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

Inclusion Criteria

• The participant is healthy as judged by the site investigator with no clinically significant abnormality identified on a medical evaluation including history, physical examination, laboratory tests, blood pressure, and heart rate.
• Male and female participants between 18 to 55 years old.
• Female participants of childbearing potential (not surgically sterilized and between menarche and one-year post-menopause) must have a negative pregnancy test at the time of enrollment and must agree to use appropriate contraception for as long as they are taking the study drug and for 1 month afterwards. During the screening visit, participants will be instructed to use a second reliable method of birth control in accordance with the protocol during the study and for one month following. Medically acceptable contraceptives include:
• Surgical sterilization (such as a tubal ligation or hysterectomy)
• Approved hormonal contraceptives (such as birth control pills, patches, implants or injections)
• Barrier methods (such as a condom or diaphragm) used with a spermicide, or
• An intrauterine device (IUD). i. NOTE: Contraceptive measures such as Plan B™, sold for emergency use after unprotected sex, are not acceptable methods for routine use.
• Nonsmokers defined as abstinence from cigarette smoking for the previous 6 months before enrollment into the study.
• Provide a signed and dated written informed consent prior to any study-specific procedures (including screening procedures).
• Body weight ≥50 kg
• Body mass index (BMI) 18.5-29.9 kg/m2

Exclusion Criteria

• History of significant hypersensitivity reaction or intolerance to fosfomycin tromethamine that in the opinion of the site investigator, contraindicates participation in the study. In addition, if heparin is used during pharmacokinetic sampling, participants with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
• History of significant cardiac, neurological, thyroid, muscular, or immune disorder.
• Any laboratory abnormality grade 2 or higher as defined according to the U.S. Department of Health and Human Services common terminology criteria for AEs (CTCAE).26
• Estimated creatinine clearance (CLCR) 7 drinks/week for women or >14 drinks/week for men. 1 drink is equivalent to 12g alcohol = 5 oz (150 mL) of wine or 12 oz (360 mL) of beer or 1.5 oz (45 mL) of 80 proof distilled spirits.
• The use of prescription (except birth control pills or hormone replacement in females) or non-prescription drugs, including herbal and dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of site investigator the medication will not interfere with the study procedures or compromise participant safety.
• The participant has participated in a clinical trial and has received a drug or a new chemical entity within 30 days prior to the first dose of study medication.
• Participants who have donated blood to the extent where participation in the study would result in excess of 500 mL blood donated within a 56 day period.
• Those who, in the opinion of the site investigator, have a risk of non-compliance with study procedures.
• QTc interval with Fredericia correction >450ms or any other clinically relevant ECG abnormalities