Clinical Trial: Safety and Efficacy of ZTI-01 (IV Fosfomycin) vs Piperacillin/Tazobactam for Treatment cUTI/AP Infections

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Randomized, Double-Blind, Comparative Study to Evaluate the Safety and Efficacy of ZTI-01 vs Piperacillin/Tazobactam in the Treatment of cUTI/AP Infection in Hospitalized Adults

Brief Summary: The purpose of the study is to demonstrate the safety and efficacy of ZTI-01 (IV fosfomycin) as non-inferior to piperacillin/tazobactam in overall success (clinical cure and microbiologic eradication) for the treatment of hospitalized patients with complicated urinary tract infections (cUTI) or acute pyelonephritis (AP).

Detailed Summary: This is a multi-center, randomized, double-blind, parallel-group study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of ZTI-01 (IV fosfomycin) compared to piperacillin/tazobactam in the treatment of hospitalized adults with cUTI or AP. Diagnosed and prescreened hospitalized patients will be randomized 1:1 to receive one of two intravenous treatments: 6 g ZTI-01 three times daily (18g total daily dose) or 4.5 g piperacillin/tazobactam three times daily (13.5g total daily dose) for 7 calendar days, with option to extend treatment up to 14 days in patients with positive blood culture at pretreatment. Patients will participate in the study for approximately 26 days. Urine cultures will be obtained and organisms quantified for qualified patients at baseline, during treatment, at end of treatment (EOT), at test of cure (TOC) and late follow up visits (LFU). Blood cultures will be obtained at baseline and repeated if positive throughout the study. Safety and efficacy evaluations will include vital signs, labs, physical exams, ECG and overall response as evaluated by the Investigator. Pharmacokinetic samples will be obtained (sparse sampling) for all patients.
Sponsor: Zavante Therapeutics

Current Primary Outcome: Proportion of patients with an overall success (clinical cure and microbiologic eradication) in m-MITT population [ Time Frame: TOC Visit (Day 19) ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Proportion of patients with a response of clinical cure in various protocol populations [ Time Frame: TOC Visit (Day 19) ]
  • Proportion of patients with a response of microbiologic eradication [ Time Frame: TOC Visit (Day 19) ]
  • Maximum Plasma Concentration [Cmax] of ZTI-01 [ Time Frame: Prior to the first dose of study medication on Day 1 (1 sample pre-dose) and at four additional time points post-dose on Days 3, 4 or 5 (sparse sampling) ]
    Population PK Modeling FDA guidance 1999
  • Area under the curve [AUC] for ZTI-01 [ Time Frame: Prior to the first dose of study medication on Day 1 (1 sample pre-dose) and at four additional time points post-dose on Days 3, 4 or 5 (sparse sampling) ]
    Population PK Modeling FDA guidance 1999


Original Secondary Outcome: Same as current

Information By: Zavante Therapeutics

Dates:
Date Received: April 13, 2016
Date Started: April 2016
Date Completion: February 2017
Last Updated: January 12, 2017
Last Verified: January 2017