A Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety and Tolerability of ASP2215

NCT02571816 | Completed Phase 1

• 1 other identifier: 2215-CL-0106
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the single-dose pharmacokinetics of ASP2215 in subjects with mild and moderate hepatic impairment to matched healthy subjects with normal hepatic function. This study will also assess the safety and tolerability of single-dose ASP2215 in subjects with mild and moderate hepatic impairment and matched control subjects.

Conditions

Hepatic Impairment; Healthy

Keywords

Hepatic Impairment; Mild Hepatic Impairment; Healthy; ASP2215; Moderate Hepatic Impairment

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics of ASP2215 in plasma: AUCinf

  Area under the curve from time zero to infinity (AUCinf)

  Up to Day 28

• Pharmacokinetics of ASP2215 in plasma: AUClast, 480

  Area under the concentration-time curve from the time of dosing to the last measurable concentration within 480 hours postdose (AUClast,480)

  Up to Day 28

• Pharmacokinetics of ASP2215 in plasma: Cmax

  Maximum concentration (Cmax)

  Up to Day 28

Secondary Outcomes (13)

• Pharmacokinetics of ASP2215 in plasma: t1/2

  Up to Day 28

• Pharmacokinetics of ASP2215 in plasma: tmax

  Up to Day 28

• Pharmacokinetics of ASP2215 in plasma: CL/F

  Up to Day 28

• Pharmacokinetics of ASP2215 in plasma: Vz/F

  Up to Day 28

• Pharmacokinetics of ASP2215 in plasma: fu

  Up to Day 28

Study Arms (3)

ASP2215: Subjects with mild hepatic impairment

EXPERIMENTAL

Subjects with Child Pugh classification score of 5-6 (mild)

Drug: ASP2215

ASP2215: Subjects with moderate hepatic impairment

EXPERIMENTAL

Subjects with Child Pugh classification score of 7-9 (moderate)

Drug: ASP2215

ASP2215: Subjects with normal hepatic function

EXPERIMENTAL

Healthy subjects that match with respect to age, sex and body mass index (BMI)

Drug: ASP2215

Interventions

ASP2215 DRUG

oral

ASP2215: Subjects with mild hepatic impairment; ASP2215: Subjects with moderate hepatic impairment; ASP2215: Subjects with normal hepatic function

Eligibility Criteria

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

You may qualify if:

• A prospective subject is eligible for the clinical study if all of the following apply:
• Subject has a Body Mass Index (BMI) range of 18.5 - 34.0 kg/m2, inclusive and weighs at least 50 kg at screening.
• Female subject must be nonchildbearing potential;
• Postmenopausal (defined as at least 1 year without any menses) prior to screening, or
• Documented surgically sterile (at least 1 month prior to screening), and
• Female subject must have a negative pregnancy test at screening and Day -1.
• Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 45 days after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the study period and for 45 days after the final study drug administration.
• Male subject and their female spouse/partners who are of childbearing potential must be using 2 forms of highly effective birth control (1 of which must be a barrier method) starting at screening and continue throughout the study period and for 105 days after the final study drug administration.
• Male subject must not donate sperm starting at screening and throughout the study period and for 105 days after the final study drug administration.
• Subject agrees not to participate in another interventional study while participating in the present study, defined as signing the informed consent form until completion of the last study visit.
• Subject must have a Child-Pugh classification Class A (mild, 5 to 6 points) or Class B (moderate, 7 to 9 points) liver function impairment at screening.

You may not qualify if:

• A prospective subject will be excluded from participation in this clinical study if any of the following apply:
• Female subject who has been pregnant within 6 months prior to screening assessment or breastfeeding within 3 months prior to screening.
• Subject has a known or suspected hypersensitivity to ASP2215, or any components of the formulation used.
• Subject has any clinically significant history of allergic conditions (including drug allergies, asthma, eczema, or anaphylactic reactions, but excluding untreated, asymptomatic, seasonal allergies prior to study drug administration).
• Subject has/had febrile illness or symptomatic, viral, bacterial (including upper respiratory infection), or fungal (noncutaneous) infection within 1 week prior to day -1.
• Subject has a long QT interval (QTc) at baseline
• Subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmias or torsades de pointes, structural heart disease, or long corrected QT interval (QTc) syndrome or family history of long QTc syndrome
• Subjects with hypokalemia and hypomagnesemia at screening (defined as values below lower limit of normal).
• Subject has a mean pulse \< 40 or \> 90 bpm; mean systolic blood pressure (SBP) \>160 mmHg; mean diastolic blood pressure (DBP) \>100 mmHg (measurements taken in triplicate after subject has been resting in supine position for 5 minutes; pulse will be measured automatically) at day -1. If the mean blood pressure exceeds the limits above, 1 additional triplicate can be taken.
• Subject who has received the following drugs/products within 2 weeks prior to dosing:
• Strong or moderate inhibitors (e.g., ketoconazole or fluconazole) or inducers (e.g., rifampin or phenytoin) of cytochrome P450 (CYP)3A4
• Inhibitors and inducers of P-glycoprotein (P-gp)
• Substrates of multidrug and toxin extrusion (MATE) 1
• Drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5 hydroxytryptamine receptor 2B (5HT2BR)
• Subject has a history of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the clinical unit.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (1)

Site US10001

Miami, Florida, 33014, United States

Location

Related Publications (1)

• James AJ, Smith CC, Litzow M, Perl AE, Altman JK, Shepard D, Kadokura T, Souda K, Patton M, Lu Z, Liu C, Moy S, Levis MJ, Bahceci E. Pharmacokinetic Profile of Gilteritinib: A Novel FLT-3 Tyrosine Kinase Inhibitor. Clin Pharmacokinet. 2020 Oct;59(10):1273-1290. doi: 10.1007/s40262-020-00888-w.

  PMID: 32304015 DERIVED

Related Links

• Link to results on the Astellas Clinical Study Results website.

MeSH Terms

Interventions

gilteritinib

Study Officials

• Medical Monitor

  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: October 7, 2015
• First Posted: October 8, 2015
• Study Start: October 23, 2015
• Primary Completion: March 5, 2016
• Study Completion: March 5, 2016
• Last Updated: November 5, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)