PK of FG-4592Phase 1NCT02161224
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
A Phase 1 study testing FG-4592 in people with PK of FG-4592 and Hepatic Insufficiency, run by Astellas Pharma Europe B.V. at 1 site in Bulgaria.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- PK of FG-4592, Hepatic Insufficiency, Healthy Subjects
- What is being tested?
- FG-4592
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteBulgaria
- Study dates
- Sep 2013to Dec 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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].
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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.
- Conditions
- PK of FG-4592, Hepatic Insufficiency, Healthy Subjects
- Being tested
- FG-4592
- Keywords
- Phase 1, FG-4592, Single dose, Moderate hepatic impairment
- Medical subject headings
- Hepatic Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FG-4592Drug
Also called ASP1517,, roxadustat
Oral
| Study group | Role | What they receive |
|---|---|---|
| 1: FG-4592 in subjects with moderate hepatic impairment | Experimental | Not described Receives: Drug: FG-4592 |
| 2: FG-4592 in healthy subjects | Experimental | Not described Receives: Drug: FG-4592 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetic parameter of FG-4592 in plasma as measured by area under the concentration-time curve (AUC) extrapolated to infinity (AUCinf)
Measured: Days 1 to 5 (Day 7 for hepatic impaired subjects)
Pharmacokinetic parameter of FG-4592 in plasma as measured by maximum concentration (Cmax)
Measured: Days 1 to 5 (Day 7 for hepatic impaired subjects)
Secondary outcomes (4)
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)
Measured: Days 1 to 5 (Day 7 for hepatic impaired subjects)
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%)
Measured: Days 1 to 5 (Day 7 for hepatic impaired subjects)
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
Measured: Days 1 to 5 (Day 7 for hepatic impaired subjects)
Safety and tolerability of FG-4592
Nature, frequency and severity of adverse events (AEs), vital signs, safety laboratory tests, electrocardiogram
Measured: Screening (Days -22 to -2) to ESV (5 to 9 days after (early) discharge)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2014 (estimated)
- Study startSep 2013
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PK of FG-4592Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Astellas Pharma Europe B.V.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Kyntra Bio
- Responsible party
- Sponsor
- Investigators
- Central contact, Study director, Astellas Pharma Europe B.V.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02161224
- Sponsor's protocol ID
- 1517-CL-0513
- Other IDs
- 2013-001533-41
- Status last verified
- Jun 2014
- First submitted
- 9 Jun 2014
- Last updated
- 11 Jun 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02161224
- Acronym / sponsor ID
- 1517-CL-0513
- Conditions
- PK of FG-4592, Hepatic Insufficiency, Healthy Subjects
- Keywords
- Phase 1, FG-4592, Single dose, Moderate hepatic impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Astellas Pharma Europe B.V.Industry (pharma, biotech, devices)
- Collaborators
- Kyntra Bio
- Study start
- Sep 2013
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 11 Jun 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1: FG-4592 in subjects with moderate hepatic impairment | Experimental | Drug: FG-4592 |
| 2: FG-4592 in healthy subjects | Experimental | Drug: FG-4592 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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].
Key exclusion criteria (7 listed)
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FG-4592Also: ASP1517,, roxadustatOral | Drug | 1: FG-4592 in subjects with moderate hepatic impairment, 2: FG-4592 in healthy subjects |
Primary outcome
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)
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)
4 secondary outcomes
Pharmacokinetic profile of FG-4592 in plasma
Time frame: Days 1 to 5 (Day 7 for hepatic impaired subjects)
Pharmacokinetic profile of FG-4592 in urine
Time frame: Days 1 to 5 (Day 7 for hepatic impaired subjects)
Erythropoietin in plasma
Time frame: Days 1 to 5 (Day 7 for hepatic impaired subjects)
Safety and tolerability of FG-4592
Time frame: Screening (Days -22 to -2) to ESV (5 to 9 days after (early) discharge)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2014.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Central contact study director
Astellas Pharma Europe B.V.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing FG-4592 in people with PK of FG-4592 and Hepatic Insufficiency, run by Astellas Pharma Europe B.V. at 1 site in Bulgaria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Bulgaria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2014.