A Study to Evaluate the Effect of Fluconazole and Itraconazole on Erdafitinib Pharmacokinetics in Healthy Adult Participants

NCT03135106 | Completed Phase 1

• 3 other identifiers: CR1082992017-000117-2342756493EDI1007
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the effect of multiple doses of fluconazole (an inhibitor of cytochrome P450 \[CYP\] 2C9 and CYP3A) and itraconazole (an inhibitor of CYP3A4 and P-glycoprotein \[P-gp\]) on the pharmacokinetics of a single 4-milligram (mg) oral dose of erdafitinib in healthy adult participants.

Conditions

Healthy

Outcome Measures

Primary Outcomes (4)

• Maximum Observed Plasma Analyte Concentration (Cmax) of Erdafitinib

  The Cmax is the maximum observed plasma analyte concentration.

  Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168, 336, 504 and 672 hours post-dose

• Area Under the Plasma Analyte Concentration-time Curve From the Time of 0 to one Week Post-doses [(AUC)0-168h] of Erdafitinib

  Area under the plasma analyte concentration-time curve from time 0 to one week post-dose (168 hours).

  Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 168 hours post-dose

• Area Under the Plasma Analyte Concentration-time Curve From Time 0 to Time of the Last Observed Quantifiable Concentration [(AUC)0-last] of Erdafitinib

  \[(AUC)0-last\] is defined as area under the plasma analyte concentration-time curve from time 0 to time of the last observed quantifiable concentration (Clast).

  Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168, 336, 504 and 672 hours post-dose

• Area Under the Analyte Concentration-Time Curve From Time 0 to Infinite Time [(AUC)0-infinity] of Erdafitinib

  \[(AUC)0-infinity\] is defined as the area under the analyte concentration-time curve from time 0 to infinite time, calculated as the sum of AUClast and Clast/lambda (z), in which Clast is the last observed quantifiable concentration and lambda (z) is the first-order rate constant associated with the terminal portion of the curve, determined as the negative slope of the terminal log-linear phase of the drug concentration-time curve.

  Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168, 336, 504 and 672 hours post-dose

Secondary Outcomes (1)

• Percentage of Participants With Adverse Events (AEs) as a Measure of Safety

  From screening to end of study (approximately up to 61 days)

Study Arms (3)

Treatment A: Erdafitinib alone

EXPERIMENTAL

Participants will receive single 4 milligram (mg) oral dose of erdafitinib on Day 1 in a fasted state.

Drug: Erdafitinib

Treatment B: Erdafitinib + Fluconazole

EXPERIMENTAL

Participants will receive 400 mg fluconazole once daily orally from Day 1 to Day 11 in a fasted state and on Day 5, a single 4-mg oral dose of erdafitinib will be administered 30+/-10 minutes after the intake of 400 mg fluconazole dose.

Drug: Erdafitinib; Drug: Fluconazole

Treatment C: Erdafitinib + Itraconazole

EXPERIMENTAL

Participants will receive 200 mg itraconazole once daily orally from Day 1 to Day 11 and on Day 5, a single 4-mg oral dose of erdafitinib will be administered 30+/-10 minutes after the intake of 200 mg itraconazole dose.

Drug: Erdafitinib; Drug: Itraconazole

Interventions

Erdafitinib DRUG

A single 4-mg of erdafitinib tablet will be administered on Day 1 in Treatment A and on Day 5 in Treatment B and C.

Also known as: G-024

Treatment A: Erdafitinib alone; Treatment B: Erdafitinib + Fluconazole; Treatment C: Erdafitinib + Itraconazole

Fluconazole DRUG

A 400-mg fluconazole orally (4\*100 mg capsules) will be administered from Day 1 to Day 11.

Treatment B: Erdafitinib + Fluconazole

Itraconazole DRUG

A 200-mg itraconazole orally (2\*100 mg capsules) will be administered from Day 1 to Day 11.

Treatment C: Erdafitinib + Itraconazole

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Be healthy on the basis of physical examination, medical history, vital signs, and triplicate 12-lead electrocardiogram (ECG) performed at screening
• Be healthy on the basis of clinical laboratory tests performed at screening. If the results of the serum chemistry panel, other specific tests, blood coagulation or hematology are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the participant's source documents and initialed by the investigator. Healthy participants should be characterized by the following genotype regarding CYP2C9: \*1/\*1 (wild type), \*1/\*2 or \*1/\*3
• If a woman, must have a negative serum beta-human chorionic gonadotropin (hCG) pregnancy test at screening and on Day 1
• If a woman, must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 3 months after the last study drug administration
• If a man who is sexually active, must agree to use a condom; and if a man who is sexually active with a woman of childbearing potential and who has not had a vasectomy, must agree to use a condom in combination with an adequate contraception method as deemed appropriate by the investigator, example, partner using effective contraception (defined as hormonal contraception \[pill, patch, injection\], intrauterine device, surgical sterilization) during the study and not to donate sperm for 5 months after the last study drug administration

You may not qualify if:

• History of or current clinically significant medical illness including cardiac arrhythmias or other cardiac disease, hematologic disease, coagulation disorders, lipid abnormalities, significant pulmonary disease, including bronchospastic respiratory disease, diabetes mellitus, hepatic or renal insufficiency, thyroid disease, neurologic or psychiatric disease, infection, or any other illness that the investigator considers should exclude the participant or that could interfere with the interpretation of the study results
• History or current evidence of ophthalmic disorder, such as central serous retinopathy (CSR) or retinal vein occlusion, active wet age related macular degeneration, diabetic retinopathy with macular edema, uncontrolled glaucoma, corneal pathology such as keratitis, keratoconjunctivitis, keratopathy, corneal abrasion, inflammation, or ulceration
• Clinically significant abnormal values for hematology or clinical chemistry at screening as deemed appropriate by the investigator
• Clinically significant abnormal physical examination, vital signs, or triplicate 12-lead ECG at screening as deemed appropriate by the investigator
• Donated blood or blood products or had substantial loss of blood (more than 500 \[milliliter\]mL) within 3 months before the first study drug administration or intention to donate blood or blood products during the study

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (1)

Clinical Pharmacology Unit

Merksem, 2170, Belgium

Location

Related Publications (1)

• Poggesi I, Li LY, Jiao J, Hellemans P, Rasschaert F, de Zwart L, Snoeys J, De Meulder M, Mamidi RNVS, Ouellet D. Effect of Fluconazole and Itraconazole on the Pharmacokinetics of Erdafitinib in Healthy Adults: A Randomized, Open-Label, Drug-Drug Interaction Study. Eur J Drug Metab Pharmacokinet. 2020 Feb;45(1):101-111. doi: 10.1007/s13318-019-00581-9.

  PMID: 31673875 DERIVED

MeSH Terms

Interventions

erdafitinib; Fluconazole; Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: April 14, 2017
• First Posted: May 1, 2017
• Study Start: April 14, 2017
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: February 3, 2025

Record last verified: 2025-01

Locations

BE (1)