uncomplicated lower urinary tract infections (acute or recurrent) MedDRA version: 20.0 Level: HLT Classification code 10046577 Term: Urinary tract infections System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.0 Level: PT Classification code 10046571 Term: Urinary tract infection System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.0 Level: LLT Classification code 10024981 Term: Lower urinary tract infection System Organ Class: 10021881 - Inf
Conditions
Sponsors
ADAMED Pharma S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria The patients meeting the below mentioned criteria will be included into the study: 1. Informed Consent: Willingness to comply with all the study activities and procedures and provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses. For pediatric population, parents’ or legal guardian’s informed consent will be required. 2. Age: Subject must be = 12 years of age at the time of signing the informed consent form.Germany only: Subject must be = 18 years of age at the time of signing the informed consent form. 3. Sex: female. 4. Patients with diagnosis of the acute or recurrent uncomplicated lower urinary tract infection (cystitis). For the purposes of this study, urinary tract infection (cystitis) is defined by: a) presence of at least two of the following clinical symptoms: dysuria, urinary frequency, urinary urgency, suprapubic pain, and b) at least a score of 6 of typical symptoms obtained by the Acute Cystitis Symptom Score (ACSS) questionnaire applied as additional tool for the clinical inclusion criteria defined by the draft guideline on the evaluation of medicinal products indicated for treatment of bacterial infections (EMA/844951/2018 Rev. 3) and c) presence of pyuria, as determined by a dipstick test positive for leukocyte esterase or at least 10 leukocytes per cubic millimeter [1 µl] (WBC = 10/mm3) as required by the draft EMA Guideline (EMA/844951/2018 Rev. 3). 5. Onset of symptoms of urinary tract infection at least 12 hours but not more than 72h prior to Visit 1 (Screening). 6. No prior treatment with systemic antibiotics and/or chemotherapeutic agents for any reason within 7 days prior to Visit 1. 7. Negative urine pregnancy test for female subjects of childbearing potential. 8. Female patients must be post-menopausal (i.e.: no menstrual bleeding for at least 12 consecutive months), surgically sterile (i.e. after surgery as bilateral tubal ligation, bilateral ovarectomy or hysterectomy), or using an highly-effective method of contraception (defined as: combined oral, transdermal or intravaginal (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner, sexual abstinence). Additional barrier methods in conjunction with spermicide are recommended to be used. Are the trial subjects under 18? yes Number of subjects for this age range: 12 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 612 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 12
Exclusion criteria
Exclusion criteria: Patients must not meet any of the following exclusion criteria: 1. Symptoms suggesting probability of SARS-CoV-2 infection or known positive COVID-19 rapid antigen test within last 7 days. 2. Direct contact with a person suffering from COVID-19 within 14 days before Visit 1. 3. Traveled and stayed more than 48 hours in the country affected with SARS-CoV-2 transmition within 14 days before Visit 1, with an exemption of fully anti-COVID-19 vaccinated patients. 4. Any symptoms of complicated urinary tract infections (cUTI), pyelonephritis (i.e., fever T = 38.0°C, flank pain (costovertebral angle pain), chills and/or inflammation of the vulva and vagina and/or abnormal discharge from the vagina or urethra) at Visit 1. 5. Known clinically significant anatomic and functional disorders of the urinary tracts (including, but not limited to congenital malformations, conditions after surgery within the urogenital tracts during the last 30 days, clinically significant residual urine (more than 100 ml of urine being retained in urinary bladder based on PVR USG examination*), neurogenic bladder, urolithiasis, urogenital system malignancies) allowing to recognize complicated urinary tract infection. 6. Previous UTI episode treated (resolved or unresolved) within 4 weeks before Visit 1. 7. As judged by the investigator, any evidence of disease/condition which in the investigator’s opinion makes it undesirable for the subject to participate in the trial. 8. Any intake of systemic bacteriostatic agents and/or antibiotics within 7 days prior to Visit 1 and OTC drugs, including ibuprofen and other NSAIDs, and/or dietary supplements, food preparations used in the urinary tract infections, within 7 days prior to Visit 1, with an exemption for acetylosalicylic acid at a stable dose of 75 mg or 150 mg per day, taken over 30 days before Visit 1 to reduce blood clotting. 9. Hypersensitivity to furazidin, nitrofurantoin, nitrofuran derivatives or other drug components. 10. Other acute infections (except for acute UTI) requiring antibiotic treatment at Visit 1. 11. Catheter in the bladder or any other foreign body in the urinary tracts. 12. Overactive bladder. 13. Menstrual bleeding at the day of visit. 14. Immunomodulatory prophylaxis due to urinary tract infection within 6 months prior to Visit 1. 15. Treatment with vitamin K antagonists (Warfarin, Acenocumarol) as long the INR test is out of the normal values resulting in significant haematuria (decision about randomization to be made based on the last INR result), probenecid, sulfinpirazon, alkalising drugs containing magnesium trisilicate, ristomycin, metoclopramide, nalidixic acid, atropine, levomicetin, sulphanilamide within 7 days before Visit 1. 16. The presence of known severe renal impairment. 17. The known presence of: a. severe abdominal pain with special attention to pancreatitis (strong abdominal pain in the area of epi- or mesogastrium, girdle or radiating to back area, nausea and vomiting, diarrhorea) b. electrolytes disturbancies (based on symptoms assessment: irregular heartbeat, tachycardia, fatigue, lethargy, convulsions or seizures, nausea, vomiting, diarrhea or constipation, abdominal cramping, muscle cramping, muscle weakness, irritability, confusion, headaches, numbness and tingling) c. polycystic kidney disease, severe pulmonary disease, diagnosed polyneuropathy, e.g. diabetic polyneuropathy, known glucose-6-phosphate dehydrogenase deficiency, anemia, known deficiency of vitamins B an
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to demonstrate at least the same efficacy (a non-inferiority design) of Furazidin PR versus Nitrofurantoin PR in the treatment of the uncomplicated lower urinary tract infections (cystitis) in women (acute or recurrent).;Secondary Objective: The secondary objectives of the study are: • assessment of microbial response; • assessment of clinical response; • patient assessment of efficacy and quality of life; • evaluation of patient compliance with dosing regimen; • evaluation of safety profile; • observation of the treatment efficacy during Visit 2 at Day 5 (First Resolution) to find out whether the study results will be supportive enough to make the treatment posology shorter); • evaluation of patient compliance with dosing recommendation in respect to the meals.;Primary end point(s): The primary efficacy criteria is defined as a composite endpoint consisting of the resolution or improvement of all clinical symptoms of urinary tract infection without need of additional antibacterial therapy and the efficacy measure according to the ACSS self-assessment scale (a score of typical symptoms of the ACSS = 5 but no item > 1 (mild) and no visible blood in urine) and the demonstration that the bacterial pathogen found at trial entry in CFU > 10^5 / mL is reduced to fewer than 103 CFU/mL on urine culture during Visit 4 (Test of Cure Visit, Day 14 (+/- 2)).;Timepoint(s) of evaluation of this end point: 14 days (+/- 2 days) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy parameters include the following: • Number of patients that achieved resolution or improvement of all clinical symptoms of UTI according to the ACSS self-assessment scale (a score of typical symptoms of ACSS = 5 but no item > 1 (mild)) and no visible blood in urine at Visit 2 (First Resolution), Visit 3 (End of Treatment), Visit (Test of Cure), and Visit 5 (Follow up) in Furazidin PR arm in relation to Nitrofurantoin PR arm; [Time Frame: Day 5, Day 7, Day 14, Day 28]; • Number of patients that achieved reduction of pathogens count, present at the study entry (at Visit 1), to a level 10^3/ ml), regardless the baseline bacteriuria CFU > or = 10^5/ml and nitrofurantoine susceptibility will be assessed for microbiological secondary endpoint. • Number of patients with new infections at Visit 4 [Time Frame: Day 14]. • Number of patients with a need of any other antimicrobial medication intake for UTI between Visit 1 and Visit 4 and between Visit 1 and Visit 5 in Furazidin PR arm in relation to Nitrofurantoin PR arm; [Time Frame: Day 5, Day 7, Day 14, Day 28]; • Maintenance of clinical response until Day 28 (Visit 5 - Follow up) in Furazidin PR arm in relation to Nitrofurantoin PR arm, based on the ACSS self-assessment scale (a score of typical symptoms of ACSS = 5 but no item > 1 (mild)) and no visible blood in urine); [Time Frame: Day 28]; • Change in the patient self-reporting quality of life using the ACSS questionnaire at Visit 1, Visit 2 (First Resolution), Visit 3 (End of treatment), Visit 4 (Test of Cure), Visit 5 ( Follow-up); in Furazidin PR arm in relation to Nitrofurantoin PR arm; [Time Frame: Day 1, Day 5, Day 7, Day 14, Day 28]; • Number of Treatment-Emergent AEs/ SAEs collected during the course of the study since Visit 1 until Visit 5 in Furazidin PR arm in relation to Nitrofurantoin PR; [Time Frame: Day 1 to Day 28]; • The susceptibility of infecting strains to Furazidin PR and Nitrofurantoin PR; [Time Frame: Day | — |
Countries
Germany, Hungary, Poland, Russian Federation
Contacts
Public ContactPiotr Witkowski
ADAMED Pharma S.A.
Outcome results
None listed