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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: LJN452

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • Novartis Investigative Site
    • Orlando, Florida, United States, 32809
      • Novartis Investigative Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Group 1 - Normal Hepatic Function; Normal hepatic function - Control - control group	Drug: LJN452; Dose A single dose
EXPERIMENTAL: Group 2 - Mild Hepatic Impairment; Mild hepatic impairment - Child-Pugh A (Score 5-6)	Drug: LJN452; Dose A single dose
EXPERIMENTAL: Group 3 - Moderate Hepatic Impairment; Moderate hepatic impairment - Child-Pugh B (Score 7-9)	Drug: LJN452; Dose A single dose
EXPERIMENTAL: Group 4 - Severe Hepatic Impairment; Severe hepatic impairment - Child-Pugh C (score 10-15)	Drug: LJN452; Dose A single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	The maximum (peak) observed drug concentration after single dose administration (mass x volume-1)	Up to 8 days
Tmax	Time to reach the maximum (peak) plasma drug concentration after single dose administration (time)	Up to 8 days
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)	Up to 8 days
AUCinf	The area under the concentration-time curve from time zero to infinity (mass x time x volume-1)	Up to 8 days
T1/2	The elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve	Up to 8 days
CL/F	The apparent total body clearance of the drug from plasma (volume x time-1)	Up to 8 days
Vz/F	The apparent volume of distribution during the terminal phase	Up to 8 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
fu	Fraction of analyte unbound calculated in-vitro	Day 1
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	Day 1
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	Day 1
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	Day 1
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	Day 1

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CCLJN452A2109 can be found on the Novartis Clinical Trial Results Website
• A Plain Language Trial Summary is available on novartisclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 24, 2018
• Primary Completion (ACTUAL): September 25, 2019
• Study Completion (ACTUAL): September 25, 2019

Study Registration Dates

• First Submitted: September 11, 2018
• First Submitted That Met QC Criteria: September 21, 2018
• First Posted (ACTUAL): September 24, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 14, 2020
• Last Update Submitted That Met QC Criteria: December 10, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: safety; PK; Nonalcoholic Steatohepatitis; NAFLD; healthy subjects; Nonalcoholic Fatty Liver Disease; LJN452; tropifexor; hepatically impaired
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: CLJN452A2109

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No