This is a Phase I study designed to characterize the pharmacokinetics (PK), safety, and tolerability of a single oral dose of FIA586 in participants with mild and moderate hepatic impairment (HI) compared to matched healthy participants.The information obtained in this study will help to determine whether dosage adjustment for FIA586 is necessary in patients with advanced liver fibrosis who have mild to moderate HI.
This is a Phase I, single-dose, open-label, parallel-group study in participants with mild (Child-Pugh A; n=8-10) and moderate (Child-Pugh B; n=8-10) hepatic impairment (HI) and matched healthy participants with normal hepatic function (n=8-20). The study is comprised of an up to 28-day screening period (Days -28 to 2), a baseline evaluation (Day -1) prior to dosing on Day 1, and a treatment period of 6 days (Days 1-6). Participants will remain domiciled up to Day 6 after the Study Completion procedures have been completed. On Day 1, participants will be given a single dose of FIA586 following an overnight fast. PK (plasma and urine) and biomarker samples will be taken prior to dosing of study treatment and up to 120 hours (Day 6) post- dose. On Day 6, after the last PK sample has been taken, Study Completion assessments will be performed, and the participant will be discharged, provided there are no safety or tolerability concerns as judged by the investigator. All participants will have a post-study safety contact conducted approximately 30 days after administration of study treatment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
54
FIA586 capsule
Novartis Investigative Site
Coral Gables, Florida, United States
Novartis Investigative Site
Orlando, Florida, United States
Maximum Observed Blood Concentrations (Cmax) for FIA586
Blood samples will be collected to measure Cmax at indicated time-points. Pharmacokinetic (PK) parameters will be calculated based on FIA586 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC MS/MS) method with a lower limit of quantification of 20 ng/mL. Cmax will be determined using non-compartmental methods.
Time frame: pre-dose, 0.25 hours, 0.5 hours, 1 hour, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 92 hours and 120 hours
Area Under Plasma Concentration-time Curve from time zero to the last measurable concentration sampling time (AUClast) for FIA586
Blood samples will be collected to measure AUClast at indicated time-points. Pharmacokinetic (PK) parameters will be calculated based on FIA586 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC MS/MS) method with a lower limit of quantification of 20 ng/mL. AUClast will be determined using non-compartmental methods.
Time frame: pre-dose, 0.25 hours, 0.5 hours, 1 hour, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 92 hours and 120 hours
Area Under Plasma Concentration-time Curve from Time Zero Extrapolated to Infinity (AUC[0-inf]) for FIA586
Blood samples will be collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic (PK) parameters will be calculated based on FIA586 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC MS/MS) method with a lower limit of quantification of 20 ng/mL. AUC\[0-inf\] will be determined using non-compartmental methods
Time frame: pre-dose, 0.25 hours, 0.5 hours, 1 hour, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 92 hours and 120 hours
Area Under Plasma Concentration-time Curve from time 0 to 48 hours (AUC0-48h) for FIA586
Blood samples will be collected to measure AUC0-48h at indicated time-points. Pharmacokinetic (PK) parameters will be calculated based on FIA586 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC MS/MS) method with a lower limit of quantification of 20 ng/mL. AUC0-48h will be determined using non-compartmental methods.
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Time frame: pre-dose, 0.25 hours, 0.5 hours, 1 hour, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours and 48 hours
Time to Reach Maximum Blood Concentrations (Tmax) for FIA586
Blood samples will be collected to measure Tmax at indicated time-points. Pharmacokinetic (PK) parameters will be calculated based on FIA586 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC MS/MS) method with a lower limit of quantification of 20 ng/mL. Tmax will be determined using non-compartmental methods.
Time frame: pre-dose, 0.25 hours, 0.5 hours, 1 hour, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 92 hours and 120 hours
Terminal Elimination Half-life (T1/2) for FIA586
Blood samples will be collected to measure T1/2 at indicated time-points. Pharmacokinetic (PK) parameters will be calculated based on FIA586 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC MS/MS) method with a lower limit of quantification of 20 ng/mL. T1/2 will be determined using non-compartmental methods.
Time frame: pre-dose, 0.25 hours, 0.5 hours, 1 hour, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 92 hours and 120 hours
Apparent Clearance (CL/F) of FIA586
Blood samples will be collected to estimate CL/F at indicated time-points. Pharmacokinetic (PK) parameters will be calculated based on FIA586 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC MS/MS) method with a lower limit of quantification of 20 ng/mL.
Time frame: pre-dose, 0.25 hours, 0.5 hours, 1 hour, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 92 hours and 120 hours
Apparent volume of distribution during terminal elimination phase (Vz/F) of FIA586
Blood samples will be collected to estimate Vz/F at indicated time-points. Pharmacokinetic (PK) parameters will be calculated based on FIA586 blood concentrations determined by a validated liquid chromatography and tandem mass spectrometry (LC MS/MS) method with a lower limit of quantification of 20 ng/mL.
Time frame: pre-dose, 0.25 hours, 0.5 hours, 1 hour, 1,5 hours, 2 hours, 3 hours, 4 hours, 6 hours, 8 hours, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 92 hours and 120 hours