Meng-Na Wang1, Hai-Tao Yu2, Ya-Qian Li1, Yun Zeng1, Shuang Yang3, Guo-Ping Yang1,3,4,5,6, Qi Pei6, Jie Huang1,3. 1. Center for Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People's Republic of China. 2. Research and Development Center, Nanjing Chia Tai Tianqing Pharmaceutical Co., Ltd., Nanjing 210038, People's Republic of China. 3. Research Center of Drug Clinical Evaluation of Central South University, Changsha, Hunan 410013, People's Republic of China. 4. XiangYa School of Pharmaceutical Sciences, Central South University, Changsha, Hunan 410013, People's Republic of China. 5. National-Local Joint Engineering Laboratory of Drug Clinical Evaluation Technology, Changsha, Hunan 410013, People's Republic of China. 6. Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, People's Republic of China.
Abstract
OBJECTIVES: This study was conducted to evaluate the bioequivalence (BE) of a generic form of obeticholic acid (OCA) and OcalivaTM 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 SWR of lnCmax, lnAUC0-t and lnAUC0-∞ 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 AUC0-t of the test drug, the AUC0-t, and AUC0-∞ 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.
OBJECTIVES: This study was conducted to evaluate the bioequivalence (BE) of a generic form of obeticholic acid (OCA) and OcalivaTM 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 SWR of lnCmax, lnAUC0-t and lnAUC0-∞ 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 AUC0-t of the test drug, the AUC0-t, and AUC0-∞ 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.
Authors: Gideon M Hirschfield; Jessica K Dyson; Graeme J M Alexander; Michael H Chapman; Jane Collier; Stefan Hübscher; Imran Patanwala; Stephen P Pereira; Collette Thain; Douglas Thorburn; Dina Tiniakos; Martine Walmsley; George Webster; David E J Jones Journal: Gut Date: 2018-03-28 Impact factor: 23.059
Authors: Preeti Pathak; Cen Xie; Robert G Nichols; Jessica M Ferrell; Shannon Boehme; Kristopher W Krausz; Andrew D Patterson; Frank J Gonzalez; John Y L Chiang Journal: Hepatology Date: 2018-05-21 Impact factor: 17.425
Authors: Kris V Kowdley; Raj Vuppalanchi; Cynthia Levy; Annarosa Floreani; Pietro Andreone; Nicholas F LaRusso; Roshan Shrestha; James Trotter; David Goldberg; Simon Rushbrook; Gideon M Hirschfield; Thomas Schiano; Yuying Jin; Richard Pencek; Leigh MacConell; David Shapiro; Christopher L Bowlus Journal: J Hepatol Date: 2020-03-10 Impact factor: 25.083