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

Non-alcoholic Fatty Liver Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03681457
• Other study ID #: CLJN452A2109
• Status: Completed
• Phase: Phase 1
• Start date: September 24, 2018
• Est. completion date: September 25, 2019

Study information

• Verified date: September 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: September 25, 2019
• Est. primary completion date: September 25, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease

Intervention

Drug:
• LJN452
Dose A single dose

Locations

Country	Name	City	State
United States	Novartis Investigative Site	Knoxville	Tennessee
United States	Novartis Investigative Site	Orlando	Florida
United States	Novartis Investigative Site	Orlando	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cmax	The maximum (peak) observed drug concentration after single dose administration (mass x volume-1)	Up to 8 days
Primary	Tmax	Time to reach the maximum (peak) plasma drug concentration after single dose administration (time)	Up to 8 days
Primary	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
Primary	AUCinf	The area under the concentration-time curve from time zero to infinity (mass x time x volume-1)	Up to 8 days
Primary	T1/2	The elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve	Up to 8 days
Primary	CL/F	The apparent total body clearance of the drug from plasma (volume x time-1)	Up to 8 days
Primary	Vz/F	The apparent volume of distribution during the terminal phase	Up to 8 days
Secondary	fu	Fraction of analyte unbound calculated in-vitro	Day 1
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

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