Finafloxacin for the Treatment of cUTI and/or Acute Pyelonephritis

Inclusion Criteria

• Be male or female subjects ≥ 18 years of age.
• If a female and
• subject is of childbearing potential, must have documented use of using an effective contraceptive method (such as IUD, hormonal birth control, condom and spermicidal jelly, etc.) during the study, Contraception must have been used for at least 2 months before starting the study. A documented negative urine pregnancy test must be provided and the subject must be non-lactating.
• subject is of non-childbearing potential, must be post-menopausal (i.e. has had amenorrhea for a minimum of 12 consecutive months) or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy, or hysterectomy.
• subject is truly abstinent. This is accepted as a method of contraception, but only when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• If a male, should agree to use reliable birth control methods (contraception or other barrier device) during study participation.
• Must have complicated lower urinary tract infection or acute complicated or uncomplicated pyelonephritis (cPN or uPN; see section 5.3) and must have at least two of the following acute signs and symptoms
• Chills or rigors or warmth associated with fever (e.g. oral temperature greater than 38.0 degrees Celsius ).
• Flank pain (pyelonephritis) or pelvic pain (cUTI).
• Nausea or vomiting.
• Dysuria, urinary frequency, or urinary urgency.
• Costo-vertebral angle tenderness (pyelonephritis) on physical examination.
• Provide one pre-treatment adequate urine sample (the urine sample must return a positive culture in order for the subject to remain eligible for the study) For males: midstream clean catch, for females: in-out catheterisation or midstream clean catch. The urine sample must be provided within 24 hours before the start of administration of the first dose of study drug.

A positive urine culture is defined as:

• ≥ 105 CFU/mL of one causative pathogen in the case of cUTI
• ≥ 104 CFU/mL of one causative pathogen in case of Pyelonephritis

A negative urine culture is defined as:

• < 105 CFU/mL of causative pathogen/s and/or non-target pathogens at any number of CFUs in the case of cUTI
• < 104 CFU/mL of causative pathogen/s and/or non-target pathogens at any number of CFUs in the case of Pyelonephritis Patients may be admitted to the study pending baseline urine culture results. Treatment should NOT be delayed pending urine culture results.

NOTE: Because biofilms on indwelling catheters (e.g. Foley catheters) are more likely to be present after the catheter has been in place for a period of time, samples should be collected following the placement of a new catheter. If the placement of a new catheter is contraindicated or is not feasible, specimens should be collected using aseptic techniques with the urine obtained through a properly disinfected collection port. Urine samples should never be obtained from the collection bag.

If the subject's pre-treatment culture shows the presence of a ciprofloxacin resistant pathogen the Investigator has to decide according to clinical signs and symptoms whether the subject can stay in the study.

In the event of a negative urine culture, the subject must be withdrawn from the study and switched to standard care, because the inclusion criterion is not fulfilled.

A urine culture is defined as contaminated if:

• at least one causative pathogen with ≥ 105 CFU/mL is present AND at least one non-pathogen or additional causative pathogen/s at any number of CFU/mL are present in the case of cUTI
• at least one causative pathogen with ≥ 104 CFU/mL is present AND at least one non-pathogen or additional causative pathogen/s with any number of CFU/mL in the case of pyelonephritis Subjects with contaminated urine cultures will be permitted to continue in the study