Mild and Moderate Renal ImpairmentPhase 1NCT01569815

Pharmacokinetics of LCZ696 in Subjects With Mild and Moderate Renal Impairment Compared to Healthy Subjects With Normal Renal Function

A Phase 1 study testing LCZ696 in people with Mild and Moderate Renal Impairment, run by Novartis Pharmaceuticals at 3 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Mild and Moderate Renal Impairment
What is being tested?: LCZ696
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 3 sitesin 3 countries
Study dates: Feb 2009to Aug 2014
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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:

Show all 21Show fewer

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

Who cannot join

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

Trial locations and contacts

3 sites in 3 countries.

Country

City, postcode or hospital

3 sites in 3 countries

Germany1 site

Novartis Investigative Site
Neuss, 41460

Other trials in Germany

Russia1 site

Novartis Investigative Site
Moscow, 117292

Other trials in Russia

Serbia1 site

Novartis Investigative Site
Belgrade

Other trials in Serbia

About this study

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

Conditions: Mild and Moderate Renal Impairment
Being tested: LCZ696
Keywords: Renal Impairment,, LCZ696
Medical subject headings: Lymphoma, Follicular, Renal Insufficiency

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

LCZ696Drug
LCZ696 400 mg once daily

Study groups in NCT01569815
Study group	Role	What they receive
LCZ696 400 mg	Experimental	LCZ696 400 mg once daily for 5 days Receives: Drug: LCZ696

What is being measured

The primary outcome is the main question the study is designed to answer.

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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: Day 5
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)
Measured: 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)
Measured: 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)
Measured: Day 1 and Day 5

Secondary outcomes (1)

Change in Mean 24-hours Sodium Clearance From Baseline to Day 7
Sodium clearance will be measured in urine from baseline until Day 7
Measured: From baseline to Day 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 2009Aug 2014

First posted3 Apr 2012 (estimated)
Study startFeb 2009
Primary completionAug 2014
Study completionAug 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Mild and Moderate Renal ImpairmentStudies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01569815
Sponsor's protocol ID: CLCZ696A2204
Other IDs: 2007-005480-96
Status last verified: Sep 2015
First submitted: 30 Mar 2012
Last updated: 19 Oct 2015
Results posted: Yes, on ClinicalTrials.gov

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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A Study of RG002C0106 Injection in Adult Participants With Normal Renal Function and Mild-to-Moderate Renal Impairment
Renal Impairments, IgA Nephropathy (IgAN)
RecruitingObservational study
Does Urinary TIMP2 and IGFBP7 Can Identify High Risk Patients of Progression From Mild and Moderate to Severe Acute Kidney Injury During Septic Shock?
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RecruitingPhase 4
Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Adolescents With Early Stages of Chronic Kidney Disease
Chronic Kidney Disease (Mild to Moderate), Albuminuria
RecruitingPhase 1
A Pharmacokinetics and Safety Study of Azvudine Tablets in Subjects With Mild-To-Moderate GFR Decline in Renal Insufficiency and in Healthy Subjects
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All Mild and Moderate Renal Impairment trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT01569815
Acronym / sponsor ID: CLCZ696A2204
Conditions: Mild and Moderate Renal Impairment
Keywords: Renal Impairment,, LCZ696
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Feb 2009
Primary completion: Aug 2014 (actual)
Study completion: Aug 2014 (actual)
First posted: 3 Apr 2012 (estimated)
Results: Posted 27 Aug 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
LCZ696 400 mg	Experimental	Drug: LCZ696LCZ696 400 mg once daily for 5 days

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (21 listed)

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;

Key exclusion criteria (6 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
LCZ696LCZ696 400 mg once daily	Drug	LCZ696 400 mg

Primary outcome

Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)

1 secondary outcome

Change in Mean 24-hours Sodium Clearance From Baseline to Day 7
Time frame: From baseline to Day 7

Results and safety

Results posted to the registry on 27 Aug 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Mild Renal Impaired	8	8
Mild Renal Impaired Matched Healthy Subjects	8	8
Moderate Renal Impaired Subjects	8	8
Moderate Renal Impaired Matched Healthy Subjects	8	8

Primary outcome: Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)

Time frame: Day 1 and day 5. Median (Full Range). Unit: hr

Measure	Mild Renal Impaired Subjects n = 8	Mild Renal Impaired Matched Healthy Subjects n = 8	Moderate Renal Impaired Subjects n = 8	Moderate Renal Impaired Matched Healthy Subjects n = 8
AHU377 day 1, single dose of LCZ696 400 mg	1 (0.5 to 2.0)	0.5 (0.5 to 1.0)	0.5 (0.5 to 4.0)	0.5 (0 to 2)
AHU377 day 5, multiple doses of LCZ696 400 mg Q.D.	1 (0.5 to 2.0)	0.5 (0.0 to 2.0)	0.5 (0.5 to 1.0)	0.5 (0.5 to 1.0)
LBQ657 day 1, single dose of LCZ696 400 mg	3 (2 to 4)	2 (2 to 3)	3 (2 to 8)	3 (2 to 3)
LBQ657 day 5, multiple doses of LCZ696 400 mg Q.D.	3 (2 to 4)	3 (2 to 3)	3 (2 to 4)	3 (2 to 4)
VAL489 day 1, single dose of LCZ696 400 mg	2.5 (2 to 3)	2 (2 to 4)	2 (1 to 6)	2 (1 to 3)
VAL489 day 5,multiple doses LCZ696 400 mg Q.D.	2.5 (1 to 4)	2 (1 to 3)	2 (2 to 2)	2 (2 to 2)

Primary outcome: Maximum Peak Plasma Concentration (Cmax) Observed After Single Dose (Day 1), and After Multiple Dose Administration (Day 5)

Time frame: Day 1, day 5. Mean (Standard Deviation). Unit: ng/mL

Measure	Mild Renal Impaired Subjects n = 8	Mild Renal Impaired Matched Healthy Subjects n = 8	Moderate Renal Impaired Subjects n = 8	Moderate Renal Impaired Matched Healthy Subjects n = 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)

Primary outcome: 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)

Time frame: Day 1 and day 5. Mean (Standard Deviation). Unit: ng*hr/mL

Measure	Mild Renal Impaired Subjects n = 8	Mild Renal Impaired Matched Healthy Subjects n = 8	Moderate Renal Impaired Subjects n = 8	Moderate Renal Impaired Matched Healthy Subjects n = 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)

Population analysed: FAS

Primary outcome: Elimination Half-life (t1/2) After Multiple Dose (Day 5) Administration

Time frame: Day 5. Mean (Standard Deviation). Unit: hr

Measure	Mild Renal Impaired Subjects n = 8	Mild Renal Impaired Matched Healthy Subjects n = 8	Moderate Renal Impaired Subjects n = 8	Moderate Renal Impaired Matched Healthy Subjects n = 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)

Population analysed: FAS

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
LCZ696 400 mg - Mild - Renal Impaired Patients	0 of 8 (0%)	7 of 8 (87.5%)	Not reported
LCZ696 400 mg - Mild - Matched Healthy Subjects	0 of 8 (0%)	3 of 8 (37.5%)	Not reported
LCZ696 400 mg - Moderate - Renal Impaired Patients	0 of 8 (0%)	8 of 8 (100%)	Not reported
LCZ696 400 mg - Moderate - Matched Healthy Subjects	0 of 8 (0%)	1 of 8 (12.5%)	Not reported
LCZ696 400 mg - All Healthy Subjects	0 of 16 (0%)	4 of 16 (25%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Mild and Moderate Renal Impairment

Active, not recruitingPhase 1
A Study of RG002C0106 Injection in Adult Participants With Normal Renal Function and Mild-to-Moderate Renal Impairment
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

3 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing LCZ696 in people with Mild and Moderate Renal Impairment, run by Novartis Pharmaceuticals at 3 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Germany, Russia, Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Time to Reach Maximum Peak Plasma Concentration (Tmax) After Single Dose (Day 1), and After Multiple Dose Administration (Day 5) (time frame: Day 1 and day 5). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01569815.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2015.