Evaluation of the Safety and Efficacy of Oral Fosfomycin Calcium Versus Fosfomycin Trometamol in Adult Women with Uncomplicated Urinary Tract Infection

The primary objective of this clinical trial is to assess the **efficacy** of oral fosfomycin calcium in achieving clinical and microbiological resolution of uncomplicated urinary tract infection (**uUTI**) in adult women, comparing its non-inferiority to fosfomycin trometamol. This evaluation is clinically relevant as it aims to establish an alternative treatment option for uUTI, potentially offering similar therapeutic outcomes with a different formulation.

Secondary objectives include monitoring the **safety** and **tolerability** of the dose regimen of oral fosfomycin calcium capsules when administered to adult women with uUTI. This is crucial for ensuring that the treatment is not only effective but also safe for patient use, minimizing adverse effects and improving patient compliance.

The clinical trial focuses on evaluating the efficacy of **fosfomycin calcium** in the treatment of **uncomplicated urinary tract infection (uUTI)** in women. The study population comprises adult women aged 18 years and older, specifically targeting those who present with initial uUTI symptoms. Participants must exhibit at least two of the following signs: urinary frequency, urinary urgency, dysuria, or suprapubic pain. Additionally, a mid-stream urine specimen must test positive for leukocyte esterase, indicating pyuria. The trial exclusively includes female subjects, with no male participants involved, and does not target any vulnerable populations. Participants are required to use effective birth control methods if they are of childbearing potential. The sponsor has not provided information regarding the total number of participants in the study. The selection criteria ensure that participants are able to communicate effectively and provide written informed consent, ensuring a clear understanding of the trial requirements and procedures.

The clinical trial is designed as a **randomized**, double-blind, double-dummy, parallel-group, multicenter study to evaluate the safety and clinical and microbiologic efficacy of oral **fosfomycin calcium** in adult women with uncomplicated urinary tract infection (**uUTI**). The primary objective is to assess the non-inferiority of fosfomycin calcium compared to fosfomycin trometamol in achieving clinical and microbiological resolution of uUTI. The trial is expected to commence recruitment on May 2, 2023, and conclude by December 30, 2025, with an estimated duration of participant involvement of up to three days, corresponding to the maximum treatment period.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, symptoms, and urine analysis. Eligible participants are adult women aged 18 years or older, presenting with at least two signs of uUTI, and a positive dipstick analysis for leukocyte esterase. Women of childbearing potential must adhere to effective birth control methods. Following the screening, participants will be randomized to receive either fosfomycin calcium or a comparator, with the treatment administered orally. The primary endpoint will be evaluated at the Test of Cure (TOC) visit, where clinical resolution of symptoms and microbiological response, defined as a reduction of bacterial pathogens to less than 1000 CFU/mL in urine culture, will be assessed. Secondary endpoints include the proportion of subjects with continued clinical and microbiologic success at the TOC visit.

The trial will include follow-up visits to monitor safety and efficacy outcomes, with the end-of-study visit marking the conclusion of participant involvement. Conditions that may lead to early termination from the study include adverse events, withdrawal of consent, or non-compliance with study procedures. The trial is categorized as a phase 4 study, indicating its focus on post-marketing surveillance to further evaluate the therapeutic efficacy and safety of the investigational product.

The clinical trial involves the administration of **fosfomycin calcium**, an experimental medication, to evaluate its safety and efficacy in the treatment of uncomplicated urinary tract infections (uUTI) in adult women. **Fosfomycin calcium** is a chemical substance classified under the ATC code J01XX01, indicating its use as an antibiotic. The pharmaceutical form of the medication is denoted by the code PHF00170MIG, and it is administered orally. The maximum daily dose of **fosfomycin calcium** is 1500 mg, with a total maximum dose of 500 mg per administration. The treatment period is limited to a maximum of 3 days. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed regimen.

In addition to the experimental treatment, the study employs a double-blind, double-dummy design, which may involve the use of a placebo or comparator treatment, such as **fosfomycin trometamol**, to assess the non-inferiority of **fosfomycin calcium**. The trial aims to determine the clinical and microbiological resolution of uUTI, comparing the efficacy of the experimental medication against the standard treatment. The study protocol ensures that all participants receive either the experimental medication or the comparator treatment, maintaining the integrity of the trial's blinding process.

The efficacy of **fosfomycin calcium** in the treatment of uncomplicated urinary tract infections (uUTI) in adult women will be assessed through both clinical and microbiological endpoints. The primary endpoint is the resolution of uUTI symptoms and the reduction of bacterial pathogens to less than 1000 CFU/mL in urine culture, evaluated in the microbiological intent-to-treat (ITT) population at the Test of Cure (TOC) visit. Secondary endpoints include the proportion of subjects achieving continued clinical and microbiological success, also assessed at the TOC visit.