Pharmacokinetics of FG-4592Phase 1NCT02252731
A Study to Evaluate the Effects of Multiple Doses of FG-4592 on the Exposure, Safety and Tolerability and Effect of Warfarin in Healthy Subjects
A Phase 1 study testing Warfarin and FG-4592 in people with Pharmacokinetics of FG-4592 and Healthy Subjects, run by Astellas Pharma Europe B.V. at 1 site in Germany.
Trial summary
This study will determine the effect of multiple doses of FG-4592 on the pharmacokinetics (PK) of a single dose of warfarin. It will evaluate the safety and tolerability of warfarin alone and in combination with multiple doses of FG-4592, and will evaluate the effect of multiple doses of FG-4592 on the… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Pharmacokinetics of FG-4592, Healthy Subjects
- What is being tested?
- Warfarin and FG-4592
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteGermany
- Study dates
- Sep 2013to Nov 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control.
- Male subject must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.
- Female subject must be either of non-childbearing potential or, if of childbearing potential, must have a negative pregnancy test at screening and Day -1 and must use two forms of birth control.
- Female subject must not donate ova starting at screening and throughout the study period and for 28 days after the final study drug administration.
Who cannot join
- Subject has a known or suspected hypersensitivity to FG 4592, warfarin, or any components of the formulations used.
- Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to admission to the clinical unit [Day -1].
- Subject is lactose intolerant.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-label, One-sequence Crossover Study to Evaluate the Effect of Multiple Doses of FG 4592 on the Pharmacokinetics of Warfarin in Healthy Subjects
This study will determine the effect of multiple doses of FG-4592 on the pharmacokinetics (PK) of a single dose of warfarin. It will evaluate the safety and tolerability of warfarin alone and in combination with multiple doses of FG-4592, and will evaluate the effect of multiple doses of FG-4592 on the pharmacodynamics (PD) of warfarin.
Read the detailed description
The study consists of 2 periods, separated by a washout period (a minimum of 14 days after warfarin dosing on Day 1, Period 1). Screening takes place from Day -22 to Day -2.
Subjects are admitted to the clinical unit on Day -1 of Period 1. On Day 1 of the first period, subjects receive a single oral dose of warfarin. After completion of all assessments on Day 8, subjects are discharged from the clinical unit on the condition that there are no medical reasons for a prolonged stay. They return to the clinical unit on Day -1 of the second period, after the washout period.
In Period 2, the subjects receive multiple doses of FG 4592. On Day 7 of Period 2, FG 4592 is given concomitantly with warfarin. After completion of all assessments on Day 16 of Period 2, subjects are discharged from the clinic on the condition that there are no medical reasons for a prolonged stay. The subjects return for an End of Study Visit (ESV) 5 to 9 days after the last assessment of Period 2 (or after early withdrawal).
Safety assessments are performed throughout the study. Blood and urine samples are collected for PK and PD assessments.
- Conditions
- Pharmacokinetics of FG-4592, Healthy Subjects
- Being tested
- Warfarin, FG-4592
- Keywords
- Phase I, FG-4592, Warfarin, Pharmacokinetics, Pharmacodynamics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
WarfarinDrug
Also called Coumadin®
Oral
FG-4592Drug
Also called ASP1517,, roxadustat
Oral
| Study group | Role | What they receive |
|---|---|---|
| warfarin and FG-4592 | Experimental | Single dose of warfarin and Multiple doses of FG-4592 in combination with a single dose of warfarin Receives: Drug: Warfarin; Drug: FG-4592 |
What is being measured
The primary outcome is the main question the study is designed to answer.
PK of S-warfarin and R-warfarin in plasma measured by area under the curve from the time of dosing extrapolated to time infinity (AUCinf)
Measured: Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)
PK of S-warfarin and R-warfarin in plasma measured by maximum concentration (Cmax)
Measured: Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)
Secondary outcomes (5)
PK profile of S-warfarin and R-warfarin in plasma
area under the concentration-time curve from the time of dosing to the last measurable concentration (Clast) (AUClast), unbound AUC from the time of dosing to Clast (AUClast,u), AUC from the time of dosing extrapolated to time infinity (AUCinf), unbound AUC extrapolated to infinity (AUCinf,u), maximum unbound plasma concentration (Cmax,u), apparent total body clearance after extra-vascular dosing (CL/F), unbound apparent total body clearance after extravascular dosing (CLu/F), fraction unbound (fu), time interval between the time of dosing and the first measurable concentration (tlag), time of the maximum concentration (tmax), terminal elimination half-life (t1/2), apparent volume of distribution during the terminal elimination phase after single extravascular dosing (Vz/F), unbound apparent volume of distribution during terminal phase after oral administration (Vz,u/F)
Measured: Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)
PK profile of FG-4592 in plasma
AUC from time point 0 to time point 24 hours (AUC0-24h), AUClast, AUCinf , Cmax, concentration at pre-dose for repeated dosing (Ctrough), tmax, t1/2, CL/F, and Vz/F
Measured: Period 2 (Day 1 to Day 15)
PK profile of FG-4592 in urine
renal clearance (CLR), unbound CLR from time point 0 to 24 hours (CLR,0-24h), cumulative amount of drug excreted unchanged into urine from time of dosing extrapolated to time infinity (Aeinf), percent of drug excreted unchanged into urine from time of dosing extrapolated to time infinity in percent of dose (Aeinf%), cumulative amount of drug excreted unchanged into urine, from time of dosing up to the collection time of the last measurable concentration (Aelast), percent of drug excreted into urine from time of dosing up to the collection time of the last measurable concentration in percent of dose (Aelast%), cumulative amount of drug excreted unchanged into urine, from time of dosing up to the collection time of 24 hours (Ae0 24h), cumulative amount of drug excreted unchanged into urine, from time of dosing up to the collection time of 24 hours in percent of dose (Ae0-24h%)
Measured: Period 2 (Day 7 to Day 8)
Pharmacodynamics profile of warfarin in plasma
area under the Prothrombin Time (PT)-time curve from the time of dosing until the last sample collected (AUCPT,last), maximal PT (PTmax), time to reach PTmax (tPT,max), area under the International Normalized Ratio (INR)-time curve from the time of dosing until the last sample collected (AUCINR,last), maximal INR after Drug Administration (INRmax), time to reach the INRmax (tINR,max)
Measured: Period 1 Day 1 to to ESV (5 to 9 days after the last protocol defined assessment of Period 2 (or after early withdrawal))
Safety profile
Safety profile includes Adverse Events (AEs), vital signs, physical examination, laboratory tests, electrocardiogram (ECG)
Measured: Screening (Day -22 to Day -2) to ESV (5 to 9 days after the last protocol defined assessment of Period 2 (or after early withdrawal))
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2014 (estimated)
- Study startSep 2013
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pharmacokinetics 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 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
- Study Physician, Study director, Astellas Pharma Europe B.V.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02252731
- Sponsor's protocol ID
- 1517-CL-0509
- Other IDs
- 2013-001043-31
- Status last verified
- Sep 2014
- First submitted
- 10 Jun 2014
- Last updated
- 30 Sep 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Groenendaal-van de Meent D, den Adel M, Rijnders S, Krebs-Brown A, Kerbusch V, Golor G, Schaddelee M. The Hypoxia-inducible Factor Prolyl-Hydroxylase Inhibitor Roxadustat (FG-4592) and Warfarin in Healthy Volunteers: A Pharmacokinetic and Pharmacodynamic Drug-Drug Interaction Study. Clin Ther. 2016 Apr;38(4):918-28. doi: 10.1016/j.clinthera.2016.02.010. Epub 2016 Mar 4.
PubMed 26947173
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, One-sequence Crossover Study to Evaluate the Effect of Multiple Doses of FG 4592 on the Pharmacokinetics of Warfarin in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02252731
- Acronym / sponsor ID
- 1517-CL-0509
- Conditions
- Pharmacokinetics of FG-4592, Healthy Subjects
- Keywords
- Phase I, FG-4592, Warfarin, Pharmacokinetics, Pharmacodynamics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Astellas Pharma Europe B.V.Industry (pharma, biotech, devices)
- Collaborators
- Kyntra Bio
- Study start
- Sep 2013
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 30 Sep 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.
This study will determine the effect of multiple doses of FG-4592 on the pharmacokinetics (PK) of a single dose of warfarin. It will evaluate the safety and tolerability of warfarin alone and in combination with multiple doses of FG-4592, and will evaluate the effect of multiple doses of FG-4592 on the pharmacodynamics (PD) of warfarin.
Detailed description
The study consists of 2 periods, separated by a washout period (a minimum of 14 days after warfarin dosing on Day 1, Period 1). Screening takes place from Day -22 to Day -2.
Subjects are admitted to the clinical unit on Day -1 of Period 1. On Day 1 of the first period, subjects receive a single oral dose of warfarin. After completion of all assessments on Day 8, subjects are discharged from the clinical unit on the condition that there are no medical reasons for a prolonged stay. They return to the clinical unit on Day -1 of the second period, after the washout period.
In Period 2, the subjects receive multiple doses of FG 4592. On Day 7 of Period 2, FG 4592 is given concomitantly with warfarin. After completion of all assessments on Day 16 of Period 2, subjects are discharged from the clinic on the condition that there are no medical reasons for a prolonged stay. The subjects return for an End of Study Visit (ESV) 5 to 9 days after the last assessment of Period 2 (or after early withdrawal).
Safety assessments are performed throughout the study. Blood and urine samples are collected for PK and PD assessments.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| warfarin and FG-4592 | Experimental | Drug: Warfarin, Drug: FG-4592Single dose of warfarin and Multiple doses of FG-4592 in combination with a single dose of warfarin |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control.
- Male subject must not donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.
- Female subject must be either of non-childbearing potential or, if of childbearing potential, must have a negative pregnancy test at screening and Day -1 and must use two forms of birth control.
- Female subject must not donate ova starting at screening and throughout the study period and for 28 days after the final study drug administration.
Key exclusion criteria (3 listed)
- Subject has a known or suspected hypersensitivity to FG 4592, warfarin, or any components of the formulations used.
- Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (non-cutaneous) infection within 1 week prior to admission to the clinical unit [Day -1].
- Subject is lactose intolerant.
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 |
|---|---|---|
| WarfarinAlso: Coumadin®Oral | Drug | warfarin and FG-4592 |
| FG-4592Also: ASP1517,, roxadustatOral | Drug | warfarin and FG-4592 |
Primary outcome
PK of S-warfarin and R-warfarin in plasma measured by area under the curve from the time of dosing extrapolated to time infinity (AUCinf)
Time frame: Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)
PK of S-warfarin and R-warfarin in plasma measured by maximum concentration (Cmax)
Time frame: Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)
5 secondary outcomes
PK profile of S-warfarin and R-warfarin in plasma
Time frame: Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)
PK profile of FG-4592 in plasma
Time frame: Period 2 (Day 1 to Day 15)
PK profile of FG-4592 in urine
Time frame: Period 2 (Day 7 to Day 8)
Pharmacodynamics profile of warfarin in plasma
Time frame: Period 1 Day 1 to to ESV (5 to 9 days after the last protocol defined assessment of Period 2 (or after early withdrawal))
Safety profile
Time frame: Screening (Day -22 to Day -2) to ESV (5 to 9 days after the last protocol defined assessment of Period 2 (or after early withdrawal))
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 30 Sep 2014.
- Derived from this study: PubMed 26947173Groenendaal-van de Meent D, den Adel M, Rijnders S, Krebs-Brown A, Kerbusch V, Golor G, Schaddelee M. The Hypoxia-inducible Factor Prolyl-Hydroxylase Inhibitor Roxadustat (FG-4592) and Warfarin in Healthy Volunteers: A Pharmacokinetic and Pharmacodynamic Drug-Drug Interaction Study. Clin Ther. 2016 Apr;38(4):918-28. doi: 10.1016/j.clinthera.2016.02.010. Epub 2016 Mar 4.
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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.
Study Physician 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 Warfarin and FG-4592 in people with Pharmacokinetics of FG-4592 and Healthy Subjects, run by Astellas Pharma Europe B.V. at 1 site in Germany.
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 4 inclusion and 3 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 30 Sep 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 Germany. 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?
PK of S-warfarin and R-warfarin in plasma measured by area under the curve from the time of dosing extrapolated to time infinity (AUCinf) (time frame: Period 1 (Day 1 to Day 8); Period 2 (Day 7 to Day 16)). 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?
On the ClinicalTrials.gov record for NCT02252731, which also lists 1 linked publication.
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 30 Sep 2014.