Chaoying Hu1, Xiao Hu1, Chunhua Wang1, Zirun Zhao2, Dan Gao1, Xiaoping Chen1, Dongli Zhou3, Yue Huang3, Lin Li4, Lan Zhang5. 1. Department of Pharmacy, Phase I Clinical Trial Unit, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China. 2. Trinity College of Arts and Science, Duke University, Durham, NC, 27708, USA. 3. Merck Serono (Beijing) Pharmaceutical R&D Co., Ltd, Beijing, 100016, China. 4. Department of Pharmacy, Phase I Clinical Trial Unit, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China. linlixw@126.com. 5. Department of Pharmacy, Phase I Clinical Trial Unit, Xuanwu Hospital of Capital Medical University, Beijing, 100053, China. lanizhg@126.com.
Abstract
BACKGROUND: The pharmacokinetics of bisoprolol and amlodipine administered as a fixed-dose combination (FDC) tablet have not been sufficiently studied in healthy Chinese subjects to support a medical need for using the FDC in hypertension. OBJECTIVE: This study was conducted to compare the pharmacokinetic profiles of the bisoprolol-amlodipine FDC tablet with the bisoprolol tablet and amlodipine tablet administered concomitantly under both fasting and fed conditions. METHODS: An open-label, randomized, two-period, two-sequence crossover study was designed under both fasting and fed conditions. The plasma concentrations of bisoprolol and amlodipine were analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, and the pharmacokinetic parameters of maximum concentration (Cmax) and area under the concentration-time curve (AUC) were used to evaluate bioequivalence. RESULTS: The point estimate of geometric mean ratios of Cmax and AUC from the time of dosing to the last measurable concentration (AUCt) for bisoprolol were 97.85% and 99.46% in the fasting state, and 93.87% and 98.95% in the fed state, respectively. For amlodipine, the geometric mean ratios of Cmax and AUCt were 100.03% and 96.76% in the fasting state, and 106.56% and 103.07% in the fed state. No cases of treatment-emergent adverse events were reported during the entire study period. CONCLUSIONS: Bioequivalence was achieved for bisoprolol and amlodipine FDC under both fasting and fed conditions, and all treatments were safe and well tolerated by all study subjects. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03226275.
RCT Entities:
BACKGROUND: The pharmacokinetics of bisoprolol and amlodipine administered as a fixed-dose combination (FDC) tablet have not been sufficiently studied in healthy Chinese subjects to support a medical need for using the FDC in hypertension. OBJECTIVE: This study was conducted to compare the pharmacokinetic profiles of the bisoprolol-amlodipine FDC tablet with the bisoprolol tablet and amlodipine tablet administered concomitantly under both fasting and fed conditions. METHODS: An open-label, randomized, two-period, two-sequence crossover study was designed under both fasting and fed conditions. The plasma concentrations of bisoprolol and amlodipine were analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, and the pharmacokinetic parameters of maximum concentration (Cmax) and area under the concentration-time curve (AUC) were used to evaluate bioequivalence. RESULTS: The point estimate of geometric mean ratios of Cmax and AUC from the time of dosing to the last measurable concentration (AUCt) for bisoprolol were 97.85% and 99.46% in the fasting state, and 93.87% and 98.95% in the fed state, respectively. For amlodipine, the geometric mean ratios of Cmax and AUCt were 100.03% and 96.76% in the fasting state, and 106.56% and 103.07% in the fed state. No cases of treatment-emergent adverse events were reported during the entire study period. CONCLUSIONS: Bioequivalence was achieved for bisoprolol and amlodipine FDC under both fasting and fed conditions, and all treatments were safe and well tolerated by all study subjects. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03226275.