Reexamining transaminase elevation in Phase I clinical trials: the importance of baseline and change from baseline
Reexamining transaminase elevation in Phase I clinical trials: the importance of baseline and change from baseline
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DOI：
10.1007/s00228-009-0684-x
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发表时间：
2009-10-01
影响因子：
2.9
通讯作者：
Keisu, Marianne
中科院分区：
文献类型：
--
作者：
Cai, Zhaohui;Christianson, Anastasia M.;Keisu, Marianne
本分析的目的是确定在我们的历史I期临床试验中接受安慰剂治疗的健康志愿者中转氨酶升高的患病率，并评估哪些因素与之相关。我们对来自20个I期试验的481名接受安慰剂治疗的健康志愿者的谷丙转氨酶（ALT）水平进行了回顾性分析，以正常值上限（ULN）为截止点，检查ALT升高率以及实际ALT值与基线的变化。在所有研究中，ALT的最低限值为32至72 IU/L。虽然汇总数据集的总ALT升高率（4.4%）较低，但最近的研究中ALT升高率高于早期研究。虽然基线和安慰剂治疗期间的升高率没有显著差异，但安慰剂治疗期间的ALT最高水平显著高于基线水平。此外，基线ALT水平被发现在预测安慰剂治疗期间ALT升高比人口统计学和研究设计因素更重要。在I期临床试验中，为了更可靠地解释肝脏信号，除了高于ULN的升高外，转氨酶的基线水平和基线变化也是需要检查的重要变量。
The aims of the present analysis were to determine prevalence of transaminase elevation in placebo-treated healthy volunteers in our historical phase I clinical trials and to assess which factors were associated with it.We performed a retrospective analysis of alanine transaminase (ALT) levels in 481 placebo-treated healthy volunteers from 20 phase I trials by examining ALT elevation rates using the upper limit of normal values (ULN) as the cutoff as well as changes from baseline in actual ALT values.The ULN for ALT ranged from 32 to 72 IU/L across the studies. Although the overall ALT elevation rate (4.4%) from pooled datasets was low, the elevation rates were higher in more recent studies than in earlier ones. While elevation rates at baseline and during placebo treatment did not differ significantly, ALT maximal levels during placebo treatment were significantly higher than baseline levels. Moreover, baseline ALT levels were found to be more important in predicting ALT elevation during placebo treatment than demographic and study design factors.Baseline level and changes from baseline in transaminase are important variables to examine in addition to elevation above ULN for more reliably interpreting liver signals in Phase I clinical trials.