Overview

Finafloxacin for the Treatment of cUTI and/or Acute Pyelonephritis

Status:
Completed
Trial end date:
2015-10-01
Target enrollment:
0
Participant gender:
All
Summary
The primary objective of this study is to evaluate the microbiological and clinical outcome of treatment with finafloxacin for 5 days versus finafloxacin for 10 days versus ciprofloxacin for 10 days as a reference comparator. Finafloxacin shows increased activity in an acidic environment which is associated with indications such as uUTI and cUTI. Given the acidic pH of urine and concentration of finafloxacin excreted via the urinary tract in humans it should be proven if the finafloxacin treatments offer significant advantages over the currently available treatments for UTI.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
MerLion Pharmaceuticals GmbH
Treatments:
Ciprofloxacin
Finafloxacin
Fluoroquinolones
Criteria
Inclusion Criteria:

1. Be male or female subjects ≥ 18 years of age.

2. If a female and

1. 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.

2. 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.

3. 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.

3. If a male, should agree to use reliable birth control methods (contraception or other
barrier device) during study participation.

4. 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

1. Chills or rigors or warmth associated with fever (e.g. oral temperature greater
than 38.0 degrees Celsius ).

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

3. Nausea or vomiting.

4. Dysuria, urinary frequency, or urinary urgency.

5. Costo-vertebral angle tenderness (pyelonephritis) on physical examination.

5. 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, although this will impact on the subject's
eligibility for analysis (see section 9.3).

6. Have pyuria (i.e. a dipstick analysis positive for leukocyte esterase or at least 10
white blood cells per cubic millimetre [1 µl]).

7. Be considered ill enough to be hospitalized for at least 3 days and require initial
parenteral therapy to manage cUTI and/or acute pyelonephritis by the standard of care.

8. Provide written informed consent to participate in the study.

9. Be willing and able to comply with all study procedures and activities.

Exclusion Criteria:

1. Uncomplicated cystitis in females.

2. Failed previous antibiotic treatment within the last 4 weeks due to culture confirmed
fluoroquinolone resistant pathogens.

3. Having ileal loops, urinary diversion with bowel segments or suspected or confirmed
vesico-ureteral reflux, suspected or confirmed perinephric or intrarenal abscess (if
an abscess is suspected an ultrasound should be performed to confirm and exclude).

4. History of renal transplant any permanent complicating factors of the urinary tract
(including complete obstruction, suspected or confirmed prostatitis or epididymitis)
which cannot be effectively treated during the therapy of the infection.

5. Indwelling urinary catheters expected to remain in place after therapy has been
completed.

6. The urinary tract infection or any other concomitant bacterial infection that requires
systemic antibiotic therapy (in addition to the study treatment) at the time of
randomisation. Antibiotics with only gram-positive activity are permitted.

7. Any infection that, in the opinion of the Investigator, would be considered
intractable and likely to require more than 10 days of study drug therapy.

8. Any recent use (e.g., within 48 hours before the first dose of study medication) of an
antimicrobial therapy with a drug that has activity in the treatment of urinary tract
infection.

9. Having been exposed to any fluoroquinolone in the 30 days before Day 1 (study
enrolment), previous participation in a finafloxacin clinical trial or participation
within the last 30 days in any other clinical study in general.

10. In the 12 months before study enrolment: known uncontrolled condition of hypertension
or symptomatic hypotension, known uncontrolled cardiac arrhythmia, known ischaemic
heart disease or history of myocardial infarction, coronary artery bypass surgery or
percutaneous transluminal coronary angioplasty.

11. Significantly immunocompromised (defined as a WBC < 1000) and/or having a known
infection with human immunodeficiency virus (HIV/AIDS), any haematological malignancy,
bone marrow transplantation, or current immunosuppressive therapy (including but not
limited to cancer chemotherapy, or medications for prevention of organ transplantation
rejection).

12. Any concomitant psychiatric, neurological or behavioural disorder, including epilepsy
or other lesions of the central nervous system sufficient in the opinion of the
Investigator to prevent or compromise the subject's participation in the study.

13. Any known concomitant bacterial or fungal sexually transmitted disease with the
exception of candidiasis.

14. Having, in the opinion of the Investigator, any clinically significant serious or
unstable physical illness likely to impact on the subject's wellbeing or the conduct
and analysis of the study, including, but not limited to, acute hepatic failure,
respiratory failure, severe, persistent diarrhoea and septic shock.

15. Any surgical or medical condition which might interfere with the distribution,
metabolism or excretion of the drug, including, but not limited to moderate (including
estimated creatinine clearance of 30 - 59 mL/min) or severe impairment of renal
function (including an estimated creatinine clearance of < 30 mL/min), requirement for
peritoneal dialysis, haemodialysis or haemofiltration, or oliguria.

16. Any malignant disease or a history of malignant neoplasm requiring a treatment with
immune suppressive properties in the 6 months before baseline.

17. Known history of drug abuse.

18. Clinically abnormal haematology, biochemistry and urinalysis results at baseline
including, but not limited to:

- AST, ALT, or alkaline phosphatase level greater than 3 times the upper limit of
normal (ULN).

- Total bilirubin greater than 2 times ULN.

- WBC count less than 1000/μL, platelet count less than 50,000/μL.

- Haematocrit less than 25%.

- Creatinine clearance < 60mL/minute.

19. Any clinically significant ECG abnormality on the baseline ECG subjects at risk for
torsade de pointes arrhythmia or a history of significant or inadequately treated
cardiac disease.

20. Documented history of hypersensitivity or allergy to or known contraindication to the
use of fluoroquinolones.

21. Any history of tendon lesions or ruptures either during quinolone treatment or for any
other reason.

22. Concomitant tizanidine use.

23. Any administration of corticosteroids equivalent to or greater than 20 mg of
prednisone per day for more than 14 days before randomisation.

24. The subject, planned to be enrolled is an employee or relative of any involved study
Investigator or any involved institution including MerLion or Galenus.

25. Life expectancy of less than 3 months.

26. Women who are pregnant or nursing.

27. Any other condition that, in the opinion of the Investigator, would prevent the
subject from effectively participating in the study, place the subject at risk or
affect the assessment of efficacy and safety of the study medication.