Pharmacokinetics of Aztreonam-Avibactam After Single- and Multiple-Dose Administration: A Phase 1, Open-Label Study in Healthy Chinese Participants and Ethnic Comparison with Non-Chinese Participants.

Combined treatment with aztreonam (an established intravenous antibiotic) and avibactam (a β-lactamase inhibitor) has the potential to address the unmet need for safe and effective agents to combat infections caused by Gram-negative bacteria producing metallo β-lactamases (MBLs). Aztreonam-avibactam may also address other problematic β-lactamases, such as extended-spectrum β-lactamases and serine carbapenemases, which may be co-expressed with MBLs and contribute to a multidrug-resistant phenotype. Based on completion of two Phase 3 trials, aztreonam-avibactam was approved in Europe (2024), the United States and China (2025). This Phase 1 open-label study assessed the pharmacokinetics, safety, and tolerability of aztreonam-avibactam in healthy Chinese participants after single- and multiple-dose administration (doses equivalent to those evaluated in Phase 3 aztreonam-avibactam trials), with a fixed 3:1 ratio. Pharmacokinetics, safety, and tolerability characteristics of aztreonam and avibactam were consistent with previous knowledge, with no clinically significant differences in exposures between Chinese and non-Chinese participants. Based on population pharmacokinetic modeling which incorporated data from the aztreonam-avibactam Phase 1-3 trials, predicted aztreonam and avibactam exposures at steady state for Phase 3 participants in China and non-China (rest-of-world) regions were numerically similar. These findings indicate that aztreonam-avibactam is well tolerated in healthy Chinese adults and support the use of the approved dose regimen by EMA for Chinese patient populations.