Efficacy and Safety Study of Eravacycline Compared With Ertapenem in Participants With Complicated Urinary Tract Infections
Efficacy and Safety Study of Eravacycline Compared With Ertapenem in Participants With Complicated Urinary Tract Infections
The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of
 eravacycline compared to ertapenem in treating participants with complicated urinary tract
 infections (cUTI).
The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of
 eravacycline compared to ertapenem in treating participants with complicated urinary tract
 infections (cUTI).

 This is a phase 3, randomized, double-blind, double-dummy, multicenter, prospective study to
 assess the efficacy, safety and pharmacokinetics of eravacycline compared with ertapenem in
 the treatment of cUTI.

 Randomization will be stratified based on two criteria: (1) by primary site of infection
 (pyelonephritis and normal urinary tract anatomy vs all other diagnoses) and (2) by the
 receipt of a single dose of effective non-study antibiotics for the acute cUTI within 72
 hours prior to randomization. An enrollment cap of approximately 50% is planned for subjects
 with pyelonephritis with normal urinary tract anatomy. Also, an enrollment cap of
 approximately 20% is planned for subjects who have received a single dose of non-study
 antibiotics for the acute cUTI within 72 hours prior to randomization.

 In this study subjects will be enrolled and randomized to one of two treatment arms in a 1:1
 ratio: (i) eravacycline intravenously (IV) / levofloxacin (PO), or (ii) ertapenem (IV) /
 levofloxacin (PO).
Inclusion Criteria:

 1. Male or female participant with either:

 1. Pyelonephritis and normal urinary tract anatomy (approximately 50% of the total
 population), or

 2. cUTI with at least one of the following conditions associated with a risk for
 developing cUTI:

 -  Indwelling urinary catheter

 -  Urinary retention (at least approximately 100 milliliters (mL) of residual
 urine after voiding)

 -  History of neurogenic bladder

 -  Partial obstructive uropathy (for example, nephrolithiasis, bladder stones,
 and ureteral strictures)

 -  Azotemia of renal origin (not congestive heart failure [CHF] or volume
 related) such that the serum blood urea nitrogen [BUN] is elevated (>20
 milligrams [mg]/deciliters [dL]) and the serum BUN:creatinine ratio is <15

 -  Surgically modified or abnormal urinary tract anatomy (for example, bladder
 diverticula, redundant urine collection system) except urinary tract surgery
 within the last 30 days (placing of stents or catheters is not considered to
 be surgical modification)

 2. At least 18 years of age at time of consent

 3. Able to provide informed consent

 4. At least two of the following signs or symptoms:

 1. Chills, rigors, or warmth associated with fever or hypothermia

 2. Flank pain (pyelonephritis) or pelvic pain (cUTI)

 3. Nausea or vomiting

 4. Dysuria, urinary frequency, or urinary urgency

 5. Costo-vertebral angle tenderness on physical examination

 5. Urine specimen with evidence of pyuria

 1. Dipstick analysis positive for leukocyte esterase (where positive result is at
 least "++" as indicated on the urine dipstick provided in the laboratory kit), or

 2. ≥10 white blood cells (WBCs) per cubic millimeter, or

 3. ≥10 WBCs per high power field

 6. If male: must agree to use an effective barrier method of contraception (for example,
 condom) during the study and for 14 days following the last dose if sexually active
 with a female of childbearing potential

 7. If female, not pregnant or nursing or, if of childbearing potential: must commit to
 either use at least two medically accepted, effective methods of birth control (for
 example, condom, spermicidal gel, oral contraceptive, indwelling intrauterine device,
 hormonal implant /patch, injections, approved cervical ring) during study drug dosing
 and for 14 days following last study drug dose or practicing sexual abstinence

 Exclusion Criteria:

 1. Use of systemic antibiotics effective in cUTI within 72 hours prior to enrollment
 except under the following circumstances:

 1. Participants with suspected acute cUTI who have received a single dose of
 effective non-study antibiotics for the acute cUTI

 2. Signs and symptoms of cUTI developed while on the antibiotic for another
 indication

 2. History of an ertapenem-resistant urinary tract infection within 1 year of enrollment

 3. Likely to require >10 days of antibiotic treatment to cure the acute cUTI or likely to
 receive ongoing antibacterial drug prophylaxis prior to the Follow Up visit (21-28
 days after randomization) [for example, participants with chronic vesiculo-ureteral
 reflux]

 4. Unlikely to survive at least through the duration of the study

 5. Hypotension, systolic blood pressure ≤90 millimeters of mercury [mmHg]

 6. Complicated pyelonephritis with complete obstruction or known or suspected renal or
 perinephric abscess, emphysematous pyelonephritis, or Any condition likely to require
 surgery to achieve cure (this does not include procedure to place catheters or obtain
 diagnosis)

 7. Known or suspected urinary fungal infection

 8. Uncomplicated lower urinary tract infections

 9. Suspected or confirmed active prostatitis, or currently under treatment for
 prostatitis

 10. High risk for cUTI due to Pseudomonas (for example, history of prior cUTIs due to
 Pseudomonas, ≥20 mg once a day prednisone or equivalent steroid, and other risk
 factors as perceived by the Investigator)

 11. History of renal transplantation

 12. Presence of an ileal loop

 13. Any history of trauma to the pelvis or urinary tract occurring within 30 days of
 screening

 14. Indwelling urinary catheters present at screening which are not expected to be removed
 or replaced within 72 hours of enrollment (for example, nephrostomy tubes, stents,
 urethral and suprapubic catheters).

 15. Known concomitant human immunodeficiency virus (HIV) infection with CD4 counts below
 200 within the last six months, or an acquired immune deficiency syndrome (AIDS)
 defining diagnosis within the last six months

 16. Neutropenia (Absolute neutrophil count <1,000 polymorphonuclear leukocytes
 [PMNs]/microliters [µL])

 17. Participation in a study with an experimental drug or device within 30 days prior to
 enrollment

 18. Known or suspected hypersensitivity to tetracyclines, carbapenems, or β-lactams

 19. History of seizures

 20. Any other unstable or clinically significant concurrent medical condition (for
 example, immunosuppressive therapy, chemotherapy, class IV heart or lung disease, end
 stage renal disease, or requiring hemodialysis) that would, in the opinion of the
 Investigator, jeopardize the safety of a participant and/or their compliance with the
 protocol