目的 分析药物Ⅰ期临床试验中受试者非药物相关三酰甘油(TG)、尿酸(UA)异常的影响因素。方法 选取2021-02至2022-02在首都医科大学附属北京世纪坛医院开展的药物Ⅰ期临床试验中的96例受试者作为研究对象,于筛选入组当日(D1)、D3、D5、D15、D43、D99六个时点对受试者的血清TG、UA水平进行监测,分析以上指标异常情况及相关因素。结果 有42例(43.75%)出现血清TG水平异常,有66例(68.75%)出现血清UA水平异常,受试者在各监测时点血清TG、UA水平的差异均有统计学意义(P<0.05),受试者D3-D99的血清TG水平均高于D1水平,D5、D43、D99的血清UA水平均高于D1水平,差异均有统计学意义(P<0.05)。受试者血清TG水平异常与D1时点的血清TG水平和体质量指标(BMI)水平具有相关性(P<0.05),受试者血清UA水平异常与D1时点的血清UA水平具有相关性(P<0.05)。受试者D1时点TG、BMI水平预测TG异常的受试者工作特征曲线下面积(AUCROC)分别为0.857和0.684(P<0.05),受试者D1时点UA水平预测UA异常的AUCROC为0.845(P<0.05)。结论 药物Ⅰ期临床试验中受试者发生非药物相关TG、UA异常的比例较高,其发生风险与基线TG、UA水平、受试者的肥胖程度等因素有关。
Abstract
Objective To analyze the influential factors of non-drug related triglyceride (TG) and uric acid (UA) abnormalities in subjects in phase I clinical trials for drugs.Methods A total of 96 subjects in phase I clinical trial for drugs carried out in Beijing Shijitan Hospital Affiliated to Capital Medical University from February 2021 to February 2022 were selected as the research subjects. The serum TG and UA levels of the subjects were monitored at six time points of D1 (on the day of screening), D3, D5, D15, d43 and d99. The abnormality of TG and UA levels during their participation in the trial and their related factors were analyzed.Results There were 42 cases (43.75%) with abnormal serum TG level and 66 cases (68.75%) with abnormal serum UA level. There were significant differences in the serum TG and UA levels of subjects at each monitoring time point (P<0.05). The serum TG levels of subjects at D3-D99 were higher than those of D1, and the serum UA levels of subjects D5, D43 and D99 were higher than those of D1. The differences were statistically significant (P<0.05). The abnormality of serum TG level of the subjects was correlated with the serum TG level at D1 time point and body mass index (BMI) level (P<0.05), and the abnormality of serum UA level of the subjects was correlated with the serum UA level at D1 time point (P<0.05). The area under receiver operating characteristic curve (AUCROC) of TG at D1 time point and BMI predicting the abnormality of TG was 0.857 and 0.684 (P<0.05), respectively. AUCROC of UA level at D1 time point predicting abnormality of UA was 0.845 (P<0.05).Conclusions In the phase I clinical trial for drugs, the subjects have high proportions of non-drug related TG and UA abnormalities, and their risks are related to baseline TG and UA levels as well as the degree of obesity of the subjects.
关键词
Ⅰ期临床试验 /
非药物相关不良事件 /
三酰甘油 /
尿酸 /
相关因素
Key words
phase I clinical trial /
non-drug related adverse event /
triglyceride /
uric acid /
related factor
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基金
首都医科大学附属北京世纪坛医院院青年基金(2020q24)
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