Clinical trial NCT02161224: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: PK of FG-4592
Hepatic Insufficiency
Healthy Subjects
Keywords: Phase 1
FG-4592
Single dose
Moderate hepatic impairment
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: FibroGen
First posted: 2014-06-11
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Pharmacokinetic parameter of FG-4592 in plasma as measured by area under the concentration-time curve (AUC) extrapolated to infinity (AUCinf)
timeFrame: Days 1 to 5 (Day 7 for hepatic impaired subjects)
measure: Pharmacokinetic parameter of FG-4592 in plasma as measured by maximum concentration (Cmax)
timeFrame: Days 1 to 5 (Day 7 for hepatic impaired subjects)
Secondary outcomes:
measure: Pharmacokinetic profile of FG-4592 in plasma
timeFrame: Days 1 to 5 (Day 7 for hepatic impaired subjects)
measure: Pharmacokinetic profile of FG-4592 in urine
timeFrame: Days 1 to 5 (Day 7 for hepatic impaired subjects)
measure: Erythropoietin in plasma
timeFrame: Days 1 to 5 (Day 7 for hepatic impaired subjects)
measure: Safety and tolerability of FG-4592
timeFrame: Screening (Days -22 to -2) to ESV (5 to 9 days after (early) discharge)
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: COMAC
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Central contact
role: STUDY_DIRECTOR
References: