Pharmacokinetics, safety, and tolerability of nacubactam (OP0595) after intravenous infusion - a randomized, double-blind, placebo-controlled phase I clinical trial in healthy Chinese male subjects

Sep 30, 2026

Carbapenem-resistant Enterobacteriaceae (CRE) represent an urgent clinical challenge due to limited treatment options. This phase I randomized, double-blind, placebo-controlled trial evaluated nacubactam, a novel β-lactamase inhibitor, after single and multiple 60 ± 5-min intravenous infusions in healthy Chinese male subjects. Twenty participants received nacubactam or placebo across 1 g and 2 g dose groups to assess pharmacokinetics, safety, and tolerability. Nacubactam showed good tolerability without withdrawals, rapid peak exposure, dose-proportional pharmacokinetics, minimal accumulation, and primary renal elimination with minimal metabolite exposure.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Trial overview

Primary endpoints: pharmacokinetics and safety

Background and rationale

Trial registration and keywords

Clinical and Experimental Medicine (2026) 26:96 [https://doi.org/10.1007/s10238-025-01951-1](https://doi.org/10.1007/s10238-025-01951-1) Pharmacokinetics, safety, and tolerability of nacubactam (OP0595) after intravenous infusion: a randomized, double‑blind, placebo‑controlled phase I clinical trial in healthy Chinese male subjects Hui Qiu1 · Tingting Wu1,4 · Lei Diao2 · NiandaYu2 · Hong Chen3 · Xi Peng3 · Jie Huang1 · Jinlian Xie1 · Qian Wu1 · ShuangYang1 · XiaoyanYang1 · Long Zeng1 · Qi Pei4 · Chengxian Guo1 · Guoping Yang1,5,6 Received: 1 September 2025 / Accepted: 19 October 2025 © The Author(s) 2025 Abstract The rise of carbapenem-resistant Enterobacteriaceae (CRE) has posed a major clinical challenge, with limited treatment options. Nacubactam, a novel β-lactamase inhibitor, combined with cefepime or aztreonam, effectively supports CRE infection treatment. A randomized, double-blind, placebo-controlled clinical trial was conducted for the first time in healthy male Chinese subjects, including both single and multiple doses 60 ± 5-min intravenous infusion. Twenty participants were randomly assigned to nacubactam or placebo in two dosage groups (1 g and 2 g, 10 subjects each) to evaluate pharmacokinetics, safety, and tolerability. Nacubactam demonstrated good safety and tolerability in healthy male Chinese subjects after single and multiple doses intravenous infusion with no adverse events leading to study withdrawal. Nacubactam reached peak concentration immediately after infusion, had a short half-life, and showed dose-proportional exposure. At steady state, drug accumulation was minimal. The cumulative urinary excretion rates of nacubactam were 91.8% and 87.1% in the two dose groups, indicating primary renal elimination. Exposure to metabolites M1 and M2 was minimal. Nacubactam generally exhibited good safety and tolerability in healthy Chinese male subjects after single and multiple doses of 1 g/2 g intravenous doses. It was primarily excreted renally with minimal accumulation. Carbapenem-resistant Enterobacteriaceae (CRE) have become a growing global health threat due to limited treatment options and high morbidity and mortality. Nacubactam is a novel β-lactamase inhibitor that exerts dual inhibition on β-lactamases and penicillin-binding proteins. Its combination with ceftazidime or aztreonam is promising for treating multidrug-resistant Gram-negative bacterial infections. To support clinical development and future therapeutic applications, pharmacokinetic and safety data in different populations are crucial. In this work, we conducted a phase I randomized, double-blind, placebo-controlled trial to clinically evaluate nacubactam for the first time in healthy Chinese male subjects, demonstrating its good safety profile, dose-proportional pharmacokinetics, and mainly renal excretion. These data provide insights into the clinical application of nacubactam. Trial registration This trial was registered on the Chinese Clinical Trial Registration website, registration number ChiCTR2500103582 . Keywords Nacubactam · Carbapenem-resistant Enterobacteriaceae · Pharmacokinetics · Safety · Tolerability | Hui Qiu and Tingting Wu have contributed equally to this work. | | --- | | Guoping Yang, Chengxian Guo and Qi Pei share the last authorship. | Extended author information available on the last page of the article Introduction The widespread use of antibiotics, including carbapenems, has led to the global dissemination of various drug-resistant bacteria, such as carbapenem-resistant Enterobacteriaceae (CRE) [1–3] . Enterobacterales that were resistant to one or more carbapenem antimicrobial agents were classified as CRE [4] . Infections caused by CRE have become a significant global public health threat [5], markedly increasing the morbidity and mortality associated with bacterial infections [6] . However, the treatment options for CRE infections remain limited [7], highlighting the urgent need for resear

FAQs

What was the trial design for evaluating nacubactam?

The study used a randomized, double-blind, placebo-controlled phase I design in healthy Chinese male subjects, with single and multiple intravenous infusions.

How were participants assigned and what doses were tested?

Twenty participants were randomized to nacubactam or placebo in two dosage groups (1 g and 2 g), with 10 subjects per group.

What were the main pharmacokinetic and elimination findings?

Nacubactam reached peak concentration immediately after infusion, showed a short half-life and dose-proportional exposure, with minimal accumulation at steady state and primary renal elimination (urinary excretion 91.8% and 87.1%).

How did nacubactam perform regarding safety and tolerability?

Nacubactam demonstrated good safety and tolerability, with no adverse events leading to study withdrawal, in healthy Chinese male subjects after single and multiple doses.

Sep 30, 2026

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