Back to resultsA Study to Investigate the Exposure and Safety and Tolerability of a Single Dose of FG-4592 in Subjects With Moderately Diminished Liver Function Compared to Those With Normal Liver Function
Primary Purpose
PK of FG-4592, Hepatic Insufficiency, Healthy Subjects
Status
Completed
Phase
Phase 1
Locations
Bulgaria
Study Type
Interventional
Intervention
FG-4592
Sponsored by
About this trial
This is an interventional basic science trial for PK of FG-4592 focused on measuring Phase 1, FG-4592, Single dose, Moderate hepatic impairment
Eligibility Criteria
Inclusion Criteria:
Both healthy subjects and subjects with moderate hepatic impairment:
- Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations must be obtained from the subject prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
- Male subjects and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at screening and continuing throughout the study period and for 90 days after the study drug administration.
In addition, subjects with moderate hepatic impairment must also meet the following inclusion criteria:
- Subject has Child-Pugh classification Class B (moderate, 7 to 9 points) liver function impairment [screening].
Exclusion Criteria:
Both healthy subjects and subjects with moderate hepatic impairment:
- Female subject who has been pregnant within 6 months prior to screening or breastfeeding within 3 months before screening.
- Subject has a known or suspected hypersensitivity to FG-4592, or any components of the formulation used.
In addition, healthy subjects must also NOT meet the following exclusion criteria:
- Subject has any of the liver function tests (LFT) (Aspartate Aminotransferase [AST], Alanine Aminotransferase [ALT], Alkaline Phosphatase [ALP], Gamma Glutamyl Transferase [GGT], Total Bilirubin [TBL] above the upper limit of normal (ULN). In such a case the assessment may be repeated once [Day-1].
In addition, subjects with moderate hepatic impairment must also NOT meet the following exclusion criteria:
- Subject had a previous liver transplantation.
Sites / Locations
- COMAC
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
1: FG-4592 in subjects with moderate hepatic impairment
2: FG-4592 in healthy subjects
Arm Description
Outcomes
Primary Outcome Measures
Pharmacokinetic parameter of FG-4592 in plasma as measured by area under the concentration-time curve (AUC) extrapolated to infinity (AUCinf)
Pharmacokinetic parameter of FG-4592 in plasma as measured by maximum concentration (Cmax)
Secondary Outcome Measures
Pharmacokinetic profile of FG-4592 in plasma
AUC up to last quantifiable concentration (AUClast), AUC from 0 up to last quantifiable concentration based on unbound plasma concentration (AUClast,u), AUC from time point 0 to time point 24 hours (AUC0-24h), AUC from time point 0 to time point 24 hours based on unbound plasma concentration (AUC0-24h,u), unbound AUC extrapolated to infinity (AUCinf,u), unbound maximum concentration (observed) (Cmax,u), apparent total systemic clearance after extra-vascular dosing (CL/F), plasma clearance over bioavailability ratio based on unbound plasma (CLu/F), fraction unbound (fu), lag-time (time delay between drug administration and first observed concentration above the Limit of Quantification (LOQ) in plasma) (tlag), time to attain Cmax (tmax), apparent terminal elimination half-life (t1/2), apparent volume of distribution during terminal phase after oral administration (Vz/F), unbound apparent volume of distribution during terminal phase after oral administration (Vz,u/F)
Pharmacokinetic profile of FG-4592 in urine
renal clearance (CLR), renal clearance based on unbound concentration (CLR,u), renal clearance from time point 0 to 24 hours (CLR,0-24h), renal clearance from time point 0 to 24 hours based on unbound concentration (CLR,u 0-24h), amount of unchanged drug excreted into urine from time point 0 to infinity (Aeinf), amount of unchanged drug excreted into urine from time point 0 to infinity, percentage of dose (Aeinf%), amount of unchanged drug excreted into urine until the last observation time point (Aelast), amount of unchanged drug excreted into urine until the last observation time, percentage of dose (Aelast%), amount of drug excreted into urine from time point 0 to time point 24 hours (Ae0-24h), amount of drug excreted into urine from time point 0 to time point 24 hours, percentage of dose (Ae0-24h%)
Erythropoietin in plasma
maximum achievable pharmacologic effect (Emax), area under the concentration-time curve from 0 up to last quantifiable concentration based on EPO concentration (AUCE,last), tmax
Safety and tolerability of FG-4592
Nature, frequency and severity of adverse events (AEs), vital signs, safety laboratory tests, electrocardiogram
Full Information
NCT ID
NCT02161224
First Posted
June 9, 2014
Last Updated
June 9, 2014
Sponsor
Astellas Pharma Europe B.V.
Collaborators
FibroGen
1. Study Identification
Unique Protocol Identification Number
NCT02161224
Brief Title
A Study to Investigate the Exposure and Safety and Tolerability of a Single Dose of FG-4592 in Subjects With Moderately Diminished Liver Function Compared to Those With Normal Liver Function
Official Title
A Phase 1, Non-randomized, Open-label, Single-dose Study to Investigate the Pharmacokinetics, Safety and Tolerability of FG-4592 in Subjects With Moderate Hepatic Impairment and Healthy Subjects With Normal Hepatic Function
Study Type
Interventional
2. Study Status
Record Verification Date
June 2014
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Astellas Pharma Europe B.V.
Collaborators
FibroGen
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The effect of moderately diminished liver function on the exposure, safety and tolerability of a single dose of FG-4592 is studied in male and female subjects. The results are compared to the data gained from subjects with normal liver function.
Detailed Description
The effect of moderate hepatic impairment on the pharmacokinetics (PK), safety and tolerability of a single dose of FG-4592 in male and female subjects is investigated. Data obtained from these subjects are compared to data from BMI-, age- and sex-matched subjects with normal hepatic function. Both groups consist of 8 subjects.
Screening takes place from Days -22 to -2 before admission to the clinical unit on Day -1. Administration of the trial medication takes place on Day 1 under fasted conditions. Healthy subjects are discharged on Day 5 and subjects with moderate hepatic impairment on Day 7, if there is no reason to extend the stay. An end-of-study visit (ESV) takes place 5 to 9 days after (early) discharge.
Safety assessments are performed throughout the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PK of FG-4592, Hepatic Insufficiency, Healthy Subjects
Keywords
Phase 1, FG-4592, Single dose, Moderate hepatic impairment
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1: FG-4592 in subjects with moderate hepatic impairment
Arm Type
Experimental
Arm Title
2: FG-4592 in healthy subjects
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
FG-4592
Other Intervention Name(s)
ASP1517,, roxadustat
Intervention Description
Oral
Primary Outcome Measure Information:
Title
Pharmacokinetic parameter of FG-4592 in plasma as measured by area under the concentration-time curve (AUC) extrapolated to infinity (AUCinf)
Time Frame
Days 1 to 5 (Day 7 for hepatic impaired subjects)
Title
Pharmacokinetic parameter of FG-4592 in plasma as measured by maximum concentration (Cmax)
Time Frame
Days 1 to 5 (Day 7 for hepatic impaired subjects)
Secondary Outcome Measure Information:
Title
Pharmacokinetic profile of FG-4592 in plasma
Description
AUC up to last quantifiable concentration (AUClast), AUC from 0 up to last quantifiable concentration based on unbound plasma concentration (AUClast,u), AUC from time point 0 to time point 24 hours (AUC0-24h), AUC from time point 0 to time point 24 hours based on unbound plasma concentration (AUC0-24h,u), unbound AUC extrapolated to infinity (AUCinf,u), unbound maximum concentration (observed) (Cmax,u), apparent total systemic clearance after extra-vascular dosing (CL/F), plasma clearance over bioavailability ratio based on unbound plasma (CLu/F), fraction unbound (fu), lag-time (time delay between drug administration and first observed concentration above the Limit of Quantification (LOQ) in plasma) (tlag), time to attain Cmax (tmax), apparent terminal elimination half-life (t1/2), apparent volume of distribution during terminal phase after oral administration (Vz/F), unbound apparent volume of distribution during terminal phase after oral administration (Vz,u/F)
Time Frame
Days 1 to 5 (Day 7 for hepatic impaired subjects)
Title
Pharmacokinetic profile of FG-4592 in urine
Description
renal clearance (CLR), renal clearance based on unbound concentration (CLR,u), renal clearance from time point 0 to 24 hours (CLR,0-24h), renal clearance from time point 0 to 24 hours based on unbound concentration (CLR,u 0-24h), amount of unchanged drug excreted into urine from time point 0 to infinity (Aeinf), amount of unchanged drug excreted into urine from time point 0 to infinity, percentage of dose (Aeinf%), amount of unchanged drug excreted into urine until the last observation time point (Aelast), amount of unchanged drug excreted into urine until the last observation time, percentage of dose (Aelast%), amount of drug excreted into urine from time point 0 to time point 24 hours (Ae0-24h), amount of drug excreted into urine from time point 0 to time point 24 hours, percentage of dose (Ae0-24h%)
Time Frame
Days 1 to 5 (Day 7 for hepatic impaired subjects)
Title
Erythropoietin in plasma
Description
maximum achievable pharmacologic effect (Emax), area under the concentration-time curve from 0 up to last quantifiable concentration based on EPO concentration (AUCE,last), tmax
Time Frame
Days 1 to 5 (Day 7 for hepatic impaired subjects)
Title
Safety and tolerability of FG-4592
Description
Nature, frequency and severity of adverse events (AEs), vital signs, safety laboratory tests, electrocardiogram
Time Frame
Screening (Days -22 to -2) to ESV (5 to 9 days after (early) discharge)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Both healthy subjects and subjects with moderate hepatic impairment:
Independent Ethics Committee (IEC)-approved written Informed Consent and privacy language as per national regulations must be obtained from the subject prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
Male subjects and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 forms of birth control (1 of which must be a barrier method) starting at screening and continuing throughout the study period and for 90 days after the study drug administration.
In addition, subjects with moderate hepatic impairment must also meet the following inclusion criteria:
Subject has Child-Pugh classification Class B (moderate, 7 to 9 points) liver function impairment [screening].
Exclusion Criteria:
Both healthy subjects and subjects with moderate hepatic impairment:
Female subject who has been pregnant within 6 months prior to screening or breastfeeding within 3 months before screening.
Subject has a known or suspected hypersensitivity to FG-4592, or any components of the formulation used.
In addition, healthy subjects must also NOT meet the following exclusion criteria:
Subject has any of the liver function tests (LFT) (Aspartate Aminotransferase [AST], Alanine Aminotransferase [ALT], Alkaline Phosphatase [ALP], Gamma Glutamyl Transferase [GGT], Total Bilirubin [TBL] above the upper limit of normal (ULN). In such a case the assessment may be repeated once [Day-1].
In addition, subjects with moderate hepatic impairment must also NOT meet the following exclusion criteria:
Subject had a previous liver transplantation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Central contact
Organizational Affiliation
Astellas Pharma Europe B.V.
Official's Role
Study Director
Facility Information:
Facility Name
COMAC
City
Sofia
Country
Bulgaria
12. IPD Sharing Statement
Learn more about this trial
A Study to Investigate the Exposure and Safety and Tolerability of a Single Dose of FG-4592 in Subjects With Moderately Diminished Liver Function Compared to Those With Normal Liver Function
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