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CompletedNCT01621633Updated Aug 10, 2015Results posted

A Study of LCZ696 in Subjects With Mild and Moderate Hepatic Impairment Compared With Normal Healthy Volunteers

A Phase 2 interventional study of LCZ696 in Hepatic Impairment, sponsored by Novartis Pharmaceuticals. Completed at 1 site in Germany. Open to participants aged 18 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2015-08-10.

Sponsored by Novartis Pharmaceuticals (part of Novartis) · Phase 2 and Interventional

Phase
Phase 2
Study type
Interventional
Enrollment
32
Allocation
Non-randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

This is a study to characterize the pharmacokinetics as well as safety and tolerability of a single oral dose of LCZ696 200 mg in subjects with mild and moderate hepatic impairment compared to matched healthy subjects

02

Conditions studied

  • Hepatic Impairment

Keywords

  • hepatic impairment
03

In context

Lead sponsor

Novartis Pharmaceuticals is the lead sponsor of 2,711 studies on the registry; 218 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 435 (75%) have results posted.

Browse Novartis Pharmaceuticals studies →All Novartis studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • All subjects:

    • Male and female subjects aged 18-75 years.
    • Body weight at least 55 kg with a body mass index between 18-35 kg/m2.

  • Hepatic impairment subjects:

    • Mild or moderate hepatic impairment.

Exclusion criteria

Exclusion Criteria:

  • All subjects:

    • Clinical manifestations of postural symptomatic hypotension at screening or baseline.
    • History of hypersensitivity to LCZ696 or to drugs of similar classes.

  • Hepatic impairment subjects:

    • Hepatic impairment due to non-liver disease.
    • Treatment with any vasodilator, autonomic alpha blocker or beta2 agonist within 2 weeks of dosing.
    • Encephalopathyy Stage III or IV.
    • Primary biliary liver cirrhosis or biliary obstruction.
    • History of gastro-intestinal bleeding within 3 months prior to screening.

  • Healthy subjects:

    • Any surgical or medical condition which might significantly alter the distribution, or excretion of drugs, or which may jeopardize the subject in case of participation in the study.
    • Use of prescription drugs, herbal supplements, and/or over-the-counter medication, dietary supplements (vitamins included) within 2 weeks prior to initial dosing.

Other protocol-defined inclusion/exclusion criteria may apply.

05

Study design

Phase
Phase 2
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
32 participants (actual)

Study arms

  • Experimental
    Group 1: mild hepatic impairment

    LCZ696 200 mg, given as a single oral dose

    Drug: LCZ696

  • Experimental
    Group 2: moderate hepatic impairment

    LCZ696 200 mg, given as a single oral dose

    Drug: LCZ696

  • Experimental
    Group 3: healthy volunteers

    LCZ696 200 mg, given as a single oral dose. Each healthy volunteer will match in race, age (±5 years), gender, weight (±15%) to an individual subject with hepatic impairment in groups 1 and 2

    Drug: LCZ696

Interventions

  • DrugLCZ696
06

What researchers measure

Primary outcomes

  1. 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)

    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

    Time frame: From pre-dose on Day 1 until 96h post-dose (Day 5)

  2. Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUCinf)] of LCZ696 Analytes (AHU377, LBQ657, and Valsartan)

    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

    Time frame: From pre-dose on Day 1 until 96h post-dose (Day 5)

  3. Maximum Plasma Concentration (Cmax) for LCZ696 Analytes (AHU377, LBQ657, and Valsartan)

    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

    Time frame: From pre-dose on Day 1 until 96h post-dose (Day 5)

Secondary outcomes

  1. Number of Participants With Adverse Events, Serious Adverse Events and Death

    Adverse events, serious adverse events and death were monitored from screening to end of study

    Time frame: From the screening visit until Day 5

07

Results

Posted Aug 10, 2015

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 flow — Overall Study
MilestoneParticipants With Mild Hepatic Impairment (HI)Participants With Moderate Hepatic Impairment (HI)Healthy Volunteers (Mild HI Matched)Healthy Volunteers (Moderate HI Matched)
Started8888
Completed8888
Not completed0000

Outcome measures

PrimaryArea 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)

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

Time frame:
From pre-dose on Day 1 until 96h post-dose (Day 5)
Reported as:
Mean · ng*hr/mL
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)
ng*hr/mLParticipants With Mild Hepatic Impairment (HI)Participants With Moderate Hepatic Impairment (HI)Healthy Volunteers (Mild HI Matched)Healthy Volunteers (Moderate HI Matched)
AHU3772540 ± 10106200 ± 29701580 ± 3901740 ± 520
LBQ657118000 ± 37000173000 ± 9990077900 ± 1470083100 ± 14700
Valsartan28500 ± 1690063800 ± 4870021600 ± 598025300 ± 11800
PrimaryArea Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUCinf)] of LCZ696 Analytes (AHU377, LBQ657, and Valsartan)

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

Time frame:
From pre-dose on Day 1 until 96h post-dose (Day 5)
Reported as:
Mean · ng*hr/mL
Area Under the Plasma Concentration-time Profile From Time Zero Extrapolated to Infinite Time [AUCinf)] of LCZ696 Analytes (AHU377, LBQ657, and Valsartan)
ng*hr/mLParticipants With Mild Hepatic Impairment (HI)Participants With Moderate Hepatic Impairment (HI)Healthy Volunteers (Mild HI Matched)Healthy Volunteers (Moderate HI Matched)
AHU3772540 ± 10106200 ± 29801590 ± 3901740 ± 519
LBQ657121000 ± 41000187000 ± 12400078500 ± 1470084100 ± 14800
Valsartan28800 ± 1690065600 ± 5010021900 ± 595026500 ± 12400
PrimaryMaximum Plasma Concentration (Cmax) for LCZ696 Analytes (AHU377, LBQ657, and Valsartan)

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

Time frame:
From pre-dose on Day 1 until 96h post-dose (Day 5)
Reported as:
Mean · ng/mL
Maximum Plasma Concentration (Cmax) for LCZ696 Analytes (AHU377, LBQ657, and Valsartan)
ng/mLParticipants With Mild Hepatic Impairment (HI)Participants With Moderate Hepatic Impairment (HI)Healthy Volunteers (Mild HI Matched)Healthy Volunteers (Moderate HI Matched)
AHU3772530 ± 14004430 ± 17601510 ± 5851410 ± 445
LBQ6577730 ± 14706690 ± 9177450 ± 13206770 ± 1710
Valsartan4000 ± 23104180 ± 23403880 ± 14903730 ± 1540
SecondaryNumber of Participants With Adverse Events, Serious Adverse Events and Death

Adverse events, serious adverse events and death were monitored from screening to end of study

Time frame:
From the screening visit until Day 5
Reported as:
Number · Participants
Number of Participants With Adverse Events, Serious Adverse Events and Death
ParticipantsParticipants With Mild Hepatic Impairment (HI)Participants With Moderate Hepatic Impairment (HI)Healthy Volunteers (Mild HI Matched)Healthy Volunteers (Moderate HI Matched)
Adverse events (serious and non-serious)0200
Serious adverse events0000
Deaths0000

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Moderate Hepatic Impaired Patients—0/8 (0%)2/8 (25%)
Healthy Volunteers (Mild HI Matched)—0/8 (0%)0/8 (0%)
Healthy Volunteers (Moderate HI Matched)—0/8 (0%)0/8 (0%)
Participants With Mild Hepatic Impairment (HI)—0/8 (0%)0/8 (0%)
Most frequent other events
Most frequent other events
EventModerate Hepatic Impaired PatientsHealthy Volunteers (Mild HI Matched)Healthy Volunteers (Moderate HI Matched)Participants With Mild Hepatic Impairment (HI)
DIARRHOEAGastrointestinal disorders1/80/80/80/8
BLOOD POTASSIUM DECREASEDInvestigations1/80/80/80/8
RENAL IMPAIRMENTRenal and urinary disorders1/80/80/80/8

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Participants With Mild Hepatic Impairment (HI)Participants With Moderate Hepatic Impairment (HI)Healthy Volunteers (Mild HI Matched)Healthy Volunteers (Moderate HI Matched)Total
Mean59.1 ± 7.9257.9 ± 11.6758.9 ± 8.6860.3 ± 11.2159.0 ± 9.54
Sex: Female, Male
Sex: Female, Male(Participants)Participants With Mild Hepatic Impairment (HI)Participants With Moderate Hepatic Impairment (HI)Healthy Volunteers (Mild HI Matched)Healthy Volunteers (Moderate HI Matched)Total
Female31318
Male575724
08

Study locations

1 site
  • Novartis Investigative Site
    Grünstadt, D-67269, Germany
09

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Sep 2012, a primary completion of Jan 2013 and a completion of Jan 2013. It does not say whether these dates are actual or estimated.

Results were first posted in Aug 2015, 2 years 7 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Jun 14, 2012
First posted
Jun 18, 2012
Start
Sep 2012
Primary completionActual
Jan 2013
CompletionActual
Jan 2013
Results first posted
Aug 10, 2015
Last update
Aug 10, 2015
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Aug 10, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01621633
Lead sponsor
Novartis Pharmaceuticals
Responsible party
Sponsor
First posted
Jun 18, 2012
Start date
Sep 2012
Primary completion
Jan 2013
Completion
Jan 2013
Results posted
Aug 10, 2015
Last update
Aug 10, 2015

Study contacts

Novartis Pharmaceuticals
study director · Novartis Pharmaceuticals

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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