Efficacy
Clinical efficacy against cUTIs
In the ASPECT-complicated urinary tract infection (cUTI) non-inferiority trial ZERBAXA demonstrated clinical efficacy vs levofloxacin
- Multinational, double-blind, randomized, noninferiority phase 3 trial with 1,068 adults hospitalized with cUTI (82% of primary end point population diagnosed with pyelonephritis) who received either ZERBAXA 1.5 g IV every 8 hours or levofloxacin 750 mg IV once daily for 7 days.
- The primary efficacy end point was composite microbiological and clinical cure response, defined as complete resolution or marked improvement of clinical symptoms and microbiological eradication (all uropathogens found at baseline at ≥105 were reduced to <104 colony-forming units/mL) at the TOC visit 7 (±2) days after the last dose of study drug. The primary efficacy analysis population was the mMITT population, which included all patients who received study medication and had at least 1 baseline uropathogen. The mMITT population consisted of 800 patients (74% female; median age of 50.5 years) with cUTI, including 656 (82%) with pyelonephritis.
- The 95% CI was based on the stratified Newcombe method.
- A treatment difference (95% Cl) of 8.5 (2.3, 14.6) was observed in the mMITT population.
- Although a statistically significant difference was observed in the ZERBAXA arm compared to the levofloxacin arm with respect to the primary end point, it was likely attributable to the 212/800 (26.5%) patients with baseline organisms non-susceptible to levofloxacin. Among patients infected with a levofloxacin-susceptible organism at baseline, the response rates were similar.
Composite microbiological and clinical cure rates in a phase 3 trial of cUTIs at TOC visit (mMITT population)
The composite cure rate in patients with concurrent bacteremia receiving ZERBAXA was 79.3% (23/29) in the mMITT population.
Clinical cure rates in a subset of ESBL-producing E. coli and K. pneumoniae isolates
- In 15% (104/687) of all isolates in both treatment arms that met prespecified criteria for beta-lactam susceptibility, genotypic testing identified certain ESBL groups (eg, TEM, SHV, CTX-M, OXA).
- Cure rates in this subset were similar to those of the overall trial results. In vitro susceptibility testing showed that some of the isolates were susceptible to ZERBAXA (MIC ≤2 mcg/mL) while some others were not susceptible (MIC >2 mcg/mL).
Definitions
ASPECT = Assessment of the Safety Profile and Efficacy of Ceftolozane and Tazobactam
CI = confidence interval
ESBL = extended-spectrum beta-lactamase
MIC = minimum inhibitory concentration
mMITT = microbiologically modified intent-to-treat
TOC = test-of-cure