Safety, Tolerability, and Pharmacokinetics of a Novel Nitroimidazooxazole Antitubercular Agent in Healthy Adults: A Phase I Trial

一种新型硝基咪唑并噁唑类抗结核药物在健康成人中的安全性、耐受性和药代动力学:一项 I 期试验

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Abstract

This study evaluated the safety, tolerability, and pharmacokinetics of JBD0131, a novel nitroimidazooxazole antitubercular agent, in healthy adults. We previously reported JBD0131, a novel nitroimidazooxazole antitubercular agent, which overcomes drug resistance and bioavailability limitations of existing anti-tuberculosis therapies. The clinical trial was structured into three parts: an initial single ascending dose (SAD) phase under fasting conditions, a food-effect assessment, and a final multiple ascending dose (MAD) phase conducted after meals.  Among 95 enrolled participants, JBD0131 demonstrated favorable safety and tolerability across all regimens. No serious adverse events (AEs) or treatment discontinuations occurred. Treatment-emergent AE incidence was comparable to placebo without dose-dependent trends. Pharmacokinetic (PK) analysis showed that systemic exposure for JBD0131, measured by maximum plasma concentration (C (max)) and area under the plasma concentration-time curve (AUC), increased proportionally with the dose. The presence of food significantly enhanced the bioavailability and delayed the median time to reach peak concentration (T (max)) by approximately 2 h. These findings collectively demonstrate that JBD0131 has an acceptable safety profile and predictable, linear pharmacokinetics in healthy adults. The observed food effect, which boosts systemic exposure, along with the drug's linear accumulation, supports the need for further investigation to define optimal treatment regimens for future clinical development.

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