Safety and Efficacy Study of Cefepime-AAI101 in the Treatment of Complicated Urinary Tract Infections

Inclusion Criteria

1. Male or female patients >18 years of age at the time of signing of informed consent;

2. Expectation that the patient's cUTI or AP will require hospitalisation and initial
treatment with at least 7 days of intravenous (i.v.) antibiotics;

3. Female patients who are no longer of childbearing potential

4. Female patients of childbearing potential must have a negative urine and/or serum
pregnancy test (serum β-human chorionic gonadotropin) within 1 day prior to study
entry;

5. Male patients, female patients receiving hormone replacement therapy (HRT), and female
patients of childbearing potential must agree to use highly effective contraception
methods

6. Pyuria, defined as: a. White blood cell count >10 cells/mm3 in unspun urine or ≥10
cells/high power field in spun urine sediment; or b. Urinalysis/dipstick analysis
positive for leukocyte esterase;

7. Clinical signs and/or symptoms of cUTI or AP

8. Have a baseline urine culture specimen obtained within 48 hours prior to randomization

9. Expectation, in the judgment of the Investigator, that any implanted urinary
instrumentation (e.g., nephrostomy tubes, ureteric stents, etc.) will be surgically
removed or replaced before or within 24 hours after randomisation, unless removal or
replacement is considered unsafe or contraindicated.

Exclusion Criteria

1. Known urine culture with Gram-positive primary pathogen at ≥105 colony-forming units
(CFU)/mL (not contaminant) or suspected Gram-positive pathogen by Gram staining (Note:
Gram staining is optional);

2. History of significant hypersensitivity or allergic reaction to cefepime,
piperacillin/tazobactam, any of the excipients used in the respective formulations,
any beta-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, or
monobactams), or any beta-lactamase inhibitors (e.g., tazobactam, sulbactam, or
clavulanic acid);

3. In the opinion of the Investigator, the patient is considered unlikely to survive the
approximately 6-week study period;

4. Weight >180 kg;

5. Concurrent infection that would interfere with evaluation of response to the study
antibiotics;

6. Need for or receipt of concomitant systemic antimicrobial agents after signing of
informed consent, in addition to those designated in the study-treatment groups, with
the exception of a single oral dose of any antifungal treatment for vaginal
candidiasis;

7. Receipt of potentially effective systemic antibacterial therapy for a continuous
duration of > 24 hours during the previous 72 hours before the study-qualifying
baseline urine is obtained;

8. Complicated urinary tract infection (UTI) known at study entry to be caused by
pathogens resistant to the study antibiotics;

9. Likely to require the use of an antibiotic for cUTI or AP prophylaxis during the
patient's participation in the study;

10. Intractable UTI at baseline that the Investigator anticipates would require >14 days
of study drug therapy;

11. Complete, permanent obstruction of the urinary tract that is not anticipated to be
medically or surgically relieved during i.v. study therapy and before End of Treatment
(EOT);

12. Gross hematuria requiring intervention other than administration of study drug or
removal or exchange of a urinary catheter;

13. Presence of any known or suspected disease or condition that, in the opinion of the
Investigator, may confound the assessment of efficacy.

14. Suspected or confirmed acute bacterial prostatitis, orchitis, epididymitis, or chronic
bacterial prostatitis as determined by history and/or physical examination;

15. Impairment of renal function with estimated glomerular filtration rate <30 mL/min/1.73
m2 calculated by the 4-variable Modification of Diet in Renal Disease study equation,

16. Urinary tract surgery within 7 days prior to randomisation or urinary tract surgery
planned during the study period (except surgery required to relieve an obstruction or
place a stent or nephrostomy prior to EOT);

17. Any condition or circumstance that, in the opinion of the Investigator, would
compromise the safety of the patient or the quality of study data;

18. Any rapidly progressing disease or immediately life-threatening illness, including
acute hepatic failure and respiratory failure;

19. Presence of sepsis, producing life-threatening organ dysfunction

20. A QT interval corrected using Fridericia's formula >450 msec;

21. Immunocompromising condition, including known history of acquired immune deficiency
syndrome or known recent CD4 count <200/mm3, hematological malignancy, or bone marrow
transplantation; or immunosuppressive therapy including cancer chemotherapy,
medications for prevention of organ transplantation rejection, or the administration
of corticosteroids ≥20 mg of prednisone or equivalent per day administered
continuously for >14 days prior to randomisation;

22. One or more of the following laboratory abnormalities in baseline specimens obtained
at Screening: aspartate aminotransferase, alanine aminotransferase, alkaline
phosphatase, or total bilirubin level >3 × upper limit of normal, or current
clinically significant liver disease, including any form of known liver cirrhosis;

23. One or more of the following laboratory abnormalities at Screening: platelet count
<50,000/μL, absolute neutrophil count <1,000/mm3, or hemoglobin <8 g/dL;