1367. Clinical Cure in Secondary Efficacy Populations in Patients with Complicated Urinary Tract Infection Treated with ZTI-01 (fosfomycin for injection): Findings from the ZEUS Trial
Session: Poster Abstract Session: Novel Agents
Friday, October 5, 2018
Room: S Poster Hall
Posters
  • IDWeek CONTEPO_1367.pdf (477.3 kB)
  • Background: ZTI-01 (fosfomycin for injection) is an investigational epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has a broad spectrum of in vitro activity, including multidrug-resistant Gram-negative pathogens, and is being developed for the treatment of patients with complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States.

    Methods: ZEUS was a multicenter, double-blind Phase 2/3 trial in hospitalized adults with cUTI and AP to evaluate safety and efficacy. Randomized patients received 6 g ZTI-01 q8h or 4.5 g IV piperacillin/tazobactam (PIP-TAZ) q8h for 7 days; patients with baseline bacteremia could receive up to 14 days; study continued to late follow-up (LFU, 26 +/-2 days). Oral step-down therapy was prohibited. ZTI-01 met the primary endpoint of non-inferiority to PIP-TAZ. Secondary objectives included comparing clinical cure rates (assessed by investigator) in the modified intent-to-treat (MITT), microbiologic MITT (m-MITT), clinical evaluable (CE), and microbiologic evaluable (ME) populations at test-of-cure (TOC, Day 19 +/-2 days).

    Results: There were 464 patients randomized who received study drug. In all populations, clinical cure rates at TOC were high and similar between treatment groups (>90%) (Table).

    Conclusion: These results demonstrate consistent efficacy in multiple secondary efficacy populations for patients with cUTI and AP who were treated with either ZTI-01 or PIP-TAZ. If approved by FDA, ZTI-01 may provide a new IV option with a differentiated MOA for patients in the US with serious Gram-negative infections.

    Table. Clinical Response at TOC

    Population

    ZTI-01

    PIP-TAZ

    n (%)

    n (%)

    Difference (%)

    95% CI

    MITT

    233

    231

    Cure

    211 (90.6)

    212 (91.8)

    -1.2

    (-6.8, 4.4)

    Failure

    11 (4.7)

    16 (6.9)

    Indeterminate

    11 (4.7)

    3 (1.3)

    m-MITT

    184

    178

    Cure

    167 (90.8)

    163 (91.6)

    -0.8

    (-7.2, 5.6)

    Failure

    9 (4.9)

    12 (6.7)

    Indeterminate

    8 (4.3)

    3 (1.7)

    CE

    199

    196

    Cure

    188 (94.5)

    182 (92.9)

    1.6

    (-3.7, 6.9)

    Failure

    11 (5.5)

    14 (7.1)

    ME

    155

    145

    Cure

    148 (95.5)

    135 (93.1)

    2.4

    (-3.5, 8.3)

    Failure

    7 (4.5)

    10 (6.9)

    95% confidence intervals (CIs, 2-sided) were computed using a continuity-corrected Z­statistic.

    Keith Kaye, MD, MPH1, Louis B. Rice, MD, FIDSA2, Viktor Stus, MD, PhD3, Olexsiy Sagan, MD4, Elena Fedosiuk, MD5, Anita Das, PhD6, David Skarinksy, BS7, Paul B. Eckburg, M.D.7, Kristina Manvelian, MS7 and Evelyn J. Ellis-Grosse, PhD7, (1)Department of Internal Medicine, Division of Infectious Diseases, University of Michigan Medical School, Ann Arbor, MI, (2)Brown University, Providence, RI, (3)Municipal Institution Dnipropetrovsk Medical Academy of MOH of Ukraine, Dnipropetrovsk, Ukraine, (4)Department of Urology, Communal Institution Zaporizhzhia Regional Clinical Hospital, Zaporizhzhia, Ukraine, (5)Brest Regional Hospital, Brest, Belarus, (6)Das Statistical Consulting, Guerneville, CA, (7)Zavante Therapeutics, Inc., San Diego, CA

    Disclosures:

    K. Kaye, Zavante Therapeutics, Inc.: Scientific Advisor , Consulting fee .

    L. B. Rice, Zavante Therapeutics, Inc.: Scientific Advisor , 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. Skarinksy, Zavante Therapeutics, Inc.,: Employee and Shareholder , Salary .

    P. B. Eckburg, Zavante Therapeutics, Inc.,: Consultant and Shareholder , Consulting fee .

    K. Manvelian, Zavante Therapeutics, Inc.: Employee and Shareholder , Salary .

    E. J. Ellis-Grosse, Zavante Therapeutics, Inc.,: Employee and Shareholder , Salary .

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