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

NCT03681457 | Completed Phase 1 FDA Drug

• 1 other identifier: CLJN452A2109
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 3

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.

Conditions

Non-alcoholic Fatty Liver Disease

Keywords

LJN452; tropifexor; PK; safety; healthy subjects; hepatically impaired; Nonalcoholic Steatohepatitis; Nonalcoholic Fatty Liver Disease; NAFLD

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (5)

• fu

  Day 1

• Cmax,u

  Day 1

• AUClast,u

  Day 1

• AUCinf,u

  Day 1

• CL/F,u

  Day 1

Study Arms (4)

Group 1 - Normal Hepatic Function

OTHER

Normal hepatic function - Control - control group

Drug: LJN452

Group 2 - Mild Hepatic Impairment

EXPERIMENTAL

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

Drug: LJN452

Group 3 - Moderate Hepatic Impairment

EXPERIMENTAL

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

Drug: LJN452

Group 4 - Severe Hepatic Impairment

EXPERIMENTAL

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

Drug: LJN452

Interventions

LJN452 DRUG

Dose A single dose

Group 1 - Normal Hepatic Function; Group 2 - Mild Hepatic Impairment; Group 3 - Moderate Hepatic Impairment; Group 4 - Severe Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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:
• \- In good health as determined by past medical history, physical examination, ECG, laboratory tests, and urinalysis at Screening.
• Liver disease or liver injury
• Chronic infection with Hepatitis B or Hepatitis C
• History or presence of impaired renal function
• Hepatically Impaired Subjects:
• \- Hepatic impairment as defined by the Child-Pugh classification for severity of liver disease
• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (3)

Novartis Investigative Site

Orlando, Florida, 32806, United States

Location

Novartis Investigative Site

Orlando, Florida, 32809, United States

Location

Novartis Investigative Site

Knoxville, Tennessee, 37920, United States

Location

Related Links

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

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

tropifexor

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2018
• First Posted: September 24, 2018
• Study Start: September 24, 2018
• Primary Completion: September 25, 2019
• Study Completion: September 25, 2019
• Last Updated: December 14, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)