Sulopenem Followed by Sulopenem-etzadroxil/Probenecid vs Ertapenem Followed by Cipro for Complicated UTI in Adults
Sulopenem Followed by Sulopenem-etzadroxil/Probenecid vs Ertapenem Followed by Cipro for Complicated UTI in Adults
This is a prospective, phase 3, randomized, multicenter, double-blind, double-dummy study to
 compare the efficacy and safety of sulopenem followed by sulopenem-etzadroxil/probenecid
 versus ertapenem followed by ciprofloxacin for the treatment of complicated urinary tract
 infections (cUTI) in adults.
Inclusion Criteria:

 1. Adults ≥18 years of age with more than 24 hours of urinary symptoms attributable to a
 UTI

 2. Able to provide informed consent

 3. Clinically documented pyelonephritis or complicated urinary tract infection:

 1. Pyelonephritis with normal anatomy

 2. Complicated UTI as defined by one or more of the following factors:

 i. The presence of an indwelling catheter ii. >100 mL of residual urine after voiding
 iii. Neurogenic bladder iv. Obstructive uropathy due to nephrolithiasis, tumor or
 fibrosis v. Azotemia due to intrinsic renal disease vi. Urinary retention in men
 possibly due to benign prostatic hypertrophy vii. Surgically modified or abnormal
 urinary tract anatomy

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

 1. Rigors, chills or fever/hypothermia

 2. Flank pain or pelvic pain

 3. Nausea or vomiting

 4. Dysuria, urinary frequency or urinary urgency

 5. Costovertebral angle tenderness on physical examination

 5. A mid-stream urine specimen with:

 1. a dipstick analysis positive for nitrite AND

 2. evidence of pyuria as defined by either: i. a dipstick analysis positive for
 leukocyte esterase AND/OR ii. at least 10 white blood cells per cubic millimeter
 on microscopic analysis of unspun urine AND/OR iii. White blood cell count ≥10
 cells/high-powered field in urine sediment

 Exclusion Criteria

 1. Receipt of effective antibacterial drug therapy for complicated urinary tract
 infection (cUTI) for a continuous duration of more than 24 hours during the previous
 72 hours. Patients who have objective documentation of clinical progression of cUTI
 while on antibacterial drug therapy, or patients who received antibacterial drugs for
 surgical prophylaxis and then develop cUTI, may be appropriate for enrollment.

 2. Subjects with an organism isolated from the urine within the last year known to be
 resistant to ertapenem

 3. Severe structural or functional urinary tract abnormality responsible for an
 intractable infection which in the opinion of the investigator would require > 10 days
 of therapy or post-treatment prophylaxis (eg. patients with chronic vesiculo-ureteral
 reflux).

 4. Uncomplicated UTI

 5. Patients with paraplegia/quadriplegia

 6. Hypotension with systolic blood pressure < 90 mm Hg

 7. Complicated UTI associated with complete obstruction, emphysematous pyelonephritis,
 known or suspected renal or perinephric abscess or expected to require surgical
 intervention (not placement of catheters) to achieve cure

 8. Patients with a known history of myasthenia gravis

 9. Patients who require concomitant administration of tizanidine or valproic acid

 10. Patients with a history of allergy to carbapenems or quinolones or
 amoxicillin-clavulanate or other beta-lactams, or hypersensitivity to probenecid

 11. Renal transplantation

 12. Patients requiring dialysis

 13. Acute or chronic prostatitis

 14. High risk for cUTI caused by Pseudomonas sp. (eg,. history of prior UTI due to
 Pseudomonas species, recent steroid use, others)

 15. Chronic indwelling catheters or stents

 16. Ileal loops or vesico-urethral reflux

 17. Recent trauma to the pelvis or urinary tract within the prior 30 days

 18. History of seizures

 19. Patients with a history of blood dyscrasias

 20. Patients with a history of uric acid kidney stones

 21. Patients with acute gouty attack

 22. Patients on chronic methotrexate therapy

 23. Females of child-bearing potential who are unable to take adequate contraceptive
 precautions, have a positive pregnancy test result within 24 hours of study entry, are
 otherwise known to be pregnant, or are currently breastfeeding an infant.

 24. Male subjects must agree to use of an effective barrier method of contraception during
 the study and for 14 days post treatment

 25. Patients known to have a history of liver or kidney disease or neutropenia as defined
 by the following baseline laboratory criteria:

 -  Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) > 3 X Upper
 Limit of Normal

 -  Total bilirubin > 2 X Upper Limit of Normal

 -  Neutropenia (<1000 cells/mm3)

 26. Patients participating in any other clinical study that involved the administration of
 an investigational medication

 27. Patient immunocompromised

 28. Patients unlikely to comply with the protocol

 29. Patients considered unlikely to survive the 4-week study period or has a rapidly
 progressive or terminal illness