Pharmacokinetics of LCZ696 in Subjects With Mild and Moderate Renal Impairment Compared to Healthy Subjects With Normal Renal Function
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01569815
Collaborator
(none)
32
3
1
65.9
10.7
0.2
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
32 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Basic Science
Official Title:
An Open Label, Parallel-group Study to Determine Multiple Dose Pharmacokinetics of LCZ696 and Its Metabolites in Subjects With Mild and Moderate Renal Impairment Compared to Matched Healthy Subjects With Normal Renal Function
Study Start Date
:
Feb 1, 2009
Actual Primary Completion Date
:
Aug 1, 2014
Actual Study Completion Date
:
Aug 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: LCZ696 400 mg LCZ696 400 mg once daily for 5 days |
Drug: LCZ696
LCZ696 400 mg once daily
|
Outcome Measures
Primary Outcome Measures
- Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5) [Day 1 and 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)
- Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5) [Day 1, 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)
- 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) [Day 1 and 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)
- Elimination Half-life (t1/2) After Multiple Dose (Day 5) 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)
- Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5) [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)
- Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5) [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)
- Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5) [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)
- 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) [Day 1 and 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)
Secondary Outcome Measures
- Change in Mean 24-hours Sodium Clearance From Baseline to Day 7 [From baseline to Day 7]
Sodium clearance will be measured in urine from baseline until Day 7
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Male, and female subjects of non-child bearing potential,
-
Subjects were to weigh at least 50 kg to participate in the study,
-
and body mass index < 40 kg/m2
-
Subjects were able to communicate well with the investigator, to understand and comply with the requirements of the study;
-
Subjects were able to understand and sign the written informed consent;
For renal insufficient subjects:
- stable renal disease without evidence of renal progressive
-
mild renal function: calculated CrCl of 50-≤80 mL/min
-
moderate renal function: calculated CrCl of 30-<50 mL/min
- Vital signs:
-
oral body temperature between 35.0-37.8 °C
-
systolic blood pressure, 95-180 mm Hg
-
diastolic blood pressure, 60-110 mm Hg
-
pulse rate, 54-95 bpm
For healthy subjects only
-
A serum creatinine with a calculated CrCl of >80 mL/min
-
Vital signs:
-
oral body temperature between 35.0-37.2 °C
-
systolic blood pressure, 95-140 mm Hg
-
diastolic blood pressure, 60-100 mm Hg
-
pulse rate, 45-90 bpm
Exclusion Criteria:
-
Current use of ACE inhibitors, valsartan, and drugs that were known as CYP2C9 substrates, potassium-sparing diuretics;
-
Smokers;
-
History of renal transplant at any time in the past and on immunosuppressant therapy;
-
Dialysis patients;
-
Medical history of clinically significant ECG abnormalities or a family history of a prolonged QT-interval syndrome;
-
Any surgical or medical condition which may significantly alter the absorption, distribution, metabolism or excretion of any drug substance; Other protocol defined inclusion/exclusion criteria may apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Neuss | Germany | 41460 | |
| 2 | Novartis Investigative Site | Moscow | Russian Federation | 117292 | |
| 3 | Novartis Investigative Site | Belgrade | Serbia |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01569815
Other Study ID Numbers:
- CLCZ696A2204
- 2007-005480-96
First Posted:
Apr 3, 2012
Last Update Posted:
Oct 19, 2015
Last Verified:
Sep 1, 2015
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Mild Renal Impaired | Mild Renal Impaired Matched Healthy Subjects | Moderate Renal Impaired Subjects | Moderate Renal Impaired Matched Healthy Subjects |
|---|---|---|---|---|
| Arm/Group Description | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days |
| Period Title: Overall Study | ||||
| STARTED | 8 | 8 | 8 | 8 |
| COMPLETED | 8 | 8 | 8 | 8 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Mild Renal Impaired Subjects | Mild Renal Impaired Matched Healthy Subjects | Moderate Renal Impaired Subjects | Moderate Renal Impaired Matched Healthy Subjects | Total |
|---|---|---|---|---|---|
| Arm/Group Description | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | Total of all reporting groups |
| Overall Participants | 8 | 8 | 8 | 8 | 32 |
| Age (years) [Mean (Standard Deviation) ] | |||||
| Mean (Standard Deviation) [years] |
51.0
(10.88)
|
50.6
(11.70)
|
54.5
(8.33)
|
53.9
(8.95)
|
52.5
(9.72)
|
| Sex: Female, Male (Count of Participants) | |||||
| Female |
1
12.5%
|
1
12.5%
|
3
37.5%
|
3
37.5%
|
8
25%
|
| Male |
7
87.5%
|
7
87.5%
|
5
62.5%
|
5
62.5%
|
24
75%
|
| Race (NIH/OMB) (Count of Participants) | |||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
8
100%
|
8
100%
|
8
100%
|
8
100%
|
32
100%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5) |
|---|---|
| Description | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) |
| Time Frame | Day 1 and day 5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Mild Renal Impaired Subjects | Mild Renal Impaired Matched Healthy Subjects | Moderate Renal Impaired Subjects | Moderate Renal Impaired Matched Healthy Subjects |
|---|---|---|---|---|
| Arm/Group Description | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days |
| Measure Participants | 8 | 8 | 8 | 8 |
| AHU377 day 1, single dose of LCZ696 400 mg |
1
|
0.5
|
0.5
|
0.5
|
| AHU377 day 5, multiple doses of LCZ696 400 mg Q.D. |
1
|
0.5
|
0.5
|
0.5
|
| LBQ657 day 1, single dose of LCZ696 400 mg |
3
|
2
|
3
|
3
|
| LBQ657 day 5, multiple doses of LCZ696 400 mg Q.D. |
3
|
3
|
3
|
3
|
| VAL489 day 1, single dose of LCZ696 400 mg |
2.5
|
2
|
2
|
2
|
| VAL489 day 5,multiple doses LCZ696 400 mg Q.D. |
2.5
|
2
|
2
|
2
|
| Title | Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5) |
|---|---|
| Description | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) |
| Time Frame | Day 1, day 5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Mild Renal Impaired Subjects | Mild Renal Impaired Matched Healthy Subjects | Moderate Renal Impaired Subjects | Moderate Renal Impaired Matched Healthy Subjects |
|---|---|---|---|---|
| Arm/Group Description | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days |
| Measure Participants | 8 | 8 | 8 | 8 |
| AHU377 day 1, single dose of LCZ696 400 mg |
4220
(1514)
|
3995
(1368)
|
3539
(1414)
|
3743
(1486)
|
| AHU377 day 5, multiple doses of LCZ696 400 mg Q.D |
3904
(1780)
|
3125
(1729)
|
4109
(1739)
|
3756
(1644)
|
| LBQ657 day 1, single dose of LCZ696 400 mg |
17575
(3500)
|
15200
(2958)
|
18175
(3210)
|
16000
(2451)
|
| LBQ657 day 5, multiple doses of LCZ696 400 mg Q.D. |
27150
(6449)
|
16838
(3063)
|
28988
(7861)
|
18375
(3215)
|
| VAL489 day 1, single dose of LCZ696 400 mg |
7208
(3606)
|
6215
(1588)
|
6178
(2584)
|
7981
(2059)
|
| VAL489 day 5,multiple dose LCZ696 400 mg Q.D. |
6873
(4348)
|
6275
(2242)
|
7665
(2612)
|
8006
(3895)
|
| Title | 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) |
|---|---|
| Description | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) |
| Time Frame | Day 1 and day 5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | Mild Renal Impaired Subjects | Mild Renal Impaired Matched Healthy Subjects | Moderate Renal Impaired Subjects | Moderate Renal Impaired Matched Healthy Subjects |
|---|---|---|---|---|
| Arm/Group Description | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days |
| Measure Participants | 8 | 8 | 8 | 8 |
| AHU377 day 1, single dose of LCZ696 400 mg |
5679
(1864)
|
5396
(1197)
|
5359
(2287)
|
5963
(2559)
|
| AHU377 day 5, multiple doses of LCZ696 400 mg Q.D |
5656
(1859)
|
5221
(1162)
|
5283
(2267)
|
5716
(1849)
|
| LBQ657 day 1, single dose of LCZ696 400 mg |
226159
(49810)
|
144500
(15533)
|
262422
(52115)
|
154871
(31504)
|
| LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D. |
371331
(99259)
|
172335
(21925)
|
437134
(146930)
|
190598
(44468)
|
| VAL489 day 1, single dose of LCZ696 400 mg |
62411
(43846)
|
40658
(11401)
|
47135
(21560)
|
50220
(19732)
|
| VAL489 day 5,multiple dose LCZ696 400 mg Q.D |
59223
(50669)
|
39517
(17227)
|
51777
(18967)
|
56460
(31412)
|
| Title | Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration |
|---|---|
| Description | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) |
| Time Frame | Day 5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | Mild Renal Impaired Subjects | Mild Renal Impaired Matched Healthy Subjects | Moderate Renal Impaired Subjects | Moderate Renal Impaired Matched Healthy Subjects |
|---|---|---|---|---|
| Arm/Group Description | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days |
| Measure Participants | 8 | 8 | 8 | 8 |
| AHU377 day 5, multiple doses of LCZ696 400 mg Q.D |
1.6
(0.6)
|
4.7
(6.0)
|
2.9
(2.3)
|
1.8
(1.2)
|
| LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D |
21.1
(8.3)
|
12.6
(1.7)
|
23.7
(5.0)
|
12.3
(2.2)
|
| VAL489 day 5,multiple dose LCZ696 400 mg Q.D |
15.4
(4.7)
|
14.5
(3.7)
|
22.7
(14.6)
|
12.4
(3.0)
|
| Title | Systemic Clearance From Plasma Following Extravascular Administration (CL/F) After Multiple Dose Administration (Day 5) |
|---|---|
| Description | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) |
| Time Frame | Day 5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Mild Renal Impaired Subjects | Mild Renal Impaired Matched Healthy Subjects | Moderate Renal Impaired Subjects | Moderate Renal Impaired Matched Healthy Subjects |
|---|---|---|---|---|
| Arm/Group Description | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days |
| Measure Participants | 8 | 8 | 8 | 8 |
| AHU377 day 5, multiple doses of LCZ696 400 mg Q.D |
38261
(14002)
|
39137
(10451)
|
42704
(17238)
|
37902
(14487)
|
| LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
| VAL489 day 5,multiple dose LCZ696 400 mg Q.D |
4636
(17080)
|
6499
(3876)
|
4929
(3260)
|
5988
(6568)
|
| Title | Accumulation Ratio (Racc) After Multiple Dose Administration (Day 5) |
|---|---|
| Description | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) |
| Time Frame | Day 5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | Mild Renal Impaired Subjects | Mild Renal Impaired Matched Healthy Subjects | Moderate Renal Impaired Subjects | Moderate Renal Impaired Matched Healthy Subjects |
|---|---|---|---|---|
| Arm/Group Description | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days |
| Measure Participants | 8 | 8 | 8 | 8 |
| AHU377 day 5, multiple dose of LCZ696 400 mg Q.D |
1.0
(0.1)
|
1.0
(0.2)
|
1.0
(0.2)
|
1.0
(0.2)
|
| LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D |
1.64
(0.27)
|
1.19
(0.09)
|
1.6
(0.3)
|
1.2
(0.1)
|
| VAL489 day 5,multiple dose LCZ696 400 mg Q.D |
1.0
(0.4)
|
0.9
(0.2)
|
1.3
(0.6)
|
1.1
(0.5)
|
| Title | Renal Clearance From Plasma (CLr) After Multiple Dose Administration (Day 5) |
|---|---|
| Description | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) |
| Time Frame | Day 5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | Mild Renal Impaired Subjects | Mild Renal Impaired Matched Healthy Subjects | Moderate Renal Impaired Subjects | Moderate Renal Impaired Matched Healthy Subjects |
|---|---|---|---|---|
| Arm/Group Description | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days |
| Measure Participants | 8 | 8 | 8 | 8 |
| AHU377 day 5,multiple dose of LCZ696 400 mg Q.D |
81.2
(30.5)
|
129.1
(97.0)
|
48.9
(36.3)
|
143.9
(145.2)
|
| LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D |
253.1
(99.0)
|
499.0
(251.3)
|
111.0
(81.4)
|
486.0
(85.7)
|
| VAL489 day 5,multiple dose LCZ696 400 mg Q.D |
141.6
(84.7)
|
313.8
(144.5)
|
73.2
(43.1)
|
317.0
(109.0)
|
| Title | 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) |
|---|---|
| Description | Blood samples will be collected for the determination of plasma concentrations of VAL489 (valsartan), AHU377( Sacubitril) and LBQ657 (a human metabolite of sacubitril) |
| Time Frame | Day 1 and Day 5 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Mild Renal Impaired Subjects | Mild Renal Impaired Matched Healthy Subjects | Moderate Renal Impaired Subjects | Moderate Renal Impaired Matched Healthy Subjects |
|---|---|---|---|---|
| Arm/Group Description | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days |
| Measure Participants | 8 | 8 | 8 | 8 |
| AHU377 day 1, single dose of LCZ696 400 mg |
360.2
(99.1)
|
1560
(1294)
|
419.4
(351.1)
|
2083
(2496)
|
| AHU377 day 5, multiple dose of LCZ696 400 mg Q.D |
426.2
(120.3)
|
734.5
(662.8)
|
316.8
(362.9)
|
790.8
(872.6)
|
| LBQ657 day 1, single dose of LCZ696 400 mg |
52687
(17107)
|
68397
(17535)
|
29653
(11767)
|
75699
(15612)
|
| LBQ657 day 5, multiple dose of LCZ696 400 mg Q.D |
87768
(21278)
|
83254
(35800)
|
43952
(20678)
|
92113
(22572)
|
| VAL489 day 1, single dose of LCZ696 400 mg |
7206
(3082)
|
13792
(5250)
|
4156
(2634)
|
16902
(4628)
|
| VAL489 day 5,multiple dose LCZ696 400 mg Q.D |
6849
(3852)
|
11625
(6186)
|
3713
(1843)
|
16385
(8260)
|
| Title | Change in Mean 24-hours Sodium Clearance From Baseline to Day 7 |
|---|---|
| Description | Sodium clearance will be measured in urine from baseline until Day 7 |
| Time Frame | From baseline to Day 7 |
Outcome Measure Data
| Analysis Population Description |
|---|
| FAS |
| Arm/Group Title | Mild Renal Impaired Subjects | Mild Renal Impaired Matched Healthy Subjects | Moderate Renal Impaired Subjects | Moderate Renal Impaired Matched Healthy Subjects |
|---|---|---|---|---|
| Arm/Group Description | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days | LCZ696 400 mg once daily for 5 days |
| Measure Participants | 8 | 8 | 8 | 8 |
| Baseline |
107.13
(51.709)
|
150.25
(50.349)
|
110.65
(40.169)
|
158.38
(56.835)
|
| Day 1 |
143.24
(36.293)
|
185.75
(38.592)
|
129.26
(36.510)
|
196.13
(51.99)
|
| Day 2 |
118.4
(48.036)
|
134.88
(46.603)
|
95.63
(37.799)
|
134.38
(38.774)
|
| Day 3 |
117.38
(51.798)
|
127.50
(56.488)
|
97.89
(29.745)
|
141.00
(43.808)
|
| Day 4 |
140.70
(52.127)
|
133.38
(60.656)
|
107.38
(43.007)
|
142.88
(40.470)
|
| Day 5 |
161.68
(80.545)
|
133.50
(53.596)
|
104.45
(34.775)
|
178.00
(44.156)
|
| Day 6 |
163.32
(13.81)
|
129.38
(65.600)
|
106.42
(25.427)
|
184.25
(81.310)
|
| Day 7 |
141.63
(72.63)
|
117.50
(48.794)
|
102.02
(45.256)
|
146.25
(69.405)
|
Adverse Events
| Time Frame | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | LCZ696 400 mg - Mild - Renal Impaired Patients | LCZ696 400 mg - Mild - Matched Healthy Subjects | LCZ696 400 mg - Moderate - Renal Impaired Patients | LCZ696 400 mg - Moderate - Matched Healthy Subjects | LCZ696 400 mg - All Healthy Subjects | |||||
| Arm/Group Description | LCZ696 400 mg - Mild - Renal impaired patients | LCZ696 400 mg - Mild - Matched healthy subjects | LCZ696 400 mg - Moderate - Renal impaired patients | LCZ696 400 mg - Moderate - Matched healthy subjects | LCZ696 400 mg - All healthy subjects | |||||
All Cause Mortality |
||||||||||
| LCZ696 400 mg - Mild - Renal Impaired Patients | LCZ696 400 mg - Mild - Matched Healthy Subjects | LCZ696 400 mg - Moderate - Renal Impaired Patients | LCZ696 400 mg - Moderate - Matched Healthy Subjects | LCZ696 400 mg - All Healthy Subjects | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||
Serious Adverse Events |
||||||||||
| LCZ696 400 mg - Mild - Renal Impaired Patients | LCZ696 400 mg - Mild - Matched Healthy Subjects | LCZ696 400 mg - Moderate - Renal Impaired Patients | LCZ696 400 mg - Moderate - Matched Healthy Subjects | LCZ696 400 mg - All Healthy Subjects | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/16 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| LCZ696 400 mg - Mild - Renal Impaired Patients | LCZ696 400 mg - Mild - Matched Healthy Subjects | LCZ696 400 mg - Moderate - Renal Impaired Patients | LCZ696 400 mg - Moderate - Matched Healthy Subjects | LCZ696 400 mg - All Healthy Subjects | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/8 (87.5%) | 3/8 (37.5%) | 8/8 (100%) | 1/8 (12.5%) | 4/16 (25%) | |||||
| Cardiac disorders | ||||||||||
| Postural orthostatic tachycardia syndrome | 2/8 (25%) | 0/8 (0%) | 2/8 (25%) | 0/8 (0%) | 0/16 (0%) | |||||
| Sinus bradycardia | 1/8 (12.5%) | 0/8 (0%) | 4/8 (50%) | 0/8 (0%) | 0/16 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Diarrhoea | 0/8 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/8 (0%) | 1/16 (6.3%) | |||||
| General disorders | ||||||||||
| Fatigue | 0/8 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/8 (0%) | 1/16 (6.3%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Hyperkalaemia | 1/8 (12.5%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/16 (0%) | |||||
| Hyperuricaemia | 0/8 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/16 (0%) | |||||
| Nervous system disorders | ||||||||||
| Somnolence | 0/8 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/8 (0%) | 1/16 (6.3%) | |||||
| Renal and urinary disorders | ||||||||||
| Haematuria | 1/8 (12.5%) | 0/8 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/16 (0%) | |||||
| Leukocyturia | 0/8 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/16 (0%) | |||||
| Renal impairment | 0/8 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/16 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Pruritus | 1/8 (12.5%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/16 (0%) | |||||
| Vascular disorders | ||||||||||
| Diastolic hypertension | 1/8 (12.5%) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) | 0/16 (0%) | |||||
| Hypertension | 0/8 (0%) | 0/8 (0%) | 1/8 (12.5%) | 0/8 (0%) | 0/16 (0%) | |||||
| Hypotension | 1/8 (12.5%) | 0/8 (0%) | 0/8 (0%) | 1/8 (12.5%) | 1/16 (6.3%) | |||||
| Orthostatic hypertension | 2/8 (25%) | 0/8 (0%) | 2/8 (25%) | 0/8 (0%) | 0/16 (0%) | |||||
| Orthostatic hypotension | 2/8 (25%) | 2/8 (25%) | 5/8 (62.5%) | 1/8 (12.5%) | 3/16 (18.8%) | |||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis Pharmaceuticals |
| Phone | 862-778-8300 |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01569815
Other Study ID Numbers:
- CLCZ696A2204
- 2007-005480-96
First Posted:
Apr 3, 2012
Last Update Posted:
Oct 19, 2015
Last Verified:
Sep 1, 2015