The effects of contezolid (MRX-I, an oxazolidinone antibacterial agent) on cardiac repolarization were evaluated retrospectively using a population modeling approach in a Phase I study incorporating single ascending dose, multiple ascending dose, and food effect assessments. Linear mixed effect models were used to assess the relationships between MRX-I plasma concentrations and QT/QTc/∆QTc (baseline-adjusted), in which different correction methods for heart rate have been included. The upper bound of the one-sided 95% confidence interval (CI) for predicted ∆∆QTc was < 10 ms (ms) at therapeutic doses of MRX-I. Model performance/suitability was determined using diagnostic evaluations, which indicated rationality of one-stage concentration-QT model, as well as C-QT model suggested by Garnett et al. The finding demonstrated that MRX-I may have no clinical effects on the QT interval. Concentration-QT model may be an alternative to conventional thorough QT studies.

中文翻译：

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来自早期临床研究的ECG数据的浓度-响应模型，用于评估恶唑烷酮抗菌药康替利德（MRX-1）的QT延长风险。

在第一阶段研究中，采用人群建模方法回顾性评估了contezolid（MRX-1，恶唑烷酮类抗菌剂）对心脏复极的影响，该研究纳入了单次上升剂量，多次上升剂量和食物效果评估。线性混合效应模型用于评估MRX-1血浆浓度与QT / QTc / ∆QTc（经基线调整）之间的关系，其中包括了不同的心率校正方法。在MRX-1的治疗剂量下，预测的∆QTc的单侧95％置信区间（CI）的上限为<10 ms（ms）。使用诊断评估确定模型的性能/适用性，这表明一阶段浓度-QT模型以及Garnett等人建议的C-QT模型的合理性。该发现表明MRX-1可能对QT间隔没有临床影响。浓度-QT模型可以替代常规的全面QT研究。