Pharmacokinetics and Bioequivalence of Rasagiline Tablets in Chinese Healthy Subjects Under Fasting and Fed Conditions: An Open, Randomized, Single-Dose, Double-Cycle, Two-Sequence, Crossover Trial.

Xinghe Wang,Qi Qi,Lu Qi,Rongxia Fan,Xiaohui Feng,Haihong Bai,Yongrui Tu,Juxiang Wang,Yinjuan Li,Yongqiang Sun,Da Zhou,Ying Liu

doi:10.3389/fphar.2020.571747

Xinghe Wang, Qi Qi + Show 10 more

Open Access

https://doi.org/10.3389/fphar.2020.571747

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Abstract

Objective: This study evaluated the pharmacokinetics, safety, and bioequivalence (BE) of two formulations of rasagiline tablets in healthy Chinese subjects under fasting and fed conditions. Methods: An open, randomized, single-dose, double-cycle, two-sequence, self-crossover pharmacokinetic study in healthy Chinese subjects under fasting and high-fat postprandial conditions was performed. A total of 108 healthy subjects (36 in the fasting group and 72 in the postprandial group) were recruited. In each cycle of the study under both conditions, subjects received a single oral dose of 1 mg of a test or reference preparation of rasagiline tablets (1 mg each). A washout period of 3 days was observed. Blood samples were obtained up to 10 h post-intake. Primary endpoints were the BE of major pharmacokinetic parameters (AUC0–t and AUC0–∞) and the maximum observed serum concentration (Cmax). Secondary endpoints were safety parameters. Results: The 90% confidence interval (CI) of the geometric mean ratio (GMR) of the test drug vs. the reference drug for rasagiline was 94.16–105.35% for the AUC0–t under fasting conditions and 99.88–107.07% under postprandial conditions. The 90% CIs for the AUC0–∞ were 93.55–105.01% and 99.59–107.05% under fasting and postprandial conditions, respectively. The 90% CIs for the Cmax were 88.26–108.46% and 89.54–118.23% under fasting and postprandial conditions, respectively. The 90% CIs for the test/reference AUC ratio and Cmax ratio were within the acceptable range (0.80–1.25) for BE. In this BE study, there were no serious adverse events (AEs). Conclusion: BE between the test and the reference products was established in both fasting and postprandial conditions. The two formulations of rasagiline showed good tolerability and a similar safety profile. Clinical Trial Registration: chinaDrugtrials.org.cn, identifier CTR20181466.

Highlights

Parkinson’s disease (PD) is a progressively disabling neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra pars compacta
The 90% confidence interval (CI) for the test/reference AUC ratio and Cmax ratio were within the acceptable range (0.80–1.25) for BE
Only 1 participant withdrew due to an adverse events (AEs) of tachycardia after one administration

Summary

Introduction

Parkinson’s disease (PD) is a progressively disabling neurodegenerative disorder caused by the loss of dopaminergic neurons in the substantia nigra pars compacta. Second only to Alzheimer’s disease (AD), PD is among the most common neurodegenerative diseases in the world, affecting approximately 0.3% of the general population and 1–3% of people above 65 years of age, and the number of people suffered from PD is predicted to climb increase from 8.7 to 9.3 million by 2030 (Raza et al, 2019). The first (MAO-B) inhibitor was selegiline, with a major drawback of metabolism to (−)-amphetamine and (−)-methamphetamine. These metabolites play an “antityramine” role by inhibiting the uptake of dopamine by neurons, resulting in neurotoxicity and cardiovascular adverse effects (Avila et al.,2019; Chen and Swope, 2005; Finberg, 2020; Thébault et al, 2004). Its major metabolite is 1(R)aminoindan, which is differentiated by its distinctly nonamphetamine structural features (Thébault et al, 2004)

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