E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
uncomplicated lower urinary tract infections (acute or recurrent) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10046577 |
E.1.2 | Term | Urinary tract infections |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10046571 |
E.1.2 | Term | Urinary tract infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024981 |
E.1.2 | Term | Lower urinary tract infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10038140 |
E.1.2 | Term | Recurrent urinary tract infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to assess the effectiveness of Furazidin PR in treatment of uncomplicated UTI (acute or recurrent). |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the study are: • to assess pharmacokinetics and pharmacodynamics (PK/PD) of Furazidin PR in general and special patient populations with uncomplicated UTI (acute or recurrent), • to model PK/PD relationships and assess demographic covariates and/or subpopulations in PK/PD relationships, • to evaluate safety profile of Furazidin PR, • to assess quality of life in UTI patients’ population, • observation of the treatment effectiveness at the Day 5 (First Resolution), • evaluation of patient compliance with dosing recommendation in respect to the meals, • evaluation of patients’ compliance with recommended dose regimens of Furazidin PR. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 patients < 18 years old – parents’ informed consent is required. 2. Age: Subject must be ≥ 12 years of age at the time of signing the informed consent form. 3. Sex: female. 4. Patients with diagnosis of uncomplicated lower urinary tract infection (acute or recurrent). For the purposes of this study, urinary tract infection 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 (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 72 hours 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; NOTE: in case of any antimicrobial therapy administrated > 7 days before Visit 1, each treatment should be evaluated individually by the Investigator to assess the risk of PK or PD carryover from previous antibiotics/ chemotherapeutic agents. 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), or - surgically sterile (i.e. after surgery as bilateral tubal ligation, bilateral ovariectomy or hysterectomy), or - abstain from sexual intercourse, or - using an acceptable and highly-effective method of contraception for the duration of the study and for 1 month after the last dose of Furazidin PR to prevent pregnancy, 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, Additional barrier methods in conjunction with spermicide is recommended. |
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E.4 | Principal exclusion criteria |
1. Positive COVID-19 rapid antigen test on Visit 1. 2. 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. 3. 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. 4. Previous UTI episode treated (resolved or unresolved) within 4 weeks before Visit 1. 5. The known contraindications for furazidin treatment: a. severe abdominal pain with special attention to signs and symptoms of pancreatitis (strong abdominal pain in the area of epi- or mesogastrium, girdle or radiating to back area, nausea and vomiting, diarrhoea) – data obtained on the basis of patient medical interview and physical examination. b. electrolytes disturbances (based on symptoms assessment: irregular heartbeat, tachycardia, fatigue, lethargy, convulsions or seizures, nausea, vomiting, diarrhoea or constipation, abdominal cramping, muscle cramping, muscle weakness, irritability, confusion, headaches, numbness and tingling) – data obtained on the basis of patient medical interview and physical examination. c. polycystic kidney disease, severe pulmonary disease, diagnosed polyneuropathy, e.g. diabetic polyneuropathy, known glucose-6-phosphate dehydrogenase deficiency, anaemia, known deficiency of vitamins B and folic acid, neutropenia, severe thrombocytopenia, liver failure, porphyria, immunosuppressive or immunomodulatory treatment, HIV/AIDS infection, chemotherapy, steroid therapy, fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency – data obtained on the basis of patient medical history. 6. 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; 7. Hypersensitivity to furazidin, nitrofurantoin, nitrofuran derivatives or other drug components. 8. Any intake of systemic antibiotics and/or bacteriostatic agents within 7 days prior to Visit 1. 9. Any intake of systemic OTC drugs, within 7 days prior to Visit 1 including: - ibuprofen and other NSAIDs, and / or - dietary supplements and food preparations used in the urinary tract infections, 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. The known history of cancer disease, that is not cured nor stable within 12 months prior to Visit 1. 14. Active peptic ulcers. 15. Menstrual bleeding at the day of visit. 16. Immunomodulatory prophylaxis due to urinary tract infection within 6 months prior to Visit 1; 17. The presence of known severe renal impairment. 18. Treatment with vitamin K antagonists (Warfarin, Acenocumarol) as long the INR test is out of the normal values resulting in significant haematuria (decision about enrolment 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. 19. Current or previous history of addiction to alcohol and/or drugs. 20. Patients who are expected to have problems with the insertion of intravenous catheters or venipuncture. 21. Investigator’s opinion that the patient should not participate in the study if the subject is unlikely to comply with study procedures, restrictions, and requirements. 22. The legal inability and/or other circumstances that prevent the patient's understanding of the extent and possible influence of the study. 23. Sound suspicion that the patient fails to comply with the study protocol directives. 24. Are currently enrolled in or discontinued within the last 30 days from a clinical trial involving an investigational drug including furazidin, nitrofurantoin, and/ or nitrofuran derivatives, or device or off-label use of a drug or device other than the study drug/device used in this study, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. 25. Are currently pregnant (confirmed with positive urine pregnancy test) or breast-feeding. 26. Are Sponsor’s /CRO’s employees/relatives or investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy criterion 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 at CFU > 10^5/ mL is reduced to fewer than 10^3 CFU/mL on urine culture during Visit 5 (Test of Cure Visit, 9 (+2) days after treatment initiation). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Assessment of population PK parameters of Furazidin PR in uncomplicated UTI (acute or recurrent) patient population such as clearance and volume of distribution including demographic covariate testing and/or subpopulation analysis, • Bacteriological assessment (PD) including pathogen identification and observed changes in bacterial count (CFU/mL) during the 7-day therapy with Furazidin PR; [Time Frame: Day 1, Day 2, Day 5, Day 7, Day 9], • Assessment of population PK/PD relationship and parameters including demographic covariate testing and/or subpopulation analysis, • 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 3 (First Resolution), Visit 4 (End of Treatment), Visit 5 (Test of Cure), and Visit 6 (Follow-up); [Time Frame: Day 5, Day 7, Day 9, Day 28], • Number of patients that achieved reduction of pathogens count, present at the study entry (at Visit 1), to a level <103 CFU/mL in urine culture at Visit 5; [Time Frame: Day 9], • Number of patients with new infections; [Time Frame: Day 9], • Number of patients with a need of any other antimicrobial medication intake for UTI between Visit 1 and Visit 5 and between Visit 1 and Visit 6; [Time Frame: Day 2, Day 5, Day 7, Day 9, Day 28], • Maintenance of clinical response until Day 28 (Visit 6 - Follow up) 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 (Baseline), Visit 2 (PK/PD sampling), Visit 3 (First Resolution), Visit 4 (End of treatment), Visit 5 (Test of Cure), Visit 6 (Follow-up); [Time Frame: Day 1, Day 2, Day 5, Day 7, Day 9, Day 28], • Number of Treatment-Emergent AEs/ SAEs collected during the course of the study since Visit 1 until Visit 6; [Time Frame: Day 1 to Day 28], • The susceptibility of infecting strains to Furazidin PR and other antibiotics used for UTI treatment; [Time Frame: Day 1, Day 9], • Patient compliance with study treatment dosing regimen, defined as the range of 71-129% of total dose of study treatment that should be taken during the course of the study; [Time Frame: Day 9], • Patient compliance of study treatment administration in respect to meals; compliance defined as at least 71% doses administrated as per recommendations; [Time Frame: Day 9], • Clinical response to study treatment in relation to patient compliance with study treatment administration in respect to meals; [Time Frame: Day 9]. NOTE: All patients meeting study entry criteria with positive bacteriuria, CFU > 10^3/mL will be assessed for secondary microbiological endpoints. NOTE: Patients who entered the study and received study medication but failed to fulfill study microbiological inclusion criteria will be evaluated in the same manner as above. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |