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Bioequivalence Study of Palbociclib Capsules in Healthy Chinese Subjects Under Fasting and Fed Conditions

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Abstract

Background and Objective

Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinase 4/6 used for the treatment of advanced breast cancer. This study compared the pharmacokinetic and safety profiles between a new generic and a branded reference formulation of palbociclib capsules in healthy Chinese subjects under fasting and fed conditions and evaluated the bioequivalence of two palbociclib products to obtain sufficient evidence for the marketing approval of the new generic drug.

Methods

A randomized, open-label, two-period crossover study was conducted in healthy Chinese volunteers under both fasting and fed conditions (30 subjects/condition). Eligible healthy subjects received a single 125-mg dose of the palbociclib test or reference formulation followed by a 14-day washout period. Serial blood samples were collected at scheduled timepoints, and plasma concentrations were determined by a validated high-performance liquid chromatography-tandem mass spectrometry method. A non-compartment method was used to calculate the main pharmacokinetic parameters, including the area under the plasma concentration–time curve (AUC) from time 0 to the time of the last measurable concentration (AUC0–t), the AUC from time 0 to infinity (AUC0–∞), the maximum plasma concentration (Cmax), the time to maximum plasma concentration, and the elimination half-life. The geometric mean ratios and the corresponding 90% confidence intervals of palbociclib were acquired for the bioequivalence analysis. Safety and tolerability were assessed by monitoring adverse events, laboratory assessments, vital signs, physical examinations, and 12-lead electrocardiograms.

Results

Under the fasting condition, the pharmacokinetic parameter values of the test formulation were similar to those of the reference formulation. The 90% confidence intervals of geometric mean ratios of the test to reference formulations were 94.35–103.82% for Cmax, 94.79–103.26% for AUC0–t, and 94.82–103.38% for AUC0–∞, which are all within the accepted bioequivalence range of 80.00–125.00%. Meanwhile, under the fed condition, the pharmacokinetic parameter values of the test formulation were also similar to those of the reference formulation. The 90% confidence intervals of geometric mean ratios of the test to reference formulations were 96.65–103.56% for Cmax, 98.06–103.61% for AUC0–t, and 97.88–103.46% for AUC0–∞, which are all within the accepted bioequivalence range of 80.00–125.00%. The test and reference products were well tolerated, and no serious adverse events occurred during the study.

Conclusions

Pharmacokinetic bioequivalence of palbociclib in healthy subjects was established between the palbociclib test formulation and the reference formulation under fasting and fed conditions according to predetermined regulatory criteria. The two formulations were safe and well tolerated.

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Acknowledgments

We thank all the subjects who participated in this study and the study staff of Wuxi People’s Hospital Affiliated with Nanjing Medical University.

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Authors and Affiliations

  1. Drug Clinical Trial Institution, Wuxi People’s Hospital Affiliated with Nanjing Medical University, Wuxi, 214023, Jiangsu, China

    Nan-nan Chu, Lin Zhang, Jiakun Wang, Xianghong Gu, Ying Ding, Kai Huang, Lin-Ling Que & Qing He

Authors
  1. Nan-nan Chu
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  2. Lin Zhang
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  3. Jiakun Wang
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  4. Xianghong Gu
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  5. Ying Ding
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  6. Kai Huang
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  7. Lin-Ling Que
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  8. Qing He
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Corresponding author

Correspondence to Qing He.

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Funding

This study was sponsored and funded by Jiangsu Haosen Pharmaceutical Group Co., Ltd.

Conflict of interest

All authors declare no financial support from any organization for the submitted work, no commercial or financial involvements that might present a conflict of interest related to the contribution, and no other activities that influenced the submitted work.

Ethics approval

The study was reviewed and approved by the independent Ethics Committee of Wuxi People’s Hospital Affiliated with Nanjing Medical University (approval number 2019LLPJ-I-47). The study was conducted following Good Clinical Practice guidelines, International Conference on Harmonization guidelines, applicable regulations governing clinical study conduct, and the ethical principles that have their origin in the Declaration of Helsinki.

Consent to participate

Written informed consent was obtained from all individual participants included in the study.

Consent for publication

Not applicable.

Availability of data and material

Basic information about the study is available at: http://www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml.

Code availability

Not applicable.

Authors’ contributions

Qing He and Nannan Chu designed the study. Nannan Chu wrote the manuscript and conducted the study with Lin Zhang, Jiakun Wang, Xianghong Gu, Ying Ding, Kai Huang, and Lin-Ling Que. Qing He reviewed and provided valuable comments on the manuscript.

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Cite this article

Chu, Nn., Zhang, L., Wang, J. et al. Bioequivalence Study of Palbociclib Capsules in Healthy Chinese Subjects Under Fasting and Fed Conditions. Clin Drug Investig 42, 53–63 (2022). https://doi.org/10.1007/s40261-021-01103-9

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  • DOI: https://doi.org/10.1007/s40261-021-01103-9

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