Clinical trial NCT02161796: A Study to Evaluate the Dose-proportionality and Effects of FG-4592 in Healthy Young and Elderly Male and Female Subjects
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: PK for FG-4592
Healthy Subjects
Keywords: Phase 1
FG-4592
Age/gender comparison
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: FibroGen
First posted: 2014-06-12
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility 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

Primary outcomes:
measure: 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),
timeFrame: Days 1- 4 (all periods)
measure: PK after a single dose of FG-4592 measured by maximum concentration (Cmax)
timeFrame: Days 1- 4 (all periods)
Secondary outcomes:
measure: PK of FG-4592 in plasma
timeFrame: Days 1 - 4 (all periods)
measure: PK of FG-4592 in urine
timeFrame: Days 1 - 4 (all periods)
measure: Plasma concentration of EPO, VEGF, reticulocytes and hepcidin
timeFrame: Days 1 - 4 (all periods)
measure: Safety and tolerability of a single dose FG-4592
timeFrame: Screening to ESV (5-9 days after the last assessment of Period 4 (or after early withdrawal))
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Parexel International GmbH
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Central Contact
role: STUDY_DIRECTOR
References: