Bioequivalence and Pharmacokinetic Profiles of Generic and Branded Obeticholic Acid in Healthy Chinese Subjects Under Fasting and Fed Conditions

Abstract

Objectives

This study was conducted to evaluate the bioequivalence (BE) of a generic form of obeticholic acid (OCA) and Ocaliva^TM under fasting and fed conditions and to determine the effects of food on the pharmacokinetic (PK) profiles of OCA in healthy Chinese subjects.

Methods

A randomized, single-dose, three-sequence, three-period, partial replicated crossover study was conducted with a 21-day washout interval between periods under fasting (n=48) and fed (n=48) conditions. Blood samples for OCA and its metabolites Glyco-OCA and Tauro-OCA were collected up to 168 hours after administration in each period. PK parameters were calculated using the non-compartmental method. Geometric mean ratios for PK parameters of the test to reference drug under fasting and fed conditions and their 90% confidence intervals were estimated. Safety evaluations were carried out all through the study.

Results

A total of 91 subjects completed the study with 45 in a fasted state and 46 receiving a high-fat diet. There were no serious or unexpected drug-related adverse events occurring during the study. There was no significant difference in the main PK parameters of the two preparations, irrespective of the fasting or fed conditions. Under fasting and fed conditions, the S_WR of lnC_max, lnAUC_0-t and lnAUC_0-∞ were 0.445, 0.370, 0.448, 0.340, 0.168, and 0.180, respectively. Thus, the average BE or the reference-scaled average BE was used to verify that the two preparations were bioequivalent under fasting and fed conditions. Compared with the fasting state, the AUC_0-t of the test drug, the AUC_0-t, and AUC_0-∞ of the reference drug were higher in the fed state.

Conclusion

The test drug and the reference drug were BE and well tolerated in Chinese healthy subjects under both fasting and fed conditions. Food-intake may cause a significant difference in the main PK parameters of the two preparations.

Keywords:

• obeticholic acid
• bioequivalence
• pharmacokinetics
• food effect

Acknowledgments

This study was supported by the Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd., the National Natural Science Foundation of China (No.81673519 and No. 81803639) and National major new drug creation project of China (No.2020ZX09201010).

Data Sharing Statement

The raw data of this study will not be shared because of agreements.

Ethical Approval

This study was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University and was performed according to the ethical standards laid down in the 1964 Declaration of Helsinki.

Informed Consent

Informed consent was obtained by all individual participants included in the study.

Author Contributions

All authors contributed to data analysis, drafting and revising of the article, gave final approval of the version to be published, agreed on the journal to which the article was submitted and agreed to be accountable for all aspects of the work.

Disclosure

Hai-Tao Yu is an employee of Nanjing Chia Tai Tianqing Pharmaceutical Co., Ltd. The authors report no other potential conflicts of interest in this work.