NCT01569815

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
32

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Feb 2009

Longer than P75 for phase_1

Geographic Reach
3 countries

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2009

Completed
3.2 years until next milestone

First Submitted

Initial submission to the registry

March 30, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

April 3, 2012

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2014

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

August 27, 2015

Completed
Last Updated

October 19, 2015

Status Verified

September 1, 2015

Enrollment Period

5.5 years

First QC Date

March 30, 2012

Results QC Date

July 30, 2015

Last Update Submit

September 25, 2015

Conditions

Mild and Moderate Renal Impairment

Keywords

Renal Impairment,LCZ696

Outcome Measures

Primary Outcomes (8)

  • 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)

    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)

    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)

    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)

    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)

    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)

    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)

    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)

    Day 1 and Day 5

Secondary Outcomes (1)

  • Change in Mean 24-hours Sodium Clearance From Baseline to Day 7

    From baseline to Day 7

Study Arms (1)

LCZ696 400 mg

EXPERIMENTAL

LCZ696 400 mg once daily for 5 days

Drug: LCZ696

Interventions

LCZ696DRUG

LCZ696 400 mg once daily

LCZ696 400 mg

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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
  • +6 more criteria

You may not qualify if:

  • 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;

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Novartis Investigative Site

Neuss, 41460, Germany

Location

Novartis Investigative Site

Moscow, 117292, Russia

Location

Novartis Investigative Site

Belgrade, Serbia

Location

MeSH Terms

Conditions

Lymphoma, FollicularRenal Insufficiency

Interventions

sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Lymphoma, Non-HodgkinLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital Diseases

Results Point of Contact

Title
Study Director
Organization
Novartis Pharmaceuticals
862-778-8300

Study Officials

  • Novartis Pharmaceuticals

    Novartis Pharmaceuticals

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 30, 2012

First Posted

April 3, 2012

Study Start

February 1, 2009

Primary Completion

August 1, 2014

Study Completion

August 1, 2014

Last Updated

October 19, 2015

Results First Posted

August 27, 2015

Record last verified: 2015-09

Locations

SE(1)RU(1)DE(1)