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Evaluation of the Pharmacokinetics of Tropifexor in Subjects With Mild, Moderate, or Severe Hepatic Impairment Compared to Healthy Control Subjects

Primary Purpose

Non-alcoholic Fatty Liver Disease

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
LJN452
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-alcoholic Fatty Liver Disease focused on measuring LJN452, tropifexor, PK, safety, healthy subjects, hepatically impaired, Nonalcoholic Steatohepatitis, Nonalcoholic Fatty Liver Disease, NAFLD

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

All subjects:

Inclusions Criteria:

  • Subjects must weight at least 50 kg, with a BMI within the range of 18 to 38 kg/m2
  • Must be willing to remain in the clinical research unit as required by the protocol

Exclusion Criteria:

  • Use of other study drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations
  • History of hypersensitivity to the study treatment or to drugs of similar chemical classes
  • Pregnant or nursing women
  • Women of child-bearing potential

Healthy Volunteers:

Inclusion Criteria:

- In good health as determined by past medical history, physical examination, ECG, laboratory tests, and urinalysis at Screening.

Exclusion Criteria:

  • Liver disease or liver injury
  • Chronic infection with Hepatitis B or Hepatitis C
  • History or presence of impaired renal function

Hepatically Impaired Subjects:

Inclusion Criteria:

- Hepatic impairment as defined by the Child-Pugh classification for severity of liver disease

Exclusion Criteria:

  • Severe complications of liver disease within the preceding 3 months
  • Emergency room visit or hospitalization due to liver disease within the preceding 3 months for mildly and moderately hepatically impaired subjects, and within the preceding 1 month for severely hepatically impaired subjects
  • Subject has received liver transplant at any time in the past and is on immunosuppressant therapy
  • Acute Hepatitis B or Hepatitis C infection

Other protocol-defined inclusion/exclusion criteria may apply.

Sites / Locations

  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Other

Experimental

Experimental

Experimental

Arm Label

Group 1 - Normal Hepatic Function

Group 2 - Mild Hepatic Impairment

Group 3 - Moderate Hepatic Impairment

Group 4 - Severe Hepatic Impairment

Arm Description

Normal hepatic function - Control - control group

Mild hepatic impairment - Child-Pugh A (Score 5-6)

Moderate hepatic impairment - Child-Pugh B (Score 7-9)

Severe hepatic impairment - Child-Pugh C (score 10-15)

Outcomes

Primary Outcome Measures

Cmax
The maximum (peak) observed drug concentration after single dose administration (mass x volume-1)
Tmax
Time to reach the maximum (peak) plasma drug concentration after single dose administration (time)
AUClast
The area under the concentration-time curve from time zero to the time of the last quantifiable concentration sampling time (mass x time x volume-1)
AUCinf
The area under the concentration-time curve from time zero to infinity (mass x time x volume-1)
T1/2
The elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve
CL/F
The apparent total body clearance of the drug from plasma (volume x time-1)
Vz/F
The apparent volume of distribution during the terminal phase

Secondary Outcome Measures

fu
Fraction of analyte unbound calculated in-vitro
Cmax,u
The maximum (peak) observed plasma drug concentration after single dose administration (Cmax) of unbound drug (mass x time x volume-1), calculated as Cmax*fu
AUClast,u
The area under the concentration-time curve from time zero to the last quantifiable concentration sampling time of unbound drug (mass x time x volume-1), calculated as AUClast*fu
AUCinf,u
The area under the concentration-time curve from time zero to infinity of unbound drug (mass x time x volume-1), calculated as AUCinf*fu
CL/F,u
The apparent total body clearance of drug from the plasma of unbound drug (volume x time-1), calculated as CL/F/fu

Full Information

First Posted
September 11, 2018
Last Updated
December 10, 2020
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT03681457
Brief Title
Evaluation of the Pharmacokinetics of Tropifexor in Subjects With Mild, Moderate, or Severe Hepatic Impairment Compared to Healthy Control Subjects
Official Title
A Phase 1, Open-label, Single-dose, Multi-center, Parallel Group Study to Evaluate the Pharmacokinetics of Tropifexor (LJN452) in Subjects With Mild, Moderate or Severe Hepatic Impairment Compared to Healthy Control Subjects
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
September 24, 2018 (Actual)
Primary Completion Date
September 25, 2019 (Actual)
Study Completion Date
September 25, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary purpose of this study is to evaluate the effect of hepatic impairment on the systemic exposure of tropifexor and to evaluate the safety of tropifexor in subjects with hepatic impairment. The results of this study will support treatment and dosing decisions for patients with varying degrees of hepatic impairment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-alcoholic Fatty Liver Disease
Keywords
LJN452, tropifexor, PK, safety, healthy subjects, hepatically impaired, Nonalcoholic Steatohepatitis, Nonalcoholic Fatty Liver Disease, NAFLD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
42 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1 - Normal Hepatic Function
Arm Type
Other
Arm Description
Normal hepatic function - Control - control group
Arm Title
Group 2 - Mild Hepatic Impairment
Arm Type
Experimental
Arm Description
Mild hepatic impairment - Child-Pugh A (Score 5-6)
Arm Title
Group 3 - Moderate Hepatic Impairment
Arm Type
Experimental
Arm Description
Moderate hepatic impairment - Child-Pugh B (Score 7-9)
Arm Title
Group 4 - Severe Hepatic Impairment
Arm Type
Experimental
Arm Description
Severe hepatic impairment - Child-Pugh C (score 10-15)
Intervention Type
Drug
Intervention Name(s)
LJN452
Intervention Description
Dose A single dose
Primary Outcome Measure Information:
Title
Cmax
Description
The maximum (peak) observed drug concentration after single dose administration (mass x volume-1)
Time Frame
Up to 8 days
Title
Tmax
Description
Time to reach the maximum (peak) plasma drug concentration after single dose administration (time)
Time Frame
Up to 8 days
Title
AUClast
Description
The area under the concentration-time curve from time zero to the time of the last quantifiable concentration sampling time (mass x time x volume-1)
Time Frame
Up to 8 days
Title
AUCinf
Description
The area under the concentration-time curve from time zero to infinity (mass x time x volume-1)
Time Frame
Up to 8 days
Title
T1/2
Description
The elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve
Time Frame
Up to 8 days
Title
CL/F
Description
The apparent total body clearance of the drug from plasma (volume x time-1)
Time Frame
Up to 8 days
Title
Vz/F
Description
The apparent volume of distribution during the terminal phase
Time Frame
Up to 8 days
Secondary Outcome Measure Information:
Title
fu
Description
Fraction of analyte unbound calculated in-vitro
Time Frame
Day 1
Title
Cmax,u
Description
The maximum (peak) observed plasma drug concentration after single dose administration (Cmax) of unbound drug (mass x time x volume-1), calculated as Cmax*fu
Time Frame
Day 1
Title
AUClast,u
Description
The area under the concentration-time curve from time zero to the last quantifiable concentration sampling time of unbound drug (mass x time x volume-1), calculated as AUClast*fu
Time Frame
Day 1
Title
AUCinf,u
Description
The area under the concentration-time curve from time zero to infinity of unbound drug (mass x time x volume-1), calculated as AUCinf*fu
Time Frame
Day 1
Title
CL/F,u
Description
The apparent total body clearance of drug from the plasma of unbound drug (volume x time-1), calculated as CL/F/fu
Time Frame
Day 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
All subjects: Inclusions Criteria: Subjects must weight at least 50 kg, with a BMI within the range of 18 to 38 kg/m2 Must be willing to remain in the clinical research unit as required by the protocol Exclusion Criteria: Use of other study drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations History of hypersensitivity to the study treatment or to drugs of similar chemical classes Pregnant or nursing women Women of child-bearing potential Healthy Volunteers: Inclusion Criteria: - In good health as determined by past medical history, physical examination, ECG, laboratory tests, and urinalysis at Screening. Exclusion Criteria: Liver disease or liver injury Chronic infection with Hepatitis B or Hepatitis C History or presence of impaired renal function Hepatically Impaired Subjects: Inclusion Criteria: - Hepatic impairment as defined by the Child-Pugh classification for severity of liver disease Exclusion Criteria: Severe complications of liver disease within the preceding 3 months Emergency room visit or hospitalization due to liver disease within the preceding 3 months for mildly and moderately hepatically impaired subjects, and within the preceding 1 month for severely hepatically impaired subjects Subject has received liver transplant at any time in the past and is on immunosuppressant therapy Acute Hepatitis B or Hepatitis C infection Other protocol-defined inclusion/exclusion criteria may apply.
Facility Information:
Facility Name
Novartis Investigative Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Facility Name
Novartis Investigative Site
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Facility Name
Novartis Investigative Site
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37920
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.novctrd.com/ctrdweb/trialresult/trialresults/pdf?trialResultId=17722
Description
Results for CCLJN452A2109 can be found on the Novartis Clinical Trial Results Website
URL
https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=555
Description
A Plain Language Trial Summary is available on novartisclinicaltrials.com

Learn more about this trial

Evaluation of the Pharmacokinetics of Tropifexor in Subjects With Mild, Moderate, or Severe Hepatic Impairment Compared to Healthy Control Subjects

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