PK/PD and Safety/Tolerability of Two Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adults

The study was designed as a randomized, two-way crossover trial involving up to 24 randomized participants with an anticipated drop-out rate no higher than 25% to give a total of 18 evaluable healthy adult participants. The study was fully explained to each participant, informed consent was obtained, and an IRB-approved informed consent form was signed before any study procedures were initiated. All participants underwent screening assessments within 30 days prior to the initial dosing to determine their eligibility for enrollment into the study. All participants met the inclusion and exclusion criteria and underwent screening procedures that included a complete medical history, physical examination, assessment of clinical laboratory parameters (chemistry and hematology), ECG, and pregnancy test (females of child bearing potential only). Randomization was stratified by gender, using permuted blocks. Within each gender, eligible participants were randomized with equal probability to one of the 2 treatment sequences shown in Table 3. According to the sequence to which the participant was randomized, the participant initially received one of two oral dosage regimens of fosfomycin: 3 g every other day x 3 doses or 3 g once-daily x 7 doses. After completion of the initial dosing regimen each participant was crossed over to receive the other dosing regimen. There was a minimum 5-day, and a recommended maximum 14-day, washout period prior to starting the next dosing regimen. Blood and urine samples were collected throughout the study as well as detailed drug administration and adverse event data for each participant. Fosfomycin tromethamine sachet (Monurol™) was used in this study. Each participant was instructed how to stir and dissolve the single-dose sachet into 3 to 4 ounces of water, and take each dose immediately after dissolving in water. Compliance was assessed by participant interviews (every 2 days) and counting of empty of sachets. Participants reported to the outpatient study center on Day -30 to -1 for study criteria review, clinical assessment, and blood collection for screening laboratory tests prior to fosfomycin administration. Each participant participated in the study up to 120 days (i.e., screening visit; day -1 for clinical assessment and blood collection; days 1-7 for fosfomycin administration and sample collection period; and day 8-10 for follow-up assessment; crossed over to receive the other dosing regimen and schedule of events.