1837. Safety Results from the ZEUS Study: Multi-center, Randomized, Double-Blind Phase 2/3 Study in Hospitalized Adults with Complicated Urinary Tract Infections (cUTI) Including Acute Pyelonephritis (AP) who Received Intravenous Fosfomycin (ZTI-01)
Session: Poster Abstract Session: Clinical Study with New Antibiotics and Antifungals
Saturday, October 7, 2017
Room: Poster Hall CD
Posters
  • Zavante_Poster1837_revCC.pdf (96.0 kB)
  • Background: Intravenous (IV) fosfomycin has been extensively used over four decades outside the US. ZTI-01 (fosfomycin for injection) is an injectable epoxide antibiotic with a unique mechanism of action and broad in vitro spectrum of activity, including multidrug-resistant pathogens. ZTI-01 is being developed for the treatment of complicated urinary tract infections (cUTI) and acute pyelonephritis (AP) in the US.

    Methods: ZEUS was a multicenter, randomized, double-blind Phase 2/3 trial that evaluated safety and efficacy of ZTI-01 in treating hospitalized adults with cUTI or AP vs piperacillin/tazobactam (P-T). Patients enrolled (N=465) were randomized to receive 6 g ZTI-01 as 1-hour IV infusion q8h (18 g total daily dose) or 4.5 g IV P-T as 1-hour IV infusion q8h (13.5 g total daily dose) for a fixed 7 days (up to 14 days if concurrent bacteremia); oral step-down therapy was prohibited. Safety parameters were analyzed, including adverse events (AEs), vital signs, laboratory assessments and electrocardiograms.

    Results: Most treatment emergent AEs (TEAEs) were mild, transient and did not lead to discontinuation of study drug. Serious adverse events (SAEs) and severe AEs were uncommon; no deaths were reported during the study (Table 1). The most common TEAEs were gastrointestinal (GI) in nature.

    Table 1. Adverse Events

    n (%)

    ZTI-01 (n=233)

    P-T (n=231)

    Any AEs

    99 (42.5)

    74 (32.0)

    Any TEAEs

    98 (42.1)

    74 (32.0)

    Mild

    84 (36.1)

    49 (21.2)

    Moderate

    35 (15.0)

    38 (16.5)

    Severe

    5 (2.1)

    4 (1.7)

    Drug-related TEAEs

    48 (20.6)

    32 (13.9)

    SAEs

    5 (2.1)

    6 (2.6)

    Drug-related SAE

    1 (0.4)

    1 (0.4)

    TEAEs leading to study drug discontinuation

    7 (3.0)

    6 (2.6)

    Serious TEAEs leading to study drug discontinuation

    0

    1 (0.4%)

    TEAEs ≥5%

    GI Disorders

    25 (10.7)

    17 (17.4)

    Investigations (Lab Abnormalities)

    20 (8.6)

    8 (3.5)

    Infections/Infestations

    17 (7.3)

    20 (8.7)

    Metabolism/Nutrition Disorders

    17 (7.3)

    4 (1.7)

    General Disorders/Administration Site

    14 (6.0)

    14 (6.1)

     Conclusion: ZTI-01 was well tolerated in patients with cUTI and AP. ZTI‑01, if approved in the US, would provide a new therapeutic option with a unique MOA for patients with serious Gram-negative infections.

    Louis B. Rice, MD, FIDSA1, Keith S. Kaye, MD, MPH2, Aaron Dane, MSc3, David Skarinsky, BS4, Anita Das, PhD5, Evelyn J. Ellis-Grosse, PhD4 and Paul B Eckburg, MD4, (1)Brown University, Providence, RI, (2)University of Michigan Medical School, Ann Arbor, MI, (3)DaneStat Consulting, Alderley Edge, United Kingdom, (4)Zavante Therapeutics, Inc., San Diego, CA, (5)Das Statistical Consulting, Guerneville, CA

    Disclosures:

    L. B. Rice, Zavante Therapeutics, Inc.: Scientific Advisor , Consulting fee

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

    A. Dane, Zavante Therapeutics, Inc.: Consultant , Consulting fee

    D. Skarinsky, Zavante Therapeutics, Inc.: Employee and Shareholder , Salary

    A. Das, Zavante Therapeutics, Inc.: Consultant , Consulting fee

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

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

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 4th with the exception of research findings presented at the IDWeek press conferences.