A Multi-Dose, Double-Blind, Double-Dummy, Active- Control, Randomized Clinical (Phase II) Study of Two Dosing Regimens of Finafloxacin for the Treatment of cUTI and/or Acute Pyelonephritis Requiring Hospitalisation.
Overview
- Phase
- Phase 2
- Intervention
- Finafloxacin 800 mg tablets once daily
- Conditions
- Urinary Tract Infections
- Sponsor
- MerLion Pharmaceuticals GmbH
- Enrollment
- 225
- Locations
- 1
- Primary Endpoint
- Number of Participants With Clinical and Microbiological Response
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief 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.
Detailed Description
Fluoroquinolones are frequently prescribed for complicated Urinary Tract Infections (cUTI) and pyelonephritis, due to their activity against cUTI pathogens and high levels of excretion in the urine following oral and i.v. administration. However, many currently prescribed fluoroquinolones exhibit reduced antibacterial activity at low pH, which suggests reduced activity in infected urinary tracts.
Investigators
Eligibility Criteria
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.
Exclusion Criteria
- •Uncomplicated cystitis in females.
- •Failed previous antibiotic treatment within the last 4 weeks due to culture confirmed fluoroquinolone resistant pathogens.
- •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).
- •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.
- •Indwelling urinary catheters expected to remain in place after therapy has been completed.
- •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.
- •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.
- •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.
- •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.
- •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.
Arms & Interventions
Finafloxacin 5 days
Intervention: Finafloxacin 800 mg i.v. once daily and Ciprofloxacin placebo i.v. twice daily. Finafloxacin 800 mg tablets once daily and Ciprofloxacin placebo oral twice daily Finafloxacin verum (i.v. and oral) for a total of 5 days.
Intervention: Finafloxacin 800 mg tablets once daily
Finafloxacin 5 days
Intervention: Finafloxacin 800 mg i.v. once daily and Ciprofloxacin placebo i.v. twice daily. Finafloxacin 800 mg tablets once daily and Ciprofloxacin placebo oral twice daily Finafloxacin verum (i.v. and oral) for a total of 5 days.
Intervention: Finafloxacin 800 mg i.v. once daily
Finafloxacin 5 days
Intervention: Finafloxacin 800 mg i.v. once daily and Ciprofloxacin placebo i.v. twice daily. Finafloxacin 800 mg tablets once daily and Ciprofloxacin placebo oral twice daily Finafloxacin verum (i.v. and oral) for a total of 5 days.
Intervention: Ciprofloxacin placebo i.v. twice daily
Finafloxacin 5 days
Intervention: Finafloxacin 800 mg i.v. once daily and Ciprofloxacin placebo i.v. twice daily. Finafloxacin 800 mg tablets once daily and Ciprofloxacin placebo oral twice daily Finafloxacin verum (i.v. and oral) for a total of 5 days.
Intervention: Ciprofloxacin placebo oral twice daily
Finafloxacin 10 days
Intervention: Finafloxacin 800 mg i.v. once daily and Ciprofloxacin placebo i.v. twice daily. Finafloxacin 800 mg tablets once daily and Ciprofloxacin placebo oral twice daily Finafloxacin verum (i.v. and oral) for a total of 10 days.
Intervention: Ciprofloxacin placebo oral twice daily
Finafloxacin 10 days
Intervention: Finafloxacin 800 mg i.v. once daily and Ciprofloxacin placebo i.v. twice daily. Finafloxacin 800 mg tablets once daily and Ciprofloxacin placebo oral twice daily Finafloxacin verum (i.v. and oral) for a total of 10 days.
Intervention: Finafloxacin 800 mg i.v. once daily
Finafloxacin 10 days
Intervention: Finafloxacin 800 mg i.v. once daily and Ciprofloxacin placebo i.v. twice daily. Finafloxacin 800 mg tablets once daily and Ciprofloxacin placebo oral twice daily Finafloxacin verum (i.v. and oral) for a total of 10 days.
Intervention: Finafloxacin 800 mg tablets once daily
Finafloxacin 10 days
Intervention: Finafloxacin 800 mg i.v. once daily and Ciprofloxacin placebo i.v. twice daily. Finafloxacin 800 mg tablets once daily and Ciprofloxacin placebo oral twice daily Finafloxacin verum (i.v. and oral) for a total of 10 days.
Intervention: Ciprofloxacin placebo i.v. twice daily
Ciprofloxacin 10 days
Intervention: Ciprofloxacin 400 mg i.v. twice daily and Finafloxacin placebo i.v. once daily Ciprofloxacin 500 mg oral twice daily and Finafloxacin placebo tablets once daily Ciprofloxacin (i.v. and oral) for a total of 10 days.
Intervention: Finafloxacin placebo i.v. once daily
Ciprofloxacin 10 days
Intervention: Ciprofloxacin 400 mg i.v. twice daily and Finafloxacin placebo i.v. once daily Ciprofloxacin 500 mg oral twice daily and Finafloxacin placebo tablets once daily Ciprofloxacin (i.v. and oral) for a total of 10 days.
Intervention: Finafloxacin placebo tablets once daily
Ciprofloxacin 10 days
Intervention: Ciprofloxacin 400 mg i.v. twice daily and Finafloxacin placebo i.v. once daily Ciprofloxacin 500 mg oral twice daily and Finafloxacin placebo tablets once daily Ciprofloxacin (i.v. and oral) for a total of 10 days.
Intervention: Ciprofloxacin 400 mg i.v. twice daily
Ciprofloxacin 10 days
Intervention: Ciprofloxacin 400 mg i.v. twice daily and Finafloxacin placebo i.v. once daily Ciprofloxacin 500 mg oral twice daily and Finafloxacin placebo tablets once daily Ciprofloxacin (i.v. and oral) for a total of 10 days.
Intervention: Ciprofloxacin 500 mg oral twice daily
Outcomes
Primary Outcomes
Number of Participants With Clinical and Microbiological Response
Time Frame: Day 17
The primary endpoint of this study is the clinical and microbiological response of patients with cUTI or pyelonephritis to treatment with finafloxacin for 5 days versus finafloxacin for 10 days versus ciprofloxacin for 10 days as a reference comparator at the Test of Cure (ToC) visit (Day 17) in the microbiological intent-to-treat population (micro-ITT population). Clinical response is defined as resolution of the symptoms of cUTI present at trial entry and no new symptoms developed. Microbiological response is defined as elimination or reduction of study entry pathogens to ≤ 10e3 CFU/mL on urine culture. The clinical and microbiological response will be assessed for each group on Day 17 and will be compared between the three groups to assess the efficacy in each group.
Secondary Outcomes
- The Safety and Tolerability of Multiple Doses of Finafloxacin: Number of Participants Who Discontinued Due to TEAE(Screening to day 24)
- Number of Participants With Clinical and Microbiological Response at the On Therapy (OT) Visit (Day 3).(Day 3)
- Number of Participants With Clinical and Microbiological Response at the End of Therapy (EoT) Visit (Day 10).(Day 10)
- Number of Participants With Clinical and Microbiological Response at the End of Study (EoS) Visit (Day 24).(Day 24)
- The Safety and Tolerability of Multiple Doses of Finafloxacin: Number of Treatment-emergent Adverse Events(Screening to Day 24)