Pharmacokinetics and Bioequivalence of Apremilast Tablets in Chinese Healthy Subjects Under Fasting and Postprandial States

Abstract

Objective

This study compared the pharmacokinetics, safety and bioequivalence (BE) of generic and original apremilast tablets in healthy Chinese subjects under fasting and postprandial conditions, providing sufficient evidence for abbreviated new drug application.

Methods

A randomized, open-label, two-formulation, single-dose, two-period crossover pharmacokinetic study was performed. Thirty-two eligible healthy Chinese subjects were enrolled in fasting and postprandial studies, respectively. In each trial, subjects received a single 30-mg dose of the test or reference apremilast tablet, followed by a 7-day washout interval between periods. Serial blood samples were obtained for up to 48 h post-intake in each period, and the plasma concentrations of apremilast were determined by a validated method. The primary pharmacokinetic (PK) parameters, including the maximum plasma concentration (C_max), the areas under the plasma concentration–time curve (AUC_0-t, AUC_0-∞), were calculated using the non-compartmental method. The geometric mean ratios of the two formulations and the corresponding 90% confidence intervals (CIs) were acquired for bioequivalence analysis. The safety of both formulations was also evaluated.

Results

Under fasting and postprandial states, the PK parameters of the test drug were similar to those of the reference drug. The 90% CIs of the geometric mean ratios of the test to reference formulations were 94.09–103.44% for C_max, 94.05–103.51% for AUC_0-t, and 94.56–103.86% for AUC_0-∞ under fasting conditions, and 99.18–112.48% for C_max, 98.79–106.02% for AUC_0-t, and 98.95–105.89% for AUC_0-∞ under postprandial conditions, all of which were within the bioequivalence range of 80.00–125.00%. Both formulations were well tolerated, and no serious adverse events occurred during the study.

Conclusion

The trial confirmed that the PK parameters of the generic and original apremilast tablets were bioequivalent in healthy Chinese subjects under fasting and postprandial states, which met the predetermined regulatory standards. Both formulations were safe and well tolerated.

Clinical Trial Registration

chinaDrugtrials.org.cn, identifier CTR20191056 (July 30, 2019); chictr.org.cn, identifier ChiCTR2300076806 (October 19, 2023).

Keywords:

• apremilast
• psoriasis
• pharmacokinetics
• bioequivalence
• safety

Data Sharing Statement

Individual identified subject data is not going to be shared because of confidentiality.

Acknowledgments

The authors thank the subjects and staff who participated in the study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. WB, XS, XZ, and ZD had involved in drafting the manuscript or revising it critically for important intellectual content.

Disclosure

The authors declare that there are no conflicts of interest in this study.

Additional information

Funding

This study was funded by CSPC Ouyi Pharmaceutical Co., Ltd. (Hebei, China), the Hebei Provincial Government-funded Clinical Medicine Outstanding Talents (202218) and Hebei Medical Application Technology Tracking Project (GZ2022007).