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Peer-reviewedCC BY 4.0Antimicrobial Agents and Chemotherapy

A Phase I, randomized, double-blind, placebo-controlled, dose escalation study to evaluate the safety, tolerability, and pharmacokinetics of intravenous ertapenem and zidebactam in combination (WCK 6777) in healthy adult subjects

  • T. P. Lodise1
  • R. Chavan2
  • A. Patel2
  • R. Yeole2
  • S. Bhagwat2
  • M. Patel2
  • G. A. Saviolakis3
  • M. Kankam4
  • K. Gu5
  • V. Ghazaryan5
  • A. Jaunarajs6
  • S. R. Fairfax6
2 more authors
  • H. Howell6
  • R. A. Bonomo7,8,9,10,11,12,13
13 affiliations
  1. 1Albany College of Pharmacy and Health Sciences, Albany, New York, USA
  2. 2Wockhardt Research Centre, Chhatrapati Sambhaji Nagar, Maharashtra, India
  3. 3DynPort Vaccine Company, Frederick, Maryland, USA
  4. 4Altasciences Clinical Kansas, Inc., Overland Park, Kansas, USA
  5. 5Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, USA
  6. 6The Emmes Company, LLC, Rockville, Maryland, USA
  7. 7Infectious Diseases Section, Medical and Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center (GRECC), VA Northeast Ohio Healthcare System, Cleveland, Ohio, USA
  8. 8Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA
  9. 9Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio, USA
  10. 10Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA
  11. 11Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio, USA
  12. 12Department of Proteomics and Bioinformatics, Case Western Reserve University, Cleveland, Ohio, USA
  13. 13Case VA CARES, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio, USA
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Abstract

WCK 6777 is a novel once-daily β-lactam enhancer combination comprising ertapenem (ERT) and zidebactam (ZID), designed to expand ERT activity against multidrug-resistant gram-negative Enterobacterales, including serine- and metallo-β-lactamase producers. This first-in-human, randomized, double-blind, placebo-controlled Phase 1 study evaluated the safety, tolerability, and pharmacokinetics (PK) of WCK 6777 and its individual components following once-daily intravenous administration for 7 days in healthy adults. In total, 54 participants were enrolled, of whom 52 received ERT alone (2 or 3 g), ZID alone (2 or 3 g), WCK 6777 (ERT + ZID at 1 + 1, 2 + 2, or 3 + 3 g), or placebo. Safety assessments included adverse events, clinical laboratory testing, vital signs, and electrocardiography. Plasma and urine PK of total and unbound ERT and ZID were characterized using noncompartmental methods. WCK 6777 was safe and well tolerated at all dose levels, with no deaths, serious adverse events, or treatment discontinuations. Adverse events were predominantly mild or moderate and were most commonly infusion-site reactions. Both ERT and ZID exhibited predictable, time-independent PK. Ertapenem exhibited a biphasic disposition with a terminal half-life supportive of once-daily dosing, whereas ZID displayed linear PK across the evaluated dose range. Plasma exposure, clearance, protein binding, and renal excretion were comparable between monotherapy and combination regimens, indicating no clinically meaningful PK interaction. Both drugs were eliminated predominantly unchanged in urine. In summary, WCK 6777 demonstrated a favorable safety profile and predictable PK following once-daily administration, supporting further clinical development, including evaluation in Phase II/III efficacy studies and potential application in outpatient parenteral antimicrobial therapy.

CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT05645757.

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Cite

BibTeXRIS
BibTeX
@article{lodise2026phase,
  title = {{A Phase I, randomized, double-blind, placebo-controlled, dose escalation study to evaluate the safety, tolerability, and pharmacokinetics of intravenous ertapenem and zidebactam in combination (WCK 6777) in healthy adult subjects}},
  author = {T. P. Lodise and R. Chavan and A. Patel and R. Yeole and S. Bhagwat and M. Patel and G. A. Saviolakis and M. Kankam and K. Gu and V. Ghazaryan and A. Jaunarajs and S. R. Fairfax and H. Howell and R. A. Bonomo},
  journal = {Antimicrobial Agents and Chemotherapy},
  year = {2026},
  month = sep,
  doi = {10.1128/aac.00390-26},
  url = {https://doi.org/10.1128/aac.00390-26},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - A Phase I, randomized, double-blind, placebo-controlled, dose escalation study to evaluate the safety, tolerability, and pharmacokinetics of intravenous ertapenem and zidebactam in combination (WCK 6777) in healthy adult subjects
AU  - T. P. Lodise
AU  - R. Chavan
AU  - A. Patel
AU  - R. Yeole
AU  - S. Bhagwat
AU  - M. Patel
AU  - G. A. Saviolakis
AU  - M. Kankam
AU  - K. Gu
AU  - V. Ghazaryan
AU  - A. Jaunarajs
AU  - S. R. Fairfax
AU  - H. Howell
AU  - R. A. Bonomo
PY  - 2026
DA  - 2026/09/29
JO  - Antimicrobial Agents and Chemotherapy
DO  - 10.1128/aac.00390-26
UR  - https://doi.org/10.1128/aac.00390-26
AB  - WCK 6777 is a novel once-daily β-lactam enhancer combination comprising ertapenem (ERT) and zidebactam (ZID), designed to expand ERT activity against multidrug-resistant gram-negative Enterobacterales, including serine- and metallo-β-lactamase producers. This first-in-human, randomized, double-blind, placebo-controlled Phase 1 study evaluated the safety, tolerability, and pharmacokinetics (PK) of WCK 6777 and its individual components following once-daily intravenous administration for 7 days in healthy adults. In total, 54 participants were enrolled, of whom 52 received ERT alone (2 or 3 g), ZID alone (2 or 3 g), WCK 6777 (ERT + ZID at 1 + 1, 2 + 2, or 3 + 3 g), or placebo. Safety assessments included adverse events, clinical laboratory testing, vital signs, and electrocardiography. Plasma and urine PK of total and unbound ERT and ZID were characterized using noncompartmental methods. WCK 6777 was safe and well tolerated at all dose levels, with no deaths, serious adverse events, or treatment discontinuations. Adverse events were predominantly mild or moderate and were most commonly infusion-site reactions. Both ERT and ZID exhibited predictable, time-independent PK. Ertapenem exhibited a biphasic disposition with a terminal half-life supportive of once-daily dosing, whereas ZID displayed linear PK across the evaluated dose range. Plasma exposure, clearance, protein binding, and renal excretion were comparable between monotherapy and combination regimens, indicating no clinically meaningful PK interaction. Both drugs were eliminated predominantly unchanged in urine. In summary, WCK 6777 demonstrated a favorable safety profile and predictable PK following once-daily administration, supporting further clinical development, including evaluation in Phase II/III efficacy studies and potential application in outpatient parenteral antimicrobial therapy.  CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT05645757.
SN  - 0066-4804
SN  - 1098-6596
ER  -