Methods: The ZEUS study was a multicenter, randomized, double-blind Phase 2/3 trial designed to evaluate safety and efficacy of ZTI-01 in the treatment of hospitalized adults with cUTI or AP versus piperacillin/tazobactam (P-T). The primary endpoint of overall success was defined as clinical cure plus microbiologic eradication in the microbiologic modified intent-to-treat (m‑MITT) population at the test-of-cure (TOC) visit (Day 19). Patients enrolled (n=465) were randomized to receive 6 g ZTI-01 as a one-hour IV infusion q8h (18 g total daily dose) or 4.5 g IV P-T as a one-hour infusion q8h (13.5 g total daily dose) for a fixed 7 days, except patients with concurrent bacteremia received up to 14 days. Oral step-down therapy was prohibited.
Results: In the m-MITT population, ZTI-01 met the primary objective of non‑inferiority compared with P-T with an overall success rate of 64.7% (119/184 patients) vs 54.5% (97/178 patients), respectively; treatment difference was 10.2% (95% CI: ‑0.4, 20.8). Clinical cure rates at TOC were high and similar between treatment groups (90.8% vs 91.6%, respectively). ZTI-01 was generally well tolerated. In the safety population (n=464), treatment-emergent adverse events (TEAEs) were observed in 42.1% and 32.0% of patients in the ZTI-01 and P-T groups, respectively. Most TEAEs were mild and transient; premature discontinuation of study drug was uncommon. The most frequent clinical TEAEs were gastrointestinal in nature. Serious adverse events were uncommon (5 ZTI-01, 6 P-T), with no deaths reported during the study.
Conclusion: These results demonstrate efficacy and tolerability of ZTI-01 in patients with cUTI and AP. If approved in the US, ZTI-01 would provide a new IV therapeutic option with a unique MOA for patients with difficult to treat Gram-negative infections.
K. S. Kaye,
Zavante Therapeutics, Inc.:
A. Dane, Zavante Therapeutics, Inc.: Consultant , Consulting fee
V. Stus, Zavante Therapeutics, Inc.: Investigator , Research support
O. Sagan, Zavante Therapeutics, Inc.: Investigator , Research support
E. Fedosiuk, Zavante Therapeutics, Inc.: Investigator , Research support
A. Das, Zavante Therapeutics, Inc.: Consultant , Consulting fee
D. Skarinsky, Zavante Therapeutics, Inc.: Employee and Shareholder , Salary
P. B. Eckburg, Zavante Therapeutics, Inc.: Consultant and Shareholder , Consulting fee
E. J. Ellis-Grosse, Zavante Therapeutics: Employee and Shareholder , Salary
See more of: Poster Abstract Session