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A Study to Evaluate the Dose-proportionality and Effects of FG-4592 in Healthy Young and Elderly Male and Female Subjects

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ClinicalTrials.gov Identifier: NCT02161796
Recruitment Status : Completed
First Posted : June 12, 2014
Last Update Posted : June 12, 2014
Sponsor:
Collaborator:
FibroGen
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )

Brief Summary:

This study evaluates the concentration of FG-4592 in the blood over a certain period after the intake of different doses, and assesses the effects, the safety and the tolerability of the study drug in healthy young and elderly male and female subjects.

On Day 1 of each of 4 periods subjects receive different single doses of FG-4592 or a placebo, depending on the treatment sequence to which they are randomized. For each period the subjects remain in the clinic for 6 days (Days -2 to 4). They are discharged after all assessments are completed on Day 4 of each period, and return for an End of Study visit (ESV) between 5 and 9 days after the last assessment of Period 4.


Condition or disease Intervention/treatment Phase
PK for FG-4592 Healthy Subjects Drug: FG-4592 Drug: Placebo Phase 1

Detailed Description:

In this study eligible subjects reside in the clinic for 4 periods of 6 days (Day -2 through Day 4). Screening takes place from Day -23 through Day -3. Subjects are admitted to the clinic on Day -2 of Period 1. Within each cohort (young and elderly subjects), subjects are randomized to one of 24 treatment sequences of 4 treatment options (3 different doses of FG-4592 and placebo) and 4 periods.

On Day 1 of each period, subjects receive a single oral dose of FG-4592 or placebo followed by a 72-hour evaluation period. Subjects are discharged on Day 4, if there are no medical reasons for a prolonged stay. Each period is separated by a wash-out period of at least 10 days between dosing on Day 1 of the previous period and dosing on Day 1 of the following period. The subjects return for an end-of-study visit (ESV) 5-9 days after the last assessment of Period 4 (or after early withdrawal).

Plasma and urine samples are collected for pharmacokinetic (PK) and pharmacodynamic (PD) assessments. Safety assessments are performed throughout the study.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Basic Science
Official Title: A Phase 1, Double-blind, Randomized, Placebo-controlled, 4-way Crossover Study to Evaluate the Dose-proportionality and Pharmacokinetics of FG-4592 in Healthy Young and Elderly Male and Female Subjects
Study Start Date : September 2013
Actual Primary Completion Date : December 2013
Actual Study Completion Date : December 2013

Arm Intervention/treatment
Experimental: 1: young male subjects
3x single dose of FG-4592 and a placebo
Drug: FG-4592
Oral
Other Names:
  • ASP1517,
  • roxadustat

Drug: Placebo
Oral

Experimental: 2: young female subjects
3x single dose of FG-4592 and a placebo
Drug: FG-4592
Oral
Other Names:
  • ASP1517,
  • roxadustat

Drug: Placebo
Oral

Experimental: 3: elderly male subjects
3x single dose of FG-4592 and a placebo
Drug: FG-4592
Oral
Other Names:
  • ASP1517,
  • roxadustat

Drug: Placebo
Oral

Experimental: 4: elderly female subjects
3x single dose of FG-4592 and a placebo
Drug: FG-4592
Oral
Other Names:
  • ASP1517,
  • roxadustat

Drug: Placebo
Oral




Primary Outcome Measures :
  1. PK after a single dose of FG-4592 measured by area under the concentration-time curve from the time of dosing extrapolated to time infinity (AUCinf), [ Time Frame: Days 1- 4 (all periods) ]
  2. PK after a single dose of FG-4592 measured by maximum concentration (Cmax) [ Time Frame: Days 1- 4 (all periods) ]

Secondary Outcome Measures :
  1. PK of FG-4592 in plasma [ Time Frame: Days 1 - 4 (all periods) ]
    area under the concentration-time curve (AUC) from time point 0 to time point 24 hours (AUC0-24h), unbound AUC from time point 0 to time point 24 hours (AUC0-24h,u), AUC from the time of dosing to the last measurable concentration (Clast) (AUClast), unbound AUC from the time of dosing to Clast (AUClast,u), unbound AUC extrapolated to infinity (AUCinf,u), maximum unbound plasma concentration (Cmax,u), apparent total body clearance after extra-vascular dosing (CL/F), unbound CL/F (CLu/F), fraction unbound (fu), time interval between the time of dosing and the first measurable concentration above LOQ in Plasma (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 Vz/F (Vz,u/F)

  2. PK of FG-4592 in urine [ Time Frame: Days 1 - 4 (all periods) ]
    renal clearance (CLR), unbound CLR (CLR,u), CLR from time point 0 to 24 hours (CLR,0-24h), unbound CLR,0-24h (CLR,0-24h,u), 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 (Aelast) 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), Ae0-24h in percent of dose (Ae0-24h%)

  3. Plasma concentration of EPO, VEGF, reticulocytes and hepcidin [ Time Frame: Days 1 - 4 (all periods) ]
    EPO(erythropoietin), VEGF(vascular endothelial growth factor)

  4. Safety and tolerability of a single dose FG-4592 [ Time Frame: Screening to ESV (5-9 days after the last assessment of Period 4 (or after early withdrawal)) ]
    AEs, resting vital signs, safety laboratory tests, 12-lead safety ECG, mean heart rate per hour for 24-hours



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • YOUNG: Subject is a healthy young male or a healthy female subject aged 18 to 45 years of age inclusive
  • ELDERLY: Subject is a healthy elderly male or female subject aged 65 or above
  • Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of 2 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 -2 and must use 2 forms of birth control
  • Female subject must not be breastfeeding at screening or during the study period and for 28 days after the final study drug administration
  • Female subject must not donate ova starting at screening and throughout the study period and for 28 days after the final study drug administration

Exclusion Criteria:

  • Female subject who has been pregnant within 6 months before screening or breastfeeding within 3 months before screening
  • Subject used grapefruit, grapefruit juice (more than 3 x 200 mL) or orange marmalade (more than 3 times) in the week prior to admission to the clinic until ESV
  • The subject is a vulnerable subject

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02161796


Locations
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Germany
Parexel International GmbH
Berlin, Germany, 14050
Sponsors and Collaborators
Astellas Pharma Europe B.V.
FibroGen
Investigators
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Study Director: Central Contact Astellas Pharma Europe B.V.
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Responsible Party: Astellas Pharma Europe B.V.
ClinicalTrials.gov Identifier: NCT02161796    
Other Study ID Numbers: 1517-CL-0525
2013-001044-57 ( EudraCT Number )
First Posted: June 12, 2014    Key Record Dates
Last Update Posted: June 12, 2014
Last Verified: June 2014
Keywords provided by Astellas Pharma Inc ( Astellas Pharma Europe B.V. ):
Phase 1
FG-4592
Age/gender comparison