Yingzi Cui

Background and Objective Eltrombopag is an orally active thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia. The purpose of this randomized study is to evaluate the bioequivalence of test and reference eltrombopag olamine tablets in healthy Chinese subjects after consuming a low-calcium, high-fat, high-calorie breakfast. Methods This was a single-center, randomized, open-label, two-sequence, two-period crossover study. Enrolled subjects were randomly divided into two groups at a 1:1 ratio, with each group randomly receiving either the test or reference eltrombopag olamine tablets per period. The washout period was set to 14 days. The concentration of eltrombopag in plasma was quantified using validated liquid chromatography-tandem mass spectrometry. Safety assessments were conducted throughout the entire trial. Results This study ultimately included 36 healthy subjects. The geometric mean ratio for maximum plasma concentration between the test or reference eltrombopag olamine tablets was 92.68%; the geometric mean ratio for the area under the concentration–time curve from the time zero to the last measurable concentration was 97.15%; for the area under the concentration–time curve from the time zero to infinity, the geometric mean ratio was 97.30%. The geometric mean ratios and their 90% confidence intervals for the key pharmacokinetic parameters fell within the range of 80.00–125.00%. Within the safety data set of 36 subjects, adverse events were reported in nine subjects, totaling 14 occurrences. All reported adverse events were Grade 1, and no serious adverse events occurred. Conclusions These findings indicate that a single oral administration of the test eltrombopag is bioequivalent to the reference eltrombopag in healthy subjects after consuming a low-calcium, high-fat, high-calorie breakfast, with both formulations exhibiting a favorable safety profile. These results support the therapeutic interchangeability of the test formulation with the reference product, offering a reliable alternative for clinical use. Clinical Trial Registration This trial was registered at the Drug Clinical Trial Registration and Information Disclosure Platform (http://www.chinadrugtrials.org.cn, CTR20230598) and ClinicalTrials.gov (https://clinicaltrials.gov, NCT06768619).

Purpose This study aims to investigate the effect of food intake on the pharmacokinetics of TQ05105 tablets in healthy Chinese subjects, and to evaluate the safety in these subjects. Methods This Phase I clinical trial involved healthy subjects who received a single oral dose of 15 mg TQ05105, with a 2-day washout period between each period. The plasma concentrations of TQ05105 and its metabolite TQ12550 were quantified using a validated liquid chromatography-tandem mass spectrometry method. Safety assessments were conducted throughout the study. Results The study enrolled 16 healthy Chinese subjects (10 males and 6 females). Compared with the fasting condition, the postprandial administration of TQ05105 resulted in significant reductions in the maximum concentration (C_max) and area under the curve (AUC) of both TQ05105 and its metabolite TQ12550. Additionally, both the time to peak concentration (T_max) and half-life (t_1/2) of TQ05105 and its metabolite were prolonged under postprandial conditions. No serious adverse events were reported during the study. Conclusion The findings demonstrate that food intake significantly alters the pharmacokinetic parameters of TQ05105 and its metabolite TQ12550, with a notable decrease in C_max and AUC, and an increase in T_max and t_1/2. The single dose of the drug was well tolerated. Registration information This trial had registered at the Clinical Trials.gov on August 08, 2023 (https://clinicaltrials.gov, NCT05982106).

Background: Immunosuppressive drugs are routinely used to treat myasthenia gravis (MG). However, current recommendations provide limited evidence to support treatment options, leading to considerable variation in practice among healthcare specialists. Hence, we present a protocol for a systematic review and network meta-analysis (NMA) to update the evidence by comparing the efficacy and acceptability of oral immunosuppressive drugs for the treatment of MG. Methods: We will conduct a systematic review and NMA of all randomized controlled trials evaluating the following oral immunosuppressive drugs for the treatment of MG. Published studies will be searched using the following databases from inception to November 23, 2021: CENTRAL, the CINAHL, MEDLINE, Embase, PsycINFO, Web of Science, and 3 Chinese databases (Chinese Biomedical Literatures Database, CNKI, and Wan Fang database). Assessment of study eligibility and data extraction will be conducted independently by 2 reviewers. The main outcome will be a quantitative MG scoring system. We will conduct Bayesian NMA to synthesize all evidence for each outcome and obtain a comprehensive ranking of all treatments. The quality of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations framework. Results: The objective of this study was to assess the relative clinical efficacy and acceptability of first-line immunosuppressants for the treatment of MG, using a systematic review and NMA approach. Conclusion: In the absence of head-to-head trials comparing therapies, evidence from this NMA of available clinical trials will inform clinicians, patients, and families the risk-benefit profiles of different treatment options.