Pharmacokinetics Study of FIA586 in Participants With Mild and Moderate Hepatic Impairment

NCT04993157 | Completed Phase 1 FDA Drug

• 1 other identifier: CFIA586A02101
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Hepatic Impairment

Keywords

Hepatic Impairment; NASH; Child-Pugh classification; FIA586

Outcome Measures

Primary Outcomes (8)

• 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.

  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.

  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

  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.

  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.

  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.

  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.

  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.

  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

Study Arms (3)

Group 1: Healthy participants with normal hepatic function

EXPERIMENTAL

Each participant will receive a single dose of FIA586

Drug: FIA586

Group 2: Participants with mild hepatic impairment

EXPERIMENTAL

Each participant will receive a single dose of FIA586

Drug: FIA586

Group 3: Participants with moderate hepatic impairment

EXPERIMENTAL

Each participant will receive a single dose of FIA586

Drug: FIA586

Interventions

FIA586 DRUG

FIA586 capsule

Group 1: Healthy participants with normal hepatic function; Group 2: Participants with mild hepatic impairment; Group 3: Participants with moderate hepatic impairment

Eligibility Criteria

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

You may qualify if:

• All Participants:
• Male and non-childbearing potential female participants 18 to 70 years of age (inclusive) at Screening.
• Must weigh at least 50.0 kg and must have a body mass index (BMI) within the range of 18.0 to - 38.0 kg/m2 at Screening.
• Must be a non-smoker or agree to smoke no more than 5 cigarettes (or equivalent) per day, and maintain the same smoking status from Screening until the Study Completion (Day -28 to Day 6).
• Healthy participants (Group 1)
• Must be in good health as determined by past medical history, physical examination, vital signs, ECG, and laboratory tests at Screening.
• Each participant must match in age (±10 years), gender, weight (±15%), and smoking status (smoker or non-smoker) to an individual participant in at least one HI group but not to more than 1 participant in the same HI group.
• Participants with mild and moderate HI (Groups 2 and 3)
• Must satisfy the criteria for HI as evidenced by a Child-Pugh class of A or B at Screening:
• Class A; Mild; Child-Pugh score 5-6
• Class B; Moderate; Child-Pugh score 7-9

You may not qualify if:

• All participants:
• Use of other investigational drugs within the last 30 days or 5 half-lives prior to dosing of study treatment, whichever is longer.
• Known history of, or current clinically significant arrhythmias. Have clinically significant ECG abnormality or history of long-QT syndrome.
• Myocardial infarction \< 5 years prior to Screening.
• Recent (within the last 3 years of Screening) or recurrent history of autonomic dysfunction (e.g. recurrent episodes of fainting or palpitations).
• History of immunodeficiency diseases or have a positive HIV test result at Screening.
• History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 3 years of Screening, regardless of whether there is evidence of local recurrence or metastases.
• Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs (apart from cholecystectomy), or which may jeopardize the participants in case of participation in the study. The investigator should make this determination in consideration of the participant's medical history and/or clinical or laboratory evidence of any of the following:
• Inflammatory bowel disease, peptic ulcers, gastrointestinal including rectal bleeding within 3 months prior to Screening.
• Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection.
• Pancreatic injury or pancreatitis.
• Healthy participants (Group 1):
• Any single parameter of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), or alkaline phosphatase (ALP) exceeding 1.2 × upper limit of normal (ULN) or ≥ 1.5 × ULN total bilirubin (TBL) OR any elevation above ULN of more than one parameter of ALT, AST, GGT, ALP, or serum bilirubin at screening.
• Known to have Gilbert's syndrome.
• Hemoglobin levels below 12.0 g/dL for males and 11.0 g/dL for females at Screening or Baseline.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (2)

Novartis Investigative Site

Coral Gables, Florida, 33124, United States

Location

Novartis Investigative Site

Orlando, Florida, 32809, United States

Location

Related Links

• Results for CFIA586A02101 from the Novartis Clinical Trials website
• Plain Lanuguage Trial Summary

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: August 3, 2021
• First Posted: August 6, 2021
• Study Start: December 10, 2021
• Primary Completion: June 28, 2022
• Study Completion: June 28, 2022
• Last Updated: June 20, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)