E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
acute uncomplicated lower urinary tract infections |
|
E.1.1.1 | Medical condition in easily understood language |
acute uncomplicated lower urinary tract infections |
|
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 | 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 |
|
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 current European Association of Urology guidelines on urological infections (EAU Guidelines 2020) recommend oral antibiotics (e.g. fosfomycin trometamol, pivmecillinam, nitrofurantoin) as first-line treatment for acute lower urinary tract infection (UTI, also called cystitis) in women. This randomised controlled clinical trial aims to investigate D-mannose (Femannose® N) as stand-alone therapy for acute uncomplicated UTI to point out possible strategies for the avoidance of so far common antibiotic use. |
|
E.2.2 | Secondary objectives of the trial |
Objectives: - To gain further information on clinical effectiveness and safety / tolerability of 5 days oral treatment with D-mannose in comparison to a single oral dose of fosfomycin with regard to clinical cure of acute uncomplicated cystitis in women - To compare the bacteriologic response to oral treatment with D-mannose and fosfomycin for acute uncomplicated cystitis - To assess the safety and tolerability of oral treatment with D-mannose and fosfomycin for acute uncomplicated cystitis
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Female outpatients aged 18 to 70 years 2.Clinical signs and symptoms of an acute uncomplicated cystitis (e.g. dysuria, pollakisuria, and / or urgency to urinate) starting not earlier than 72 hours prior to trial enrolment at Visit 1 3.Signed informed consent and data protection form 4.ACSS-“Typical” domain score is ≥6 at Visit 1 5.Urine dipstick test (midstream sample) is positive for leukocytes at Visit 1
|
|
E.4 | Principal exclusion criteria |
1.Males 2.Pregnant or lactating females or females of childbearing potential who are not using an effective method of contraception 3.Females with episodes of acute cystitis within 4 weeks before enrolment (Visit 1) or females with ≥3 episodes of acute cystitis within 6 months before enrolment 4.Anamnestic proof of presence of any predisposing factors or any conditions that may promote or lead to (complicated) urinary tract infections (i.e., anamnestic proof of renal insufficiency, renal calculi, polycystic kidneys, urinary tract abnormalities or past urinary surgery, urine catheterisation, spinal cord injury, etc.) 5.Anamnestic proof of renal impairment (creatinine clearance <30 mL / min) 6.Anamnestic proof of diabetes mellitus (Type I and II) 7.Any signs of pyelonephritis (i.e., fever ≥38.0°C tympanic, flank and / or back pain, chills or shivers) 8.Vulvovaginitis with abnormal vaginal and / or with urethral discharge (without urination) at Visit 1 9.Known or suspected hypersensitivity to one or more of the ingredients of the test product (Femannose® N) and / or comparator (Fosfomycin HEXAL®) and / or any placebo used 10.Systemic or local (i.e. vaginal) treatment with antibiotics within 7 days prior to Visit 1 11.Treatment with analgesics (e.g. nonsteroidal anti-inflammatory drugs, NSAIDs) within 6 hours prior to Visit 1 12.Parallel participation in another clinical study or trial, participation in a clinical study or trial within the previous 4 weeks prior to Visit 1, or previous participation in this clinical trial 13.Known to be or suspected of being unable to comply with the trial protocol (e.g. no permanent address, history of or (and) known drug abuse, known to be non-compliant or presenting an unstable psychiatric history) 14.Legal incapacity and / or other circumstances which makes the subject unable to understand the nature, scope and possible impact of the investigation 15.Custody by juridical or official order 16.Evidence of an uncooperative attitude (non-compliance) 17.Difficulties in understanding the language in which the informed consent and data protection declaration is given 18.Investigational site staff, staff of the sponsor or involved clinical research organisation (CRO), the investigator him- / herself or close relatives
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Definitions: - CLINICAL CURE is defined as ACSS-“Typical” domain score ≤4 (sum of the 6 scores within the domain) whereby items 1-5 must be scored “1” (mild) or “0” (not present), and item 6 must be scored “0” (absence of haematuria, i.e. no visible blood in urine). - A positive urine culture is defined as either ≥10^3 CFU/mL of culture (with a maximum of 2 species) of uropathogens, or a positive mixed urine culture ≥10^3 CFU/mL as defined by the MIQ 02/2020 guidance. - A negative urine culture is defined as <10^3 CFU/mL or a log reduction of at least 1 (≥ 90%) of the same species as compared to Visit 1. Efficacy endpoints 1: Percentage of subjects with CLINICAL CURE separately on Day 8 or Visit 3 and on both time points 2: Time to first day of CLINICAL CURE within the first 8 days of the active phase of the trial 3: Percentage of subjects with a negative urine culture at Visit 2 4: Percentage of subjects with CLINICAL CURE and a negative urine culture at Visit 2 5: Percentage of subjects with CLINICAL CURE and ACSS-“QoL” domain score ≤3 but no “QoL” domain item >1 on Day 8 6: Percentage of subjects with recurrence of UTI established by ACSS-“Typical” domain score ≥6 during the follow-up phase 7: Percentage of subjects with antibiotic therapy for acute UTI in the acute phase (Visit 1 – Visit 2, in addition to the trial treatment), in the follow-up phase (Visit 2 – Visit 3: recurrence by antibiotic therapy), and in both trial phases (Visit 1 – Visit 3) 8: Time to recurrence of UTI as determined by the first date of the ACSS-“Typical” domain score ≥6 during the follow-up phase 9: Time to recurrence of UTI as determined by the first date of antibiotic use for acute UTI during the follow-up phase 10: Change in ACSS-“Typical” domain score on Day 8 compared to Visit 1 11: Change in ACSS-“QoL” domain score on Day 4 and Day 8 each compared to Visit 1 12: Change in the total score calculated as the sum of the two domain scores ACSS-“Typical” and ACSS-“QoL” on Day 8 compared to Visit 1 13: Change in time course of the ACSS-“Dynamic” domain score from Day 1 to Day 8 14: Investigator’s and subject’s global judgement on efficacy at Visit 2 and Visit 3 Safety endpoints (SEP) 1: Adverse events (type, frequency, severity, seriousness, causal relationship to IMD / IMP) 2: Change in vital signs at Visit 2 and Visit 3 each compared to Visit 1 3: Investigator’s and subject’s global judgement on tolerability at Visit 2 and Visit 3 4: Percentage of subjects with co-medication at Visit 2 and Visit 3 each compared to Visit 1
|
|
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 | No |
E.6.7 | Pharmacodynamic | No |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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) | Yes |
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 | 30 |
E.8.5 | The trial involves multiple Member States | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |