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

NCT ID: NCT03135106

Last Updated: 2025-02-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-14
• Study Completion Date: 2017-09-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Treatment A: Erdafitinib alone

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

Group Type: EXPERIMENTAL

Erdafitinib

Intervention Type: 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.

Treatment B: Erdafitinib + Fluconazole

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.

Group Type: EXPERIMENTAL

Erdafitinib

Intervention Type: 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.

Fluconazole

Intervention Type: DRUG

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

Treatment C: Erdafitinib + Itraconazole

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.

Group Type: EXPERIMENTAL

Erdafitinib

Intervention Type: 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.

Itraconazole

Intervention Type: DRUG

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

Interventions

Erdafitinib

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.

Intervention Type: DRUG

Fluconazole

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

Intervention Type: DRUG

Itraconazole

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

Intervention Type: DRUG

Other Intervention Names

G-024

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Clinical Pharmacology Unit

Merksem, , Belgium

Countries

Belgium

References

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.

Reference Type: DERIVED

PMID: 31673875 (View on PubMed)

Other Identifiers

2017-000117-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

42756493EDI1007

Identifier Type: OTHER

Identifier Source: secondary_id

CR108299

Identifier Type: -

Identifier Source: org_study_id