BACKGROUND AND OBJECTIVES: Erdafitinib, an oral selective pan-fibroblast growth 
factor receptor (FGFR) kinase inhibitor, is primarily metabolized by cytochrome 
P450 (CYP) 2C9 and 3A4. The aim of this phase 1 study was to assess the 
pharmacokinetics and safety of erdafitinib in healthy participants when 
coadministered with fluconazole (moderate CYP2C9 and CYP3A inhibitor), and 
itraconazole (a strong CYP3A4 and P-glycoprotein inhibitor). The effect of 
CYP2C9 genotype variants (*1/*1, *1/*2, *1/*3) on the pharmacokinetics of 
erdafitinib was also investigated.
METHODS: In this open-label, parallel-group, single-center study, eligible 
healthy adults were randomized by CYP2C9 genotype to receive Treatment A (single 
oral dose of erdafitinib 4 mg) on day 1, Treatment B (fluconazole 400 mg/day 
orally) on days 1-11, or Treatment C (itraconazole 200 mg/day orally) on days 
1-11. Healthy adults randomized to Treatment B and C received a single oral 4-mg 
dose of erdafitinib on day 5. The pharmacokinetic parameters, including mean 
maximum plasma concentration (Cmax), area under the curve (AUC) from time 0 to 
168 h (AUC168h), AUC from time 0 to the last quantifiable concentration 
(AUClast), and AUC from time 0 to infinity (AUC∞) were calculated from 
individual plasma concentration-time data using standard non-compartmental 
methods.
RESULTS: Coadministration of erdafitinib with fluconazole increased Cmax of 
erdafitinib by approximately 21%, AUC168h by 38%, AUClast by 49%, and AUC∞ by 
48% while coadministration with itraconazole resulted in no change in 
erdafitinib Cmax and increased AUC168h by 20%, AUClast by 33% and AUC∞ by 34%. 
Erdafitinib exposure was comparable between participants with CYP2C9 *1/*2 or 
*1/*3 and with wild-type CYP2C9 genotype. The ratio of total amount of 
erdafitinib excreted in the urine (inhibited to non-inhibited) was 1.09, the 
ratio of total amount of excreted metabolite M6 was 1.21, and the ratio of the 
metabolite to parent ratio in the urine was 1.11, when coadministration of 
erdafitinib with itraconazole was compared with single-dose erdafitinib. 
Treatment-emergent adverse events (TEAEs) were generally Grade 1 or 2 in 
severity; the most commonly reported TEAE was headache. No safety concerns were 
identified with single-dose erdafitinib when administered alone and in 
combination with fluconazole or itraconazole in healthy adults.
CONCLUSION: Coadministration of fluconazole or itraconazole or other 
moderate/strong CYP2C9 or CYP3A4 inhibitors may increase exposure to erdafitinib 
in healthy adults and thus may warrant erdafitinib dose reduction or use of 
alternative concomitant medications with no or minimal CYP2C9 or CYP3A4 
inhibition potential.
TRIAL REGISTRATION: ClinicalTrials.gov identifier number: NCT03135106.