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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Erdafitinib; Drug: Fluconazole; Drug: Itraconazole

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Merksem, Belgium, 2170
    • Clinical Pharmacology Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment A: Erdafitinib alone; Participants will receive single 4 milligram (mg) oral dose of erdafitinib on Day 1 in a fasted state.	Drug: 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.; Other Names: G-024
Experimental: 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.	Drug: 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.; Other Names: G-024; Drug: Fluconazole; A 400-mg fluconazole orally (4*100 mg capsules) will be administered from Day 1 to Day 11.
Experimental: 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.	Drug: 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.; Other Names: G-024; Drug: Itraconazole; A 200-mg itraconazole orally (2*100 mg capsules) will be administered from Day 1 to Day 11.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AEs) as a Measure of Safety	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	From screening to end of study (approximately up to 61 days)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2017
• Primary Completion (Actual): September 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: April 14, 2017
• First Submitted That Met QC Criteria: April 28, 2017
• First Posted (Actual): May 1, 2017

Study Record Updates

• Last Update Posted (Actual): September 25, 2017
• Last Update Submitted That Met QC Criteria: September 20, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Itraconazole; Fluconazole
• Other Study ID Numbers: CR108299; 2017-000117-23 (EudraCT Number); 42756493EDI1007 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No