A Study to Investigate the Effect of Severe Renal Impairment on Gilteritinib Compared to Healthy Participants With Normal Renal Function

NCT04699877 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2215-CL-01142020-003993-32
• Study Type: interventional
• Target: 17
• Locations: 2 countries
• Sites: 4

Brief Summary

The purpose of the study was to evaluate the pharmacokinetics of a single oral dose of gilteritinib in male and female participants with severe renal impairment compared to healthy male and female participants with normal renal function. This study also evaluated safety and tolerability of a single oral dose of gilteritinib in male and female participants with severe renal impairment and healthy male and female participants with normal renal function. Part 2 of the study (mild and moderate renal impairment) was not conducted based on the final pharmacokinetic findings from part 1 (severe renal impairment).

Conditions

Renal Impaired; Gilteritinib; Normal Renal Function; Pharmacokinetics of ASP2215

Keywords

Gilteritinib

Outcome Measures

Primary Outcomes (7)

• Pharmacokinetics (PK) of gilteritinib in plasma: Area under the concentration-time curve (AUC) from the time of dosing extrapolated to time infinity (AUCinf)

  Area under the concentration-time curve from the time of dosing extrapolated to time infinity was derived from the plasma samples.

  Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)

• PK of gilteritinib in plasma: Area under the concentration-time curve from the time of dosing to the last measurable concentration (AUClast)

  Area under the concentration-time curve from the time of dosing to the last measurable concentration was derived from the plasma samples.

  Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)

• PK of gilteritinib in plasma: Maximum concentration (Cmax)

  Maximum plasma concentration of gilteritinib was derived from the plasma samples.

  Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)

• PK of gilteritinib in plasma: Apparent clearance (CL/F)

  CL/F derived from plasma samples.

  Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)

• Pk of gilteritinib in plasma: Area under the concentration-time curve from the time of dosing extrapolated to the time infinity (unbound)(AUCinf,u)

  Area under the concentration-time curve from the time of dosing extrapolated to time infinity (unbound) was derived from plasma samples.

  Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)

• PK of gilteritinib in plasma: Area under the concentration-time curve from the time of dosing to the last measurable concentration (unbound) (AUClast, u)

  Area under the concentration-time curve from the time of dosing to the last measurable concentration (unbound) was derived from plasma samples.

  Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)

• PK of gilteritinib in plasma: Maximum concentration (unbound) (Cmax,u)

  Maximum concentration of gilteritinib (unbound) was derived from plasma samples.

  Predose on day 1 and at the following postdose time points on 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24,48, 72, 96, 120, 144, 168, 192, 216, 240, 264, 288, 312 hour(s) and at the end of study (maximum: day 23)

Secondary Outcomes (1)

• Number of participants with Treatment Emergent Adverse Events (TEAEs)

  Up to Day 23

Study Arms (2)

Gilteritinib (Severe Renal Impairment)

EXPERIMENTAL

Participants with severe renal impairment received a single oral dose of 20 milligrams (mg) of gilteritinib on day 1, under fasting conditions.

Drug: Gilteritinib

Gilteritinib (Normal Renal Function)

EXPERIMENTAL

Participants with normal renal function received a single oral dose of 20 mg of gilteritinib on day 1, under fasting conditions.

Drug: Gilteritinib

Interventions

Gilteritinib DRUG

Oral

Also known as: ASP2215, XOSPATA®

Gilteritinib (Normal Renal Function); Gilteritinib (Severe Renal Impairment)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is eligible for participation in the study if all of the following apply:
• Participant has body mass index (BMI) range of 18.5 to 40.0 kg/m\^2, inclusive and weighs at least 50 kg at screening.
• Female participant is not pregnant and the following condition apply: Not a woman of childbearing potential (WOCBP)
• Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 120 days after Investigational Product (IP) administration.
• Male participant must not donate sperm during the treatment period and for 120 days after investigational product (IP) administration.
• Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 120 days after IP administration.
• Participant has renal function defined by estimated glomerular filtration rate (eGFR) using modification of diet in renal disease (MDRD) formula:
• Normal renal function with eGFR ≥ 90 mL/min per 1.73 m\^2, or
• Mild renal impairment with eGFR 60 to \<90 mL/min per 1.73 m\^2, or
• Moderate renal impairment with eGFR 30 to \<60 mL/min per 1.73 m\^2, or
• Severe renal impairment as defined by the National Kidney Foundation and by eGFR \<30 mL/min per 1.73 m\^2 and not on hemodialysis (preferably not higher than 20 mL/min per 1.73 m\^2, with at least 50% of participants required to have eGFR ≤ 20 mL/min per 1.73 m\^2).
• Participant has adequate venous access to allow collection of study-related samples.
• Participant agrees not to participate in another interventional study while participating in the present study.

You may not qualify if:

• Participant will be excluded from participation in the study if any of the following apply:
• Participant has received any investigational therapy within 28 days or 7 half-lives, whichever is longer, prior to day -1.
• Participant has any condition which makes the participant unsuitable for study participation.
• Female participant who has been pregnant within 6 months prior to screening or breastfeeding within 3 months prior to screening.
• Participant has a known or suspected hypersensitivity to gilteritinib or any components of the formulation used.
• Participant has had previous exposure with gilteritinib.
• Participant has any of the liver function tests (alkaline phosphatase \[ALP\], alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and total bilirubin \[TBL\]) ≥ 1.5 × upper limit of normal on day -1. In such a case, the assessment may be repeated once.
• Participant has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies) prior to IP administration.
• Participant has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection) or fungal (noncutaneous) infection within 1 week prior to day -1.
• Participant has a mean corrected QT interval using Fridericia's formula (QTcF) of \> 450 msec (for male and female participants) on day -1. If the mean QTcF exceeds the limits above, 1 additional triplicate 12-lead electrocardiogram (ECG) may be taken.
• Participant has a history of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to day -1.
• Participant has a history of consuming \> 14 units for male participants or \> 7 units for female participants of alcoholic beverages per week within 6 months prior to screening or has a history of alcoholism 3 months prior to screening or drug/chemical/ substance abuse within 1 year prior to screening (note: 1 unit = 12 ounces of beer, 4 ounces of wine, 1 ounce of spirits/hard liquor) or the participant tests positive for alcohol at screening or on day -1.
• Participant has used any inducer of cytochrome P450 (CYP)3A metabolism (e.g., St. John's Wort, barbiturates and rifampin) in the 3 months prior to day -1.
• Participant has had significant blood loss, donated ≥ 1 unit (450 mL) of whole blood or donated plasma within 7 days prior to day -1 and/or received a transfusion of any blood or blood products within 60 days.
• Participant has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease or a family history of long QT syndrome.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (4)

National Institute of Clinical Research

Garden Grove, California, 92844, United States

Location

Orange County Research Institute

Tustin, California, 92780, United States

Location

Orlando Clinical Research Center

Orlando, Florida, 32809, United States

Location

Site BG35901

Sofia, 1000, Bulgaria

Location

MeSH Terms

Interventions

gilteritinib

Study Officials

• Medical Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 7, 2021
• Study Start: January 28, 2021
• Primary Completion: July 18, 2022
• Study Completion: July 18, 2022
• Last Updated: November 5, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); BU (1)