Finafloxacin for the Treatment of cUTI and/or Acute Pyelonephritis

NCT01928433 | Completed Phase 2 Results DMC

• 2 other identifiers: FINA-0072011-006041-14
• Study Type: interventional
• Target: 225
• Locations: 1 country
• Sites: 1

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.

Conditions

Urinary Tract Infections; Acute Pyelonephritis

Keywords

Urinary Tract Infection; Pyelonephritis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Clinical and Microbiological Response

  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.

  Day 17

Secondary Outcomes (5)

• 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

• The Safety and Tolerability of Multiple Doses of Finafloxacin: Number of Participants Who Discontinued Due to TEAE

  Screening to day 24

Study Arms (3)

Finafloxacin 5 days

EXPERIMENTAL

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.

Drug: Finafloxacin 800 mg i.v. once daily; Drug: Finafloxacin 800 mg tablets once daily; Drug: Ciprofloxacin placebo i.v. twice daily; Drug: Ciprofloxacin placebo oral twice daily

Finafloxacin 10 days

EXPERIMENTAL

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.

Drug: Finafloxacin 800 mg i.v. once daily; Drug: Finafloxacin 800 mg tablets once daily; Drug: Ciprofloxacin placebo i.v. twice daily; Drug: Ciprofloxacin placebo oral twice daily

Ciprofloxacin 10 days

ACTIVE COMPARATOR

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.

Drug: Finafloxacin placebo i.v. once daily; Drug: Finafloxacin placebo tablets once daily; Drug: Ciprofloxacin 400 mg i.v. twice daily; Drug: Ciprofloxacin 500 mg oral twice daily

Interventions

Finafloxacin 800 mg i.v. once daily DRUG

Infused over 60 mins \[i.v. pump\]) for at least 3 days.

Also known as: Finafloxacin

Finafloxacin 10 days; Finafloxacin 5 days

Finafloxacin placebo i.v. once daily DRUG

Infused over 60 mins \[i.v. pump\]) for at least 3 days.

Also known as: Saline

Ciprofloxacin 10 days

Finafloxacin 800 mg tablets once daily DRUG

Administered as four 200 mg tablets

Also known as: Finafloxacin

Finafloxacin 10 days; Finafloxacin 5 days

Finafloxacin placebo tablets once daily DRUG

Administered as four tablets

Ciprofloxacin 10 days

Ciprofloxacin 400 mg i.v. twice daily DRUG

Infused over approximately 60 mins \[i.v. pump\]) for at least 3 days

Also known as: Ciprofloxacin Kabi Infusionslösung

Ciprofloxacin 10 days

Ciprofloxacin placebo i.v. twice daily DRUG

Infused over approximately 60 mins \[i.v. pump\]) for at least 3 days

Also known as: Saline

Finafloxacin 10 days; Finafloxacin 5 days

Ciprofloxacin 500 mg oral twice daily DRUG

Administered as two 250 mg capsules.

Also known as: Ciprofloxacin real 250/500/750 mg

Ciprofloxacin 10 days

Ciprofloxacin placebo oral twice daily DRUG

Administered as two capsules.

Finafloxacin 10 days; Finafloxacin 5 days

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• MerLion Pharmaceuticals GmbH: lead

Study Sites (1)

Universitätsklinikum Giessen, Klinik für Urologie, Kinderurologie und Andrologie

Giessen, 35392, Germany

Location

Related Publications (3)

• Wagenlehner F, Nowicki M, Bentley C, Luckermann M, Wohlert S, Fischer C, Vente A, Naber K, Dalhoff A. Explorative Randomized Phase II Clinical Study of the Efficacy and Safety of Finafloxacin versus Ciprofloxacin for Treatment of Complicated Urinary Tract Infections. Antimicrob Agents Chemother. 2018 Mar 27;62(4):e02317-17. doi: 10.1128/AAC.02317-17. Print 2018 Apr.

  PMID: 29339395 DERIVED

• Taubert M, Luckermann M, Vente A, Dalhoff A, Fuhr U. Population Pharmacokinetics of Finafloxacin in Healthy Volunteers and Patients with Complicated Urinary Tract Infections. Antimicrob Agents Chemother. 2018 Mar 27;62(4):e02328-17. doi: 10.1128/AAC.02328-17. Print 2018 Apr.

  PMID: 29339394 DERIVED

• Vente A, Bentley C, Luckermann M, Tambyah P, Dalhoff A. Early Clinical Assessment of the Antimicrobial Activity of Finafloxacin Compared to Ciprofloxacin in Subsets of Microbiologically Characterized Isolates. Antimicrob Agents Chemother. 2018 Mar 27;62(4):e02325-17. doi: 10.1128/AAC.02325-17. Print 2018 Apr.

  PMID: 29339393 DERIVED

MeSH Terms

Conditions

Urinary Tract Infections; Pyelonephritis

Interventions

finafloxacin; Sodium Chloride; Ciprofloxacin

Condition Hierarchy (Ancestors)

Infections; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Nephritis, Interstitial; Nephritis; Kidney Diseases; Pyelitis

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Prof. Dr. med. Florian Wagenlehner
• Organization: Universityhospital Gießen and Marburg, Germany

Florian.Wagenlehner@chiru.med.uni-giessen.de

+49-641-98544516

Study Officials

• Florian Wagenlehner, Prof.

  Germany: University Hospital Giessen and Marburg, Department of Urology

  PRINCIPAL INVESTIGATOR

• Michal Nowicki, Prof.

  Poland: Medical University Lodz, Department of Nephrology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2013
• First Posted: August 26, 2013
• Study Start: December 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: October 1, 2015
• Last Updated: June 20, 2017
• Results First Posted: June 20, 2017

Record last verified: 2017-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)