Study to Investigate the Absorption, Metabolism and Excretion of [14C] ASP2215 in Patients With Advanced Solid Tumors

NCT02456883 | Completed Phase 1

• 1 other identifier: 2215-CL-0105
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the pharmacokinetics of 14C-labeled gilteritinib, in particular, the routes of excretion and extent of metabolism of gilteritinib following administration of a single dose of 14C-labeled gilteritinib after repeated doses of gilteritinib. This study will also evaluate the safety of repeated oral administration of gilteritinib in subjects with advanced solid tumors as well as identify the metabolic profile of gilteritinib in plasma, urine and feces after a single oral dose of 14C-labeled gilteritinib.

Conditions

Advanced Solid Tumors; Pharmacokinetics of 14C-labeled Gilteritinib

Keywords

ASP2215; 14C-labeled gilteritinib; Advanced Solid Tumors; Pharmacokinetics; gilteritinib

Outcome Measures

Primary Outcomes (22)

• Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in whole blood): AUCtau

  Area under the concentration curve over the dosing interval (AUCtau)

  Days 15 - 46

• Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in whole blood): Cmax

  Maximum concentration (Cmax)

  Days 15 - 46

• Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in whole blood): tmax

  Time of maximum concentration (tmax)

  Days 15 - 46

• Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in whole blood): t1/2

  Terminal elimination half-life (t1/2)

  Days 15 - 46

• Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in whole blood): CL/F

  Apparent body clearance after extravascular dosing (CL/F)

  Days 15 - 46

• Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in plasma): AUCtau

  Days 15 - 46

• Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in plasma): Cmax

  Days 15 - 46

• Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in plasma): tmax

  Days 15 - 46

• Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in plasma): t1/2

  Days 15 - 46

• Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity in plasma): CL/F

  Days 15 - 46

• Pharmacokinetics of 14C-labeled gilteritinib (Radioactivity ratio of whole blood/plasma concentrations): AUC

  Area under the concentration (AUC)

  Days 15 - 46

• Excretion rate of 14C-labeled gilteritinib (radioactivity in urine)

  Percent of dose excreted in urine

  Days 15 - 46

• Cumulative excretion of 14C-labeled gilteritinib (radioactivity in urine)

  Cumulative total of radioactivity excreted in urine

  Days 15 - 46

• Excretion rate of 14C-labeled gilteritinib (radioactivity in feces)

  Percent of dose excreted in feces

  Days 15 - 46

• Cumulative excretion of 14C-labeled gilteritinib (radioactivity in feces)

  Cumulative total of radioactivity excreted in feces

  Days 15 - 46

• Pharmacokinetics of gilteritinib (in plasma): AUCtau

  Days 15 - 46

• Pharmacokinetics of gilteritinib (in plasma): Cmax

  Days 15 - 46

• Pharmacokinetics of gilteritinib (in plasma): tmax

  Days 15 - 46

• Pharmacokinetics of gilteritinib (in plasma): CL/F

  Days 15 - 46

• Pharmacokinetics of gilteritinib (in urine): Aetau

  Cumulative amount of study drug excreted into urine from the time of dosing to the start of the next dosing interval (Aetau)

  Days 15 - 46

• Pharmacokinetics of gilteritinib (in urine): CLR

  Renal clearance (CLR)

  Days 15 - 46

• Pharmacokinetics of gilteritinib (in urine): AETAU%

  Percentage of study drug dose excreted into urine over the time interval between consecutive dosing (AETAU%)

  Days 15 - 46

Secondary Outcomes (1)

• Metabolite identification of gilteritinib in plasma, urine and feces

  Days 15 - 46

Study Arms (1)

gilteritinib and 14C-labeled gilteritinib

EXPERIMENTAL

Gilteritinib will be taken once daily on study days 1 through 14 and days 16 through 47. On day 15, each participant will be given a single dose of 14C-labeled gilteritinib.

Drug: gilteritinib; Drug: 14C-labeled gilteritinib

Interventions

gilteritinib DRUG

oral

Also known as: ASP2215

gilteritinib and 14C-labeled gilteritinib

14C-labeled gilteritinib DRUG

oral

gilteritinib and 14C-labeled gilteritinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject had histologically or cytologically confirmed diagnosis of advanced solid tumor (measurable or nonmeasurable disease) for which no standard therapy is available.
• Subject must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
• Subject must have a life expectancy \> 12 weeks.
• Subject must have recovered from the effects of prior systemic antineoplastic or radiation therapy(s) to ≤ Grade 1 (National Cancer Institute - Common Terminology Criteria for Adverse Events \[NCI-CTCAE\], Version 4.0) severity or to subject's baseline values, excluding alopecia.
• Subject has adequate bone marrow, renal and hepatic function at baseline, as demonstrated by the following:
• Absolute neutrophil count (ANC) ≥ 1500 cells/mm3
• Platelet count ≥ 100,000 cells/mm3
• Hemoglobin (Hb) ≥ 9 g/dL
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance \> 60 mL/min if the serum creatinine is \> 1.5 x ULN
• Total bilirubin ≤ 1.5 x ULN
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 x ULN (or \< 5 x ULN in subjects with liver metastases or hepatocellular carcinoma).
• Female subject must either:
• Be of nonchildbearing potential: postmenopausal (defined as at least 1 year without any menses) prior to screening, or documented surgically sterile
• Or, if of childbearing potential: agree not to try to become pregnant during the study and for 60 days after the final study drug administration and have a negative serum or urine pregnancy test at screening, and if heterosexually active, agree to consistently use 2 forms of birth control (at least one of which must be a barrier method) starting at screening and throughout the study period and for 60 days after final study drug administration.
• Female subject must not be breastfeeding at screening or during the study period, and for 60 days after the final study drug administration.

You may not qualify if:

• Subject has received more than 5 prior cytotoxic agent-containing regimens.
• Subject has symptomatic central nervous system (CNS) metastases or leptomeningeal involvement as assessed through medical history review and physical examination. Subject with prior brain metastases must:
• have stable neurologic status post administration of local therapy (surgery or radiation) for a minimum of 2 weeks following completion of the definitive therapy.
• be without neurologic dysfunction that would confound the evaluation of neurologic and other adverse events (AEs).
• Subject has had major surgery within 4 weeks prior to the first study dose.
• Subject has had chemotherapy within 4 weeks prior to the first study dose.
• Subject has had radiation therapy within 4 weeks prior to the first study dose.
• Subject with known hepatitis B surface antigen (HBsAg) positive status; or known or suspected active hepatitis C infection; or known human immunodeficiency virus (HIV) positive.
• Subject with malabsorption syndrome or disease or condition significantly affecting gastrointestinal function.
• Subject with significant or uncontrolled cardiac, renal, hepatic or other systemic disorders; or significant psychological conditions at baseline that in the investigator's opinion, makes the subject unsuitable for study participation.
• Subject with electrocardiogram (ECG) abnormalities on a 12-lead ECG performed within 14 days before start of the study drug that are considered by the Investigator to be clinically significant.
• Subject who has received strong or moderate inhibitors (e.g., ketoconazole or fluconazole) or inducers (e.g., rifampin or phenytoin) of cytochrome P450 (CYP)3A4 or of P-glycoprotein (P-gp), or substrates of multidrug and toxin extrusion (MATE)1 with the exception of antibiotics, antifungals, and antivirals that are used as standard of care post transplant or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject within 2 weeks prior to start of study treatment and while on study.
• Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptor, with the exception of drugs that are considered absolutely essential for the care of the subject.
• Subject has participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to the initiation of screening.
• Subject has a known history of serious hypersensitivity to ASP2215, or any component of the formulation used.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (1)

Site US10001

Cleveland, Ohio, 44195, 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 Director

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: May 29, 2015
• Study Start: March 4, 2016
• Primary Completion: May 20, 2017
• Study Completion: June 19, 2017
• Last Updated: November 5, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)