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

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Abstract

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 (Tmax) was almost 2.0 h post-dose. The geometric least-squares mean ratios (GMRs) (test/reference) of Cmax and AUC0-t for FTD were 95.3% and 102.9%, respectively, with 90% confidence intervals (CIs) for the natural log-transformed ratios of Cmax and AUC0-t of 90.0–100.9% and 99.9–105.9%, while the GMRs of Cmax and AUC0-t 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 Cmax and AUC0–t 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.

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Data availability

All data generated or analyzed during this study are included in this published article.

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Acknowledgements

The study was supported by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. (Lian yun gang, Jiangsu Province, China). We thank all the patients and their families who participated in this study. We would like to thank all the investigators, site staff, and statisticians for their valuable work.

Funding

This study was funded by Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

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Authors and Affiliations

  1. Department of Oncology, The Second Affiliated Hospital of Air Force Medical University, 1 Xinsi Road, Xi’an, 710038, People’s Republic of China

    Hai-chuan Su, Jie Min, Yang Song, Li-li Liu & He-long Zhang

  2. Department of Pharmacy, The Second Affiliated Hospital of Air Force Medical University, 1 Xinsi Road, Xi’an, 710038, People’s Republic of China

    Lin-na Liu

Authors
  1. Hai-chuan Su
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  2. Jie Min
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Corresponding authors

Correspondence to Lin-na Liu or He-long Zhang.

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Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

This study was performed in accordance with the Declaration of Helsinki, the International Council for Harmonization E6 Guideline for Good Clinical Practice, and domestic regulatory guidelines of the National Medical Products Administration (NMPA) of the People’s Republic of China. This study was conducted at the Second Affiliated Hospital of Air Force Medical University (Xi’an, China), and the ethical approval protocol was obtained from the Ethics Committee of the Second Affiliated Hospital of Air Force Medical University.

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Su, Hc., Min, J., Song, Y. et al. A bioequivalence study of trifluridine/tipiracil tablets in Chinese metastatic colorectal cancer patients under fed conditions. Cancer Chemother Pharmacol 91, 167–177 (2023). https://doi.org/10.1007/s00280-022-04501-8

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  • DOI: https://doi.org/10.1007/s00280-022-04501-8

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