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NCT Number: 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

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.

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Key information

Conditions

PK of FG-4592 Digestive System Diseases Healthy Subjects Hepatic Insufficiency Liver Diseases

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

COMAC

Sofia, Bulgaria

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

FG-4592

Drug

Oral

Other names: ASP1517,, roxadustat

Primary outcomes

  1. 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)

  2. 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 outcomes

  1. Pharmacokinetic profile of FG-4592 in plasma

    Time frame: Days 1 to 5 (Day 7 for hepatic impaired subjects)

    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)

  2. Pharmacokinetic profile of FG-4592 in urine

    Time frame: Days 1 to 5 (Day 7 for hepatic impaired subjects)

    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%)

  3. Erythropoietin in plasma

    Time frame: Days 1 to 5 (Day 7 for hepatic impaired subjects)

    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

  4. Safety and tolerability of FG-4592

    Time frame: Screening (Days -22 to -2) to ESV (5 to 9 days after (early) discharge)

    Nature, frequency and severity of adverse events (AEs), vital signs, safety laboratory tests, electrocardiogram

Sponsors and collaborators

Lead sponsor

Astellas Pharma Europe B.V.

Industry

Collaborators

  • Kyntra Bio

Registry information

Official study 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

Important dates

Study start
2013
Primary completion
2013
Study completion
2013
First posted
Jun 11, 2014
Registry last updated
Jun 11, 2014

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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