The purpose of this study is to evaluate the effect of various degrees of hepatic impairment on plasma pharmacokinetics (PK), safety and tolerability of TNO155. The results of this study will guide the Novartis recommendation regarding whether or not a dose adjustment may be needed when treating patients with hepatic impairment.
This is a study to evaluate the PK of TNO155 in participants with mild, moderate or severe hepatic impairment compared to matched healthy control participants with normal hepatic function. The study will be divided into 2 parts. Participants in the hepatic impairment groups will be staged by their respective degree of hepatic impairment (mild, moderate, or severe) according to a classification score determined at the screening visit and confirmed unchanged at the baseline visit. Each participant in the healthy control group may be matched to 1 or more evaluable participants with hepatic impairment with respect to age (± 10 years), body weight (± 20%), sex and smoking status (smoker vs. non smoker). Each participant in the control group can be matched to participants from any hepatic impairment group but cannot be matched to more than 1 participant from the same hepatic impairment group. All participants will be domiciled from Day -1 until Day 11. All participants should have a poststudy safety follow-up contact conducted approximately 30 days after administration of study treatment. The study will be considered complete once all the participants have finished the required assessments, dropped out, or been lost to follow-up before completing the required assessments.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Single oral dose of TNO155 on Day 1
Area under the concentration-versus-time curve (AUC) from time zero to the last measurable plasma concentration (AUClast) of TNO155
AUClast will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Time frame: Up to 240 hours post single dose
AUC from time zero to time "t" (AUC0-t) of TNO155
AUC0-t will be calculated as needed based on TNO155 plasma concentrations and non-compartmental methods. The definition of time "t" may be data-driven post-hoc to mitigate treatment bias due to within participant differences in Tlast between the treatments, or may be selected to allow between-study exposure comparisons that use a common time window.
Time frame: Up to 240 hours post single dose
AUC from time zero to infinity (AUCinf) of TNO155
AUCinf will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Time frame: Up to 240 hours post single dose
Maximum (peak) observed plasma concentration (Cmax) of TNO155
Cmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Time frame: Up to 240 hours post single dose
Time to reach maximum observed plasma concentration (Tmax) of TNO155
Tmax will be calculated based on TNO155 plasma concentrations and non-compartmental methods
Time frame: Up to 240 hours post single dose
Elimination half-life (T1/2) of TNO155
T1/2 will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Time frame: Up to 240 hours post single dose
Sampling time of the last measurable plasma concentration (Tlast) of TNO155
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Tlast will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Time frame: Up to 240 hours post single dose
Apparent plasma clearance (CL/F) of TNO155
CL/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Time frame: Up to 240 hours post single dose
Apparent volume of distribution during terminal phase (Vz/F) of TNO155
Vz/F will be calculated based on TNO155 plasma concentrations and non-compartmental methods.
Time frame: Up to 240 hours post single dose
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Incidence of AEs and SAEs, including changes in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs.
Time frame: Up to 30 days post single dose
Unbound Cmax (Cmax,u) of TNO155
Cmax,u will be calculated based on the unbound fraction of TNO155 in plasma.
Time frame: Up to 240 hours post single dose
Unbound AUClast (AUClast,u) of TNO155
AUClast,u will be calculated based on the unbound fraction of TNO155 in plasma.
Time frame: Up to 240 hours post single dose
Unbound AUCinf (AUCinf,u) of TNO155
AUCinf,u will be calculated based on the unbound fraction of TNO155 in plasma
Time frame: Up to 240 hours post single dose
Unbound CL/F (CL/F,u) of TNO155
CL/F,u will be calculated based on the unbound fraction of TNO155 in plasma.
Time frame: Up to 240 hours post single dose
Renal clearance (CLr) of TNO155
CLr will be calculated based on urinary excretion data of TNO155.
Time frame: Up to 240 hours post single dose
Apparent non-renal clearance (CLNR/F) of TNO155
CLNR/F will be calculated based on urinary excretion data of TNO155.
Time frame: Up to 240 hours post single dose
Fraction of dose excreted in urine (fe) of TNO155
Fe will be calculated based on urinary excretion data of TNO155.
Time frame: Up to 240 hours post single dose