Evaluation of the Pharmacokinetics of Tropifexor in Subjects With Mild, Moderate, or Severe Hepatic Impairment Compared to Healthy Control Subjects
- Conditions
- Non-alcoholic Fatty Liver Disease
- Interventions
- Drug: LJN452
- Registration Number
- NCT03681457
- Lead Sponsor
- Novartis Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
- 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:
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1 - Normal Hepatic Function LJN452 Normal hepatic function - Control - control group Group 2 - Mild Hepatic Impairment LJN452 Mild hepatic impairment - Child-Pugh A (Score 5-6) Group 3 - Moderate Hepatic Impairment LJN452 Moderate hepatic impairment - Child-Pugh B (Score 7-9) Group 4 - Severe Hepatic Impairment LJN452 Severe hepatic impairment - Child-Pugh C (score 10-15)
- Primary Outcome Measures
Name Time Method Cmax Up to 8 days The maximum (peak) observed drug concentration after single dose administration (mass x volume-1)
Tmax Up to 8 days Time to reach the maximum (peak) plasma drug concentration after single dose administration (time)
AUClast Up to 8 days 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 Up to 8 days The area under the concentration-time curve from time zero to infinity (mass x time x volume-1)
T1/2 Up to 8 days The elimination half-life associated with the terminal slope of a semi-logarithmic concentration-time curve
CL/F Up to 8 days The apparent total body clearance of the drug from plasma (volume x time-1)
Vz/F Up to 8 days The apparent volume of distribution during the terminal phase
- Secondary Outcome Measures
Name Time Method fu Day 1 Fraction of analyte unbound calculated in-vitro
Cmax,u Day 1 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 Day 1 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 Day 1 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 Day 1 The apparent total body clearance of drug from the plasma of unbound drug (volume x time-1), calculated as CL/F/fu
Trial Locations
- Locations (1)
Novartis Investigative Site
🇺🇸Knoxville, Tennessee, United States