Phase 1, randomized, double-blind, placebo-controlled, ascending single- and multiple-dose study of the safety, tolerability, and pharmacokinetics of intravenous xeruborbactam (QPX7728) in healthy adult subjects
María Patricia Hernández-Mitre, Steven C. Wallis, Jeffery S. Loutit, David C. Griffith, Jason A. Roberts
Patty Hernández-Mitre and colleagues have published the first-in-human Phase 1 trial of the novel dual-targeting β-lactamase inhibitor xeruborbactam (QPX7728) in Antimicrobial Agents and Chemotherapy.
This randomized, double-blind, placebo-controlled study in healthy adults assessed the safety, tolerability, and pharmacokinetics of intravenous xeruborbactam given as single and multiple ascending doses.
Key findings include:
- Predictable pharmacokinetics with dose-dependent increases in exposure.
- Renal elimination as the primary clearance pathway, with consistent urinary recovery (≈70–85%).
- Protein binding that was concentration-dependent, leading to dose proportionality for unbound (active) drug but not for total concentrations.
- Evidence of accumulation during repeated 8-hourly dosing, consistent with a ~30 h half-life.
- Well tolerated up to 1,000 mg daily for 7–10 days, with no serious or life-threatening adverse events; mild transient ALT elevations were the most common laboratory finding.
This work provides the first clinical data on xeruborbactam, supporting its further development as a partner for β-lactam antibiotics to treat infections caused by multidrug-resistant Gram-negative bacteria.
