Clinical trial NCT03135106: A Study to Evaluate the Effect of Fluconazole and Itraconazole on Erdafitinib Pharmacokinetics in Healthy Adult Participants
Official title: A Randomized, Open-Label, Parallel Group, Drug-drug Interaction Study to Evaluate the Effect of Fluconazole and Itraconazole on the Pharmacokinetics of Erdafitinib in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-05-01
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


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

Primary outcomes:
measure: Maximum Observed Plasma Analyte Concentration (Cmax) of Erdafitinib
timeFrame: Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168, 336, 504 and 672 hours post-dose
measure: Area Under the Plasma Analyte Concentration-time Curve From the Time of 0 to one Week Post-doses [(AUC)0-168h] of Erdafitinib
timeFrame: Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96 and 168 hours post-dose
measure: Area Under the Plasma Analyte Concentration-time Curve From Time 0 to Time of the Last Observed Quantifiable Concentration [(AUC)0-last] of Erdafitinib
timeFrame: Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168, 336, 504 and 672 hours post-dose
measure: Area Under the Analyte Concentration-Time Curve From Time 0 to Infinite Time [(AUC)0-infinity] of Erdafitinib
timeFrame: Pre-dose, 1, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 168, 336, 504 and 672 hours post-dose
Secondary outcomes:
measure: Percentage of Participants With Adverse Events (AEs) as a Measure of Safety
timeFrame: From screening to end of study (approximately up to 61 days)
Other outcomes:
Locations:
city: Merksem
country: Belgium
facility: Clinical Pharmacology Unit
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.