Efficacy and safety of ceftazidime-avibactam in combination with metronidazole in Japanese patients with complicated intra-abdominal infection: A phase 3, multicentre, open-label study.

BACKGROUND

This phase 3 open-label study evaluated the efficacy and safety of ceftazidime-avibactam in Japanese patients with complicated intra-abdominal infections (cIAIs).

METHODS

Hospitalised adults with cIAI received ceftazidime-avibactam + metronidazole for 5-14 days. The primary efficacy endpoint was clinical cure at the test-of-cure (TOC) visit in the clinically evaluable (CE) analysis set. Efficacy was evaluated against a pre-defined point estimate criterion of ≥78 %. Microbiological responses, safety and pharmacokinetics were assessed as secondary objectives.

RESULTS

Sixty patients were enrolled at 27 Japanese study sites; 59 (mean age 57 years, 42 % female) were included in the modified intent-to-treat (MITT) analysis set. The most common baseline pathogens (microbiological MITT analysis set; n = 42) were Escherichia coli (n = 31; 74 %), Pseudomonas aeruginosa (n = 6; 14 %) and Klebsiella pneumoniae (n = 5; 12 %); all were susceptible to ceftazidime-avibactam. In the CE analysis set (n = 40), 36 patients (90.0 %; 95 % confidence interval: 76.3, 97.2) achieved clinical cure at TOC. Favourable per-pathogen microbiological responses at TOC were >90 % for common Gram-negative pathogens, including E. coli, K. pneumoniae, and P. aeruginosa. Adverse events were generally mild; the most common were constipation (12 %), diarrhoea (12 %), and insomnia (10 %). Pharmacokinetic observations of ceftazidime and avibactam were consistent with previous reports.

CONCLUSION

The proportion of patients with clinical cure at TOC was greater than the pre-defined threshold of 78.0 %. These findings in Japanese patients are consistent with multi-regional phase 3 non-inferiority trials demonstrating the efficacy and safety of ceftazidime-avibactam in patients with cIAIs.

CLINICALTRIALS GOV IDENTIFIER: NCT04927312.