A bioequivalence study of trifluridine/tipiracil tablets in Chinese metastatic colorectal cancer patients under fed conditions.

Purpose: Colorectal cancer (CRC) is the second most common cause of cancer death worldwide. Trifluridine (FTD) remained at higher concentrations longer when administered along with tipiracil (TPI) compared with FTD alone. Lonsurf is a combination formulation consisting of FTD and TPI. This study aimed to investigate the bioequivalence of FTD/TPI formulations in Chinese metastatic colorectal cancer (mCRC) patients.

Methods: In this phase I, randomized, open-label, single-dose, two-sequence, four-cycle crossover study in mCRC patients, the bioequivalence of 60 mg (20 mg tablet, 3 tablets) of the test formulation and the reference formulation (Lonsurf) was evaluated. Due to its high variability, the method of reference-scaled average bioequivalence (RSABE) was used to investigate the bioequivalence of the test and reference formulations.

Results: Thirty-two patients were enrolled. 78.1% of the subjects were male, and the mean (standard deviation) age was 53.9 (SD =  ± 9.0) years old. The time to reach the maximum plasma concentration (T) was almost 2.0 h post-dose. The geometric least-squares mean ratios (GMRs) (test/reference) of C and AUC for FTD were 95.3% and 102.9%, respectively, with 90% confidence intervals (CIs) for the natural log-transformed ratios of C and AUC of 90.0-100.9% and 99.9-105.9%, while the GMRs of C and AUC for TPI were 95.7% and 100.7%, respectively, with 90% CIs of 90.5-101.2% and 97.0-104.7%. In addition, the GMRs of C and AUC for FTD's major metabolite, trifluorothymine (FTY), were 94.8 (90% CI 90.3-99.5%) and 99.33 (90% CI 96.9-101.9%), respectively. These were in accord with the FDA bioequivalence definition interval of 80-125%.

Conclusion: The test and reference FTD/TPI formulations were bioequivalent in Chinese mCRC patients under fed conditions.