A Phase 3, Randomized, Double-Blind, Double-Dummy, Multicenter, Prospective Study to Assess the Efficacy and Safety of IV Eravacycline Compared with Ertapenem in Complicated Urinary Tract Infections

INTERVENTION: Product Name: eravacycline Product Code: TP‐434 Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: ERAVACYCLINE CAS Number: 1207283‐85‐9 Current Sponsor code: TP‐434 Other descriptive name: ERAVACYCLINE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 53‐ Pharmaceutical form of the placebo: Solution for infusion Route of administration of the placebo: Intravenous use Trade Name: INVANZ Pharmaceutical Form: Powder for concentrate for solution for infusion INN or Proposed INN: ERTAPENEM CAS Number: 0153832‐46‐3 Other descriptive name: ERTAPENEM Concentration unit: g gram(s) Concentration type: equal Concentration number: 1.0‐ Pharmaceutical form of the placebo: Solution for infusion Route of administration of the placebo: Intravenous use Trade Name: LEVOFLOXACIN Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: LEVOFLOXACIN CAS Number: 100986‐85‐4 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 250‐ CONDITION: Complicated Urinary Tract Infections ; MedDRA version: 19.0 Level: PT Classification code 10046571 Term: Urinary tract infection System Organ Class: 10021881 ‐ Infections and infestations Therapeutic area: Diseases [C] ‐ Bacterial Infections and Mycoses [C01] PRIMARY OUTCOME: Main Objective: The primary objective is to demonstrate that eravacycline is non‐inferior to ertapenem in microbiological outcome in the microbiological modified intent‐to‐treat (micro‐MITT) and microbiologically evaluable (ME) populations at the Test of Cure (TOC) visit.; ; For the FDA: The primary objective is to demonstrate that IV eravacycline is non‐inferior to ertapenem in responder outcome (clinical cure and microbiologic success) in the microbiological intent‐to‐treat (micro‐ITT) population at the End of IV (EOI) visit (within 1 day of the completion of IV study drug treatment) and Test of Cure (TOC) visit (defined as 14‐17 days after randomization).; Primary end point(s): The primary endpoint will be the microbiologic outcome at the TOC visit in the micro‐MITT and ME populations.; ; For the FDA: the primary endpoints of the study are the responder rates (clinical cure and microbiologic success) at the End of IV (EOI) and Test of Cure (TOC) visits in the micro‐ITT population.; ; Secondary Objective: The secondary objectives of the study are:; 1. To compare responder outcomes in the treatment arms at Day 5.; 2. To compare clinical outcomes in the treatment arms at Day 5, EOI, End of Treatment (EOT), TOC, and Follow‐up (FU) visits.; 3. To compare microbiologic outcomes in the treatment arms at Day 5, EOI, EOT, TOC and FU visits.; 4. To assess safety and tolerability of IV eravacycline administration.; 5. To explore pharmacokinetic (PK) parameters of IV eravacycline. Timepoint(s) of evaluation of this end point: End of IV (EOI) and Test of Cure (TOC) visits SECONDARY OUTCOME: Secondary end point(s): The secondary endpoints of the study are ; ‐ Responder rate at Day 5 ; ‐ Clinical outcome at Day 5, End of IV (EOI), EOT (End of Treatment), Test of Cure (TOC), and Follow‐Up (FU) ; ‐ Microbiologic outcome at Day 5, EOI, EOT, TOC, and FU Timepoint(s) of evaluation of this end point: Day 5, End of IV (EOI), EOT (End of Treatment), Test of Cure (TOC), and Follow‐Up (FU) INCLUSION CRITERIA: 1. Male and female subjects with either: a. Pyelonephritis and normal urinary tract anatomy (approximately 50% of the total population), OR b. cUTI with at least one of the following conditions associated with a risk for developing cUTI: i. Indwelling urinary catheter ii. Urinary retention (at least approximately 100 mL of residual urine after voiding) iii. History of neurogenic bladder iv. Partial obstructive uropathy (e.g., nephrolithiasis, bladder stones, and ureteral strictures) v. Azotemia of renal origin (not congestive heart failure [CHF] or volume related) such that the serum blood urea nitrogen [BUN] is elevated (> 20 mg/dL) AND the serum BUN:creatinine ratio is < 15 vi. Surgically modified or abnormal urinary tract anatomy (eg, bladder diverticula, redundant urine collection system, etc.) EXCEPT urinary tract surgery within the last 30 days (placing of stents or catheters is not considered to be surgical modification