Trial Outcomes & Findings for A Study of LCZ696 in Subjects With Mild and Moderate Hepatic Impairment Compared With Normal Healthy Volunteers (NCT NCT01621633)
NCT ID: NCT01621633
Last Updated: 2015-08-10
Results Overview
Blood samples were taken on Day 1 (treatment day) within 60 minutes prior to dosing, then, 0.5,1,1.5,2,3,4,6,8,12 hours after the dosing and on Days 2, 3, 4 and 5 post dosing
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
32 participants
Primary outcome timeframe
From pre-dose on Day 1 until 96h post-dose (Day 5)
Results posted on
2015-08-10
Participant Flow
Participants received the study treatment according to the population subset that was defined based on the severity of hepatic impairment and healthy volunteers: Group 1, subjects with mild hepatic impairment; Group 2, subjects with moderate hepatic impairment; Groups 3 and 4, healthy volunteers matching to Groups 1 and 2, respectively.
Participant milestones
| Measure |
Participants With Mild Hepatic Impairment (HI)
LCZ696 200 mg, given as a single oral dose
|
Participants With Moderate Hepatic Impairment (HI)
LCZ696 200 mg, given as a single oral dose
|
Healthy Volunteers (Mild HI Matched)
LCZ696 200 mg, given as a single oral dose. Each healthy volunteer matched in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in group 1
|
Healthy Volunteers (Moderate HI Matched)
LCZ696 200 mg, given as a single oral dose. Each healthy volunteer matched in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in group 2
|
|---|---|---|---|---|
|
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
A Study of LCZ696 in Subjects With Mild and Moderate Hepatic Impairment Compared With Normal Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Participants With Mild Hepatic Impairment (HI)
n=8 Participants
LCZ696 200 mg, given as a single oral dose
|
Participants With Moderate Hepatic Impairment (HI)
n=8 Participants
LCZ696 200 mg, given as a single oral dose
|
Healthy Volunteers (Mild HI Matched)
n=8 Participants
LCZ696 200 mg, given as a single oral dose. Each healthy volunteer matched in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in group 1
|
Healthy Volunteers (Moderate HI Matched)
n=8 Participants
LCZ696 200 mg, given as a single oral dose. Each healthy volunteer matched in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in group 2
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
59.1 Years
STANDARD_DEVIATION 7.92 • n=93 Participants
|
57.9 Years
STANDARD_DEVIATION 11.67 • n=4 Participants
|
58.9 Years
STANDARD_DEVIATION 8.68 • n=27 Participants
|
60.3 Years
STANDARD_DEVIATION 11.21 • n=483 Participants
|
59.0 Years
STANDARD_DEVIATION 9.54 • n=36 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
3 Participants
n=27 Participants
|
1 Participants
n=483 Participants
|
8 Participants
n=36 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
7 Participants
n=483 Participants
|
24 Participants
n=36 Participants
|
PRIMARY outcome
Timeframe: From pre-dose on Day 1 until 96h post-dose (Day 5)Population: PK analysis set: The PK analysis set included all subjects with at least one available, valid (i.e. not flagged for exclusion) PK concentration measurement, who received any study drug, and experienced no protocol deviations with relevant impact on PK data.
Blood samples were taken on Day 1 (treatment day) within 60 minutes prior to dosing, then, 0.5,1,1.5,2,3,4,6,8,12 hours after the dosing and on Days 2, 3, 4 and 5 post dosing
Outcome measures
| Measure |
Participants With Mild Hepatic Impairment (HI)
n=8 Participants
LCZ696 200 mg, given as a single oral dose
|
Participants With Moderate Hepatic Impairment (HI)
n=8 Participants
LCZ696 200 mg, given as a single oral dose
|
Healthy Volunteers (Mild HI Matched)
n=8 Participants
LCZ696 200 mg, given as a single oral dose. Each healthy volunteer matched in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in group 1
|
Healthy Volunteers (Moderate HI Matched)
n=8 Participants
LCZ696 200 mg, given as a single oral dose. Each healthy volunteer matched in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in group 2
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of LCZ696 Analytes (AHU377, LBQ657, and Valsartan)
AHU377
|
2540 ng*hr/mL
Standard Deviation 1010
|
6200 ng*hr/mL
Standard Deviation 2970
|
1580 ng*hr/mL
Standard Deviation 390
|
1740 ng*hr/mL
Standard Deviation 520
|
|
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of LCZ696 Analytes (AHU377, LBQ657, and Valsartan)
LBQ657
|
118000 ng*hr/mL
Standard Deviation 37000
|
173000 ng*hr/mL
Standard Deviation 99900
|
77900 ng*hr/mL
Standard Deviation 14700
|
83100 ng*hr/mL
Standard Deviation 14700
|
|
Area Under the Plasma Concentration-time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of LCZ696 Analytes (AHU377, LBQ657, and Valsartan)
Valsartan
|
28500 ng*hr/mL
Standard Deviation 16900
|
63800 ng*hr/mL
Standard Deviation 48700
|
21600 ng*hr/mL
Standard Deviation 5980
|
25300 ng*hr/mL
Standard Deviation 11800
|
PRIMARY outcome
Timeframe: From pre-dose on Day 1 until 96h post-dose (Day 5)Population: PK analysis set
Blood samples were taken on Day 1 (treatment day) within 60 minutes prior to dosing, then, 0.5,1,1.5,2,3,4,6,8,12 hours after the dosing and on Days 2, 3, 4 and 5 post dosing
Outcome measures
| Measure |
Participants With Mild Hepatic Impairment (HI)
n=8 Participants
LCZ696 200 mg, given as a single oral dose
|
Participants With Moderate Hepatic Impairment (HI)
n=8 Participants
LCZ696 200 mg, given as a single oral dose
|
Healthy Volunteers (Mild HI Matched)
n=8 Participants
LCZ696 200 mg, given as a single oral dose. Each healthy volunteer matched in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in group 1
|
Healthy Volunteers (Moderate HI Matched)
n=8 Participants
LCZ696 200 mg, given as a single oral dose. Each healthy volunteer matched in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in group 2
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUCinf)] of LCZ696 Analytes (AHU377, LBQ657, and Valsartan)
AHU377
|
2540 ng*hr/mL
Standard Deviation 1010
|
6200 ng*hr/mL
Standard Deviation 2980
|
1590 ng*hr/mL
Standard Deviation 390
|
1740 ng*hr/mL
Standard Deviation 519
|
|
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUCinf)] of LCZ696 Analytes (AHU377, LBQ657, and Valsartan)
LBQ657
|
121000 ng*hr/mL
Standard Deviation 41000
|
187000 ng*hr/mL
Standard Deviation 124000
|
78500 ng*hr/mL
Standard Deviation 14700
|
84100 ng*hr/mL
Standard Deviation 14800
|
|
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUCinf)] of LCZ696 Analytes (AHU377, LBQ657, and Valsartan)
Valsartan
|
28800 ng*hr/mL
Standard Deviation 16900
|
65600 ng*hr/mL
Standard Deviation 50100
|
21900 ng*hr/mL
Standard Deviation 5950
|
26500 ng*hr/mL
Standard Deviation 12400
|
PRIMARY outcome
Timeframe: From pre-dose on Day 1 until 96h post-dose (Day 5)Population: PK analysis set
Blood samples were taken on Day 1 (treatment day) within 60 minutes prior to dosing, then, 0.5,1,1.5,2,3,4,6,8,12 hours after the dosing and on Days 2, 3, 4 and 5 post dosing
Outcome measures
| Measure |
Participants With Mild Hepatic Impairment (HI)
n=8 Participants
LCZ696 200 mg, given as a single oral dose
|
Participants With Moderate Hepatic Impairment (HI)
n=8 Participants
LCZ696 200 mg, given as a single oral dose
|
Healthy Volunteers (Mild HI Matched)
n=8 Participants
LCZ696 200 mg, given as a single oral dose. Each healthy volunteer matched in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in group 1
|
Healthy Volunteers (Moderate HI Matched)
n=8 Participants
LCZ696 200 mg, given as a single oral dose. Each healthy volunteer matched in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in group 2
|
|---|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) for LCZ696 Analytes (AHU377, LBQ657, and Valsartan)
AHU377
|
2530 ng/mL
Standard Deviation 1400
|
4430 ng/mL
Standard Deviation 1760
|
1510 ng/mL
Standard Deviation 585
|
1410 ng/mL
Standard Deviation 445
|
|
Maximum Plasma Concentration (Cmax) for LCZ696 Analytes (AHU377, LBQ657, and Valsartan)
LBQ657
|
7730 ng/mL
Standard Deviation 1470
|
6690 ng/mL
Standard Deviation 917
|
7450 ng/mL
Standard Deviation 1320
|
6770 ng/mL
Standard Deviation 1710
|
|
Maximum Plasma Concentration (Cmax) for LCZ696 Analytes (AHU377, LBQ657, and Valsartan)
Valsartan
|
4000 ng/mL
Standard Deviation 2310
|
4180 ng/mL
Standard Deviation 2340
|
3880 ng/mL
Standard Deviation 1490
|
3730 ng/mL
Standard Deviation 1540
|
SECONDARY outcome
Timeframe: From the screening visit until Day 5Population: Safety set: The safety set includes all participants who received study treatment.
Adverse events, serious adverse events and death were monitored from screening to end of study
Outcome measures
| Measure |
Participants With Mild Hepatic Impairment (HI)
n=8 Participants
LCZ696 200 mg, given as a single oral dose
|
Participants With Moderate Hepatic Impairment (HI)
n=8 Participants
LCZ696 200 mg, given as a single oral dose
|
Healthy Volunteers (Mild HI Matched)
n=8 Participants
LCZ696 200 mg, given as a single oral dose. Each healthy volunteer matched in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in group 1
|
Healthy Volunteers (Moderate HI Matched)
n=8 Participants
LCZ696 200 mg, given as a single oral dose. Each healthy volunteer matched in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in group 2
|
|---|---|---|---|---|
|
Number of Participants With Adverse Events, Serious Adverse Events and Death
Adverse events (serious and non-serious)
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events, Serious Adverse Events and Death
Serious adverse events
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Adverse Events, Serious Adverse Events and Death
Deaths
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Moderate Hepatic Impaired Patients
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Healthy Volunteers (Mild HI Matched)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Healthy Volunteers (Moderate HI Matched)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Participants With Mild Hepatic Impairment (HI)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Moderate Hepatic Impaired Patients
n=8 participants at risk
Moderate hepatic impaired patients
|
Healthy Volunteers (Mild HI Matched)
n=8 participants at risk
LCZ696 200 mg, given as a single oral dose. Each healthy volunteer matched in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in group 1
|
Healthy Volunteers (Moderate HI Matched)
n=8 participants at risk
LCZ696 200 mg, given as a single oral dose. Each healthy volunteer matched in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in group 2
|
Participants With Mild Hepatic Impairment (HI)
n=8 participants at risk
LCZ696 200 mg, given as a single oral dose
|
|---|---|---|---|---|
|
Gastrointestinal disorders
DIARRHOEA
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
|
Investigations
BLOOD POTASSIUM DECREASED
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
|
Renal and urinary disorders
RENAL IMPAIRMENT
|
12.5%
1/8
|
0.00%
0/8
|
0.00%
0/8
|
0.00%
0/8
|
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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER