 mL/hr
Standard Deviation 144.5
|
73.2 mL/hr
Standard Deviation 43.1
|
317.0 mL/hr
Standard Deviation 109.0
|
PRIMARY outcome
Timeframe: Day 1 and Day 5Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril)
Outcome measures
| Measure |
Mild Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Mild Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
|---|---|---|---|---|
|
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)
LBQ657 day 1, single dose of LCZ696 400 mg
|
52687 ug
Standard Deviation 17107
|
68397 ug
Standard Deviation 17535
|
29653 ug
Standard Deviation 11767
|
75699 ug
Standard Deviation 15612
|
|
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)
VAL489 day 5,multiple dose LCZ696 400 mg Q.D
|
6849 ug
Standard Deviation 3852
|
11625 ug
Standard Deviation 6186
|
3713 ug
Standard Deviation 1843
|
16385 ug
Standard Deviation 8260
|
|
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)
LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D
|
87768 ug
Standard Deviation 21278
|
83254 ug
Standard Deviation 35800
|
43952 ug
Standard Deviation 20678
|
92113 ug
Standard Deviation 22572
|
|
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)
AHU377 day 1, single dose of LCZ696 400 mg
|
360.2 ug
Standard Deviation 99.1
|
1560 ug
Standard Deviation 1294
|
419.4 ug
Standard Deviation 351.1
|
2083 ug
Standard Deviation 2496
|
|
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)
AHU377 day 5, multiple dose of LCZ696 400 mg Q.D
|
426.2 ug
Standard Deviation 120.3
|
734.5 ug
Standard Deviation 662.8
|
316.8 ug
Standard Deviation 362.9
|
790.8 ug
Standard Deviation 872.6
|
|
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)
VAL489 day 1, single dose of LCZ696 400 mg
|
7206 ug
Standard Deviation 3082
|
13792 ug
Standard Deviation 5250
|
4156 ug
Standard Deviation 2634
|
16902 ug
Standard Deviation 4628
|
SECONDARY outcome
Timeframe: From baseline to Day 7Population: FAS
Sodium clearance will be measured in urine from baseline until Day 7
Outcome measures
| Measure |
Mild Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Mild Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
Moderate Renal Impaired Matched Healthy Subjects
n=8 Participants
LCZ696 400 mg once daily for 5 days
|
|---|---|---|---|---|
|
Change in Mean 24-hours Sodium Clearance From Baseline to Day 7
Baseline
|
107.13 mmol/day
Standard Deviation 51.709
|
150.25 mmol/day
Standard Deviation 50.349
|
110.65 mmol/day
Standard Deviation 40.169
|
158.38 mmol/day
Standard Deviation 56.835
|
|
Change in Mean 24-hours Sodium Clearance From Baseline to Day 7
Day 1
|
143.24 mmol/day
Standard Deviation 36.293
|
185.75 mmol/day
Standard Deviation 38.592
|
129.26 mmol/day
Standard Deviation 36.510
|
196.13 mmol/day
Standard Deviation 51.99
|
|
Change in Mean 24-hours Sodium Clearance From Baseline to Day 7
Day 2
|
118.4 mmol/day
Standard Deviation 48.036
|
134.88 mmol/day
Standard Deviation 46.603
|
95.63 mmol/day
Standard Deviation 37.799
|
134.38 mmol/day
Standard Deviation 38.774
|
|
Change in Mean 24-hours Sodium Clearance From Baseline to Day 7
Day 3
|
117.38 mmol/day
Standard Deviation 51.798
|
127.50 mmol/day
Standard Deviation 56.488
|
97.89 mmol/day
Standard Deviation 29.745
|
141.00 mmol/day
Standard Deviation 43.808
|
|
Change in Mean 24-hours Sodium Clearance From Baseline to Day 7
Day 4
|
140.70 mmol/day
Standard Deviation 52.127
|
133.38 mmol/day
Standard Deviation 60.656
|
107.38 mmol/day
Standard Deviation 43.007
|
142.88 mmol/day
Standard Deviation 40.470
|
|
Change in Mean 24-hours Sodium Clearance From Baseline to Day 7
Day 6
|
163.32 mmol/day
Standard Deviation 13.81
|
129.38 mmol/day
Standard Deviation 65.600
|
106.42 mmol/day
Standard Deviation 25.427
|
184.25 mmol/day
Standard Deviation 81.310
|
|
Change in Mean 24-hours Sodium Clearance From Baseline to Day 7
Day 7
|
141.63 mmol/day
Standard Deviation 72.63
|
117.50 mmol/day
Standard Deviation 48.794
|
102.02 mmol/day
Standard Deviation 45.256
|
146.25 mmol/day
Standard Deviation 69.405
|
|
Change in Mean 24-hours Sodium Clearance From Baseline to Day 7
Day 5
|
161.68 mmol/day
Standard Deviation 80.545
|
133.50 mmol/day
Standard Deviation 53.596
|
104.45 mmol/day
Standard Deviation 34.775
|
178.00 mmol/day
Standard Deviation 44.156
|
Adverse Events
LCZ696 400 mg - Mild - Renal Impaired Patients
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
LCZ696 400 mg - Mild - Matched Healthy Subjects
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
LCZ696 400 mg - Moderate - Renal Impaired Patients
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
LCZ696 400 mg - Moderate - Matched Healthy Subjects
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
LCZ696 400 mg - All Healthy Subjects
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
LCZ696 400 mg - Mild - Renal Impaired Patients
n=8 participants at risk
LCZ696 400 mg - Mild - Renal impaired patients
|
LCZ696 400 mg - Mild - Matched Healthy Subjects
n=8 participants at risk
LCZ696 400 mg - Mild - Matched healthy subjects
|
LCZ696 400 mg - Moderate - Renal Impaired Patients
n=8 participants at risk
LCZ696 400 mg - Moderate - Renal impaired patients
|
LCZ696 400 mg - Moderate - Matched Healthy Subjects
n=8 participants at risk
LCZ696 400 mg - Moderate - Matched healthy subjects
|
LCZ696 400 mg - All Healthy Subjects
n=16 participants at risk
LCZ696 400 mg - All healthy subjects
|
|---|---|---|---|---|---|
|
Cardiac disorders
Postural orthostatic tachycardia syndrome
|
25.0%
2/8
|
0.00%
0/8
|
25.0%
2/8
|
0.00%
0/8
|
0.00%
0/16
|
|
Cardiac disorders
Sinus bradycardia
|
12.5%
1/8
|
0.00%
0/8
|
50.0%
4/8
|
0.00%
0/8
|
0.00%
0/16
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/8
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/8
|
6.2%
1/16
|
|
General disorders
Fatigue
|
0.00%
0/8
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/8
|
6.2%
1/16
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/16
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/8
|
0.00%
0/8
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/16
|
|
Nervous system disorders
Somnolence
|
0.00%
0/8
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/8
|
6.2%
1/16
|
|
Renal and urinary disorders
Haematuria
|
12.5%
1/8
|
0.00%
0/8
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/16
|
|
Renal and urinary disorders
Leukocyturia
|
0.00%
0/8
|
0.00%
0/8
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/16
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/8
|
0.00%
0/8
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/16
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/16
|
|
Vascular disorders
Diastolic hypertension
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/16
|
|
Vascular disorders
Hypertension
|
0.00%
0/8
|
0.00%
0/8
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/16
|
|
Vascular disorders
Hypotension
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/8
|
12.5%
1/8
|
6.2%
1/16
|
|
Vascular disorders
Orthostatic hypertension
|
25.0%
2/8
|
0.00%
0/8
|
25.0%
2/8
|
0.00%
0/8
|
0.00%
0/16
|
|
Vascular disorders
Orthostatic hypotension
|
25.0%
2/8
|
25.0%
2/8
|
62.5%
5/8
|
12.5%
1/8
|
18.8%
3/16
|
Additional Information
Study Director
Novartis Pharmaceuticals
Phone: 862-778-8300
Results disclosure agreements
- Principal investigator is a sponsor employee 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
- Publication restrictions are in place
Restriction type: OTHER