Healthy SubjectsPhase 1PROOFNCT02570074

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

A Phase 1 study testing Fosfomycin in people with Healthy Subjects, run by Vance Fowler, M.D. at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Oral dosage regimens for fosfomycin tromethamine (Monurol™) are not established for the treatment of cUTI. The most common and recommended adult dosage regimen in the literature is a single-dose sachet containing the equivalent of 3 grams of fosfomycin administered every other day (QOD) for a total of three doses. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Healthy Subjects
What is being tested?: Fosfomycin
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 19 participants
Where: 1 siteUnited States
Study dates: Jan 2016to Nov 2016
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

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

Show all 11Show fewer

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

Who cannot join

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) <60 ml/minute as determined by Cockcroft-Gault equation
Positive serum pregnancy test.
Currently breast feeding.

Show all 12Show fewer

History of alcohol or substance abuse or dependence within 6 months of the screening: History of regular alcohol consumption averaging >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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Illinois at Chicago
Chicago, Illinois, 60612

Other trials in United States

About this study

Official title: Phase I Study to Evaluate Pharmacokinetics, Pharmacodynamics and Safety/Tolerability of Two Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Participants

There are a myriad of different oral fosfomycin dosing regimens currently being used in clinical practice, including up to 3 grams orally twice daily for 7-21 days, but these regimens are not based on solid pharmacokinetic, pharmacodynamic or safety rationale. Initial pharmacokinetic studies performed with oral fosfomycin tromethamine primarily examined single dose regimens and did not use modern day bioanalytical or pharmacokinetic techniques. As the use of fosfomycin becomes more pervasive in concordance with the increase in multidrug resistant pathogens, further pharmacokinetic and safety data are needed for more intensive dosing regimens to support its continued use.

The rationale of this study is that oral fosfomycin tromethamine requires a modern pharmacokinetic-pharmacodynamic study to identify alternative oral dosage regimens that are appropriate and safe. This study provided safety/tolerability and clinical pharmacology information regarding two oral dosing regimens that may have application to treat various types of infections involving resistant pathogens or when other oral antibacterial options are not available.

Read the detailed description

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.

Conditions: Healthy Subjects
Being tested: Fosfomycin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FosfomycinDrug
Broad spectrum antibiotic

Study groups in NCT02570074
Study group	Role	What they receive
Fosfomycin - 3 doses QoD/7 doses QD	Experimental	Fosfomycin given as a 3 gm dose, every other day for 3 doses, followed by 3 gm dose, once a day for 7 doses. Receives: Drug: Fosfomycin
Fosfomycin - 7 doses QD/3 doses QoD	Experimental	Fosfomycin given as a 3 gm dose, once a day for 7 doses, followed by 3 gm dose, every other day for 3 doses. Receives: Drug: Fosfomycin

What is being measured

The primary outcome is the main question the study is designed to answer.

Number (%) of Grade 2 or Higher AEs Regardless of Relationship to Study Drug
Measured: 3 months
Day 1: Plasma PK Concentrations [mg/L]
Day 1 mean and standard deviation plasma concentrations [mg/L] at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours from dose
Measured: Day 1: 0, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours from dose
Day 5: Plasma PK Concentrations [mg/L]
Day 5 mean and standard deviation plasma concentrations [mg/L] at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours from dose
Measured: Day 5: 0, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours from dose
Maximum Plasma Concentration (Cmax)
To estimate the fosfomycin pharmacokinetic parameter maximum plasma concentration (Cmax) at steady-state for orally-dosed fosfomycin tromethamine in healthy adult participants
Measured: 24 hours
Day 1: Area Under the Concentration Time Curve (AUC 0-infinity)
To estimate the fosfomycin pharmacokinetic parameter area-under-the-plasma concentration-time curve (AUC 0-infinity) at steady-state for orally-dosed fosfomycin tromethamine in healthy adult participants
Measured: 24 hours
Day 5: Area Under the Concentration Time Curve (AUC Tau-infinity)
To estimate the fosfomycin pharmacokinetic parameter area-under-the-plasma concentration-time curve (AUC 0-tau) at steady-state for orally-dosed fosfomycin tromethamine in healthy adult participants
Measured: 24 hours
Number of Subjects Who Prematurely Discontinue Study Drug
Measured: Dosing period: 7 days

Secondary outcomes (20)

Total Body Clearance (CL)
Measured: Pooled over 24 hours: Day 1
Apparent Volume of Distribution (Vss)
Measured: Pooled over 24 hours at Day 1 and Day 5
Elimination Rate Constant (z)
Measured: Pooled over 24 hours at Day 1 and Day 5
Elimination Half-life (t½)
Measured: Pooled over 24 hours at Day 1 and Day 5
Renal Clearance (CLR)
Measured: Pooled over 24 hours at Day 1 and Day 5
Amount Excreted in the Urine (Ae)
Measured: Pooled over 24 hours at Day 1 and Day 5
Urinary Bactericidal (UBT) Titers for E. Coli ATCC 25922
UBT for E.coli ATCC 25922
Measured: 3 months
Urinary Bactericidal Kinetics (UBK)
Measured: 3 months
Urine Fosfomycin Concentrations [mg/L]
Urine Fosfomycin concentrations [mg/L]
Measured: Day 1: 24 hours
UBT-time Curve (AUBT24)
For pathogens E. coli ATCC 25922, E. coli ATCC BAA-2323, K. pneumoniae ATCC 33495, K. pneumoniae ATCC 700603 and P. mirabilis ATCC 35659
Measured: 24 hours at Day 1 and Day 5
Urine Fosfomycin Concentrations [mg/L]
Urine Fosfomycin concentrations [mg/L]
Measured: Day 5: 24 hours
Urinary Bactericidal (UBT) Titers for E. Coli ATCC BAA-2323
UBT for E. Coli ATCC BAA-2323
Measured: 24 hours on Day 1 and Day 5
Urinary Bactericidal (UBT) Titers for K. Pneumoniae ATCC 33495
UBT for E.coli K. Pneumoniae ATCC 33495
Measured: 24 hours on Day 1 and Day 5
Urinary Bactericidal (UBT) Titers for K. Pneumoniae ATCC 700603
UBT for K. Pneumoniae ATCC 700603
Measured: 24 hours on Day 1 and Day 5
Urinary Bactericidal (UBT) Titers for P. Mirabilis ATCC 35659
UBT for P. Mirabilis ATCC 35659
Measured: 24 hours on Day 1 and Day 5
Urinary Inhibitory (UIT) Titers for E. Coli ATCC 25922
UIT for E.coli ATCC 25922
Measured: 24 hours on Day 1 and Day 5
Urinary Inhibitory (UIT) Titers for E. Coli ATCC BAA-2323
UIT for E. Coli ATCC BAA-2323
Measured: 24 hours on Day 1 and Day 5
Urinary Inhibitory (UIT) Titers for K. Pneumoniae ATCC 33495
UIT for E.coli K. Pneumoniae ATCC 33495
Measured: 24 hours on Day 1 and Day 5
Urinary Inhibitory (UIT) Titers for K. Pneumoniae ATCC 700603
UIT for K. Pneumoniae ATCC 700603
Measured: 24 hours on Day 1 and Day 5
Urinary Inhibitory (UIT) Titers for P. Mirabilis ATCC 35659
UIT for P. Mirabilis ATCC 35659
Measured: 24 hours on Day 1 and Day 5

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2016Nov 2016

First posted7 Oct 2015 (estimated)
Study startJan 2016
Primary completionSep 2016
Study completionNov 2016

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Healthy SubjectsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02570074
Sponsor's protocol ID: Pro00066102
Other IDs: 1UM1AI104681-01
Acronym: PROOF
Status last verified: Jul 2019
First submitted: 6 Oct 2015
Last updated: 30 Jul 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Wenzler E, Meyer KM, Bleasdale SC, Sikka M, Mendes RE, Bunnell KL, Finnemeyer M, Rosenkranz SL, Danziger LH, Rodvold KA. Ex Vivo Urinary Bactericidal Activity and Urinary Pharmacodynamics of Fosfomycin after Two Repeated Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Subjects. Antimicrob Agents Chemother. 2020 Jan 27;64(2):e02102-19. doi: 10.1128/AAC.02102-19. Print 2020 Jan 27.
PubMed 31767717
Wenzler E, Bleasdale SC, Sikka M, Bunnell KL, Finnemeyer M, Rosenkranz SL, Danziger LH, Rodvold KA; Antibacterial Resistance Leadership Group. Phase I Study To Evaluate the Pharmacokinetics, Safety, and Tolerability of Two Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Participants. Antimicrob Agents Chemother. 2018 Jul 27;62(8):e00464-18. doi: 10.1128/AAC.00464-18. Print 2018 Aug.
PubMed 29891606

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 30 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Study to Evaluate Pharmacokinetics, Pharmacodynamics and Safety/Tolerability of Two Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Participants
ClinicalTrials.gov ID: NCT02570074
Acronym / sponsor ID: PROOF / Pro00066102
Conditions: Healthy Subjects
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 19 participants (actual)
Lead sponsor: Vance Fowler, M.D.University, hospital or other
Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
Study start: Jan 2016 (actual)
Primary completion: Sep 2016 (actual)
Study completion: Nov 2016 (actual)
First posted: 7 Oct 2015 (estimated)
Results: Posted 30 Jul 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Fosfomycin - 3 doses QoD/7 doses QD	Experimental	Drug: FosfomycinFosfomycin given as a 3 gm dose, every other day for 3 doses, followed by 3 gm dose, once a day for 7 doses.
Fosfomycin - 7 doses QD/3 doses QoD	Experimental	Drug: FosfomycinFosfomycin given as a 3 gm dose, once a day for 7 doses, followed by 3 gm dose, every other day for 3 doses.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (11 listed)

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:
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).

Key exclusion criteria (12 listed)

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) <60 ml/minute as determined by Cockcroft-Gault equation
Positive serum pregnancy test.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FosfomycinBroad spectrum antibiotic	Drug	Fosfomycin - 3 doses QoD/7 doses QD, Fosfomycin - 7 doses QD/3 doses QoD

Primary outcome

Number (%) of Grade 2 or Higher AEs Regardless of Relationship to Study Drug
Time frame: 3 months
Day 1: Plasma PK Concentrations [mg/L]
Time frame: Day 1: 0, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours from dose
Day 1 mean and standard deviation plasma concentrations [mg/L] at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours from dose
Day 5: Plasma PK Concentrations [mg/L]
Time frame: Day 5: 0, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours from dose
Day 5 mean and standard deviation plasma concentrations [mg/L] at 0, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours from dose
Maximum Plasma Concentration (Cmax)
Time frame: 24 hours
To estimate the fosfomycin pharmacokinetic parameter maximum plasma concentration (Cmax) at steady-state for orally-dosed fosfomycin tromethamine in healthy adult participants
Day 1: Area Under the Concentration Time Curve (AUC 0-infinity)
Time frame: 24 hours
To estimate the fosfomycin pharmacokinetic parameter area-under-the-plasma concentration-time curve (AUC 0-infinity) at steady-state for orally-dosed fosfomycin tromethamine in healthy adult participants
Day 5: Area Under the Concentration Time Curve (AUC Tau-infinity)
Time frame: 24 hours
To estimate the fosfomycin pharmacokinetic parameter area-under-the-plasma concentration-time curve (AUC 0-tau) at steady-state for orally-dosed fosfomycin tromethamine in healthy adult participants
Number of Subjects Who Prematurely Discontinue Study Drug
Time frame: Dosing period: 7 days

20 secondary outcomes

Total Body Clearance (CL)
Time frame: Pooled over 24 hours: Day 1
Apparent Volume of Distribution (Vss)
Time frame: Pooled over 24 hours at Day 1 and Day 5
Elimination Rate Constant (z)
Time frame: Pooled over 24 hours at Day 1 and Day 5
Elimination Half-life (t½)
Time frame: Pooled over 24 hours at Day 1 and Day 5
Renal Clearance (CLR)
Time frame: Pooled over 24 hours at Day 1 and Day 5
Amount Excreted in the Urine (Ae)
Time frame: Pooled over 24 hours at Day 1 and Day 5
Urinary Bactericidal (UBT) Titers for E. Coli ATCC 25922
Time frame: 3 months
Urinary Bactericidal Kinetics (UBK)
Time frame: 3 months
Urine Fosfomycin Concentrations [mg/L]
Time frame: Day 1: 24 hours
UBT-time Curve (AUBT24)
Time frame: 24 hours at Day 1 and Day 5
Urine Fosfomycin Concentrations [mg/L]
Time frame: Day 5: 24 hours
Urinary Bactericidal (UBT) Titers for E. Coli ATCC BAA-2323
Time frame: 24 hours on Day 1 and Day 5
Urinary Bactericidal (UBT) Titers for K. Pneumoniae ATCC 33495
Time frame: 24 hours on Day 1 and Day 5
Urinary Bactericidal (UBT) Titers for K. Pneumoniae ATCC 700603
Time frame: 24 hours on Day 1 and Day 5
Urinary Bactericidal (UBT) Titers for P. Mirabilis ATCC 35659
Time frame: 24 hours on Day 1 and Day 5
Urinary Inhibitory (UIT) Titers for E. Coli ATCC 25922
Time frame: 24 hours on Day 1 and Day 5
Urinary Inhibitory (UIT) Titers for E. Coli ATCC BAA-2323
Time frame: 24 hours on Day 1 and Day 5
Urinary Inhibitory (UIT) Titers for K. Pneumoniae ATCC 33495
Time frame: 24 hours on Day 1 and Day 5
Urinary Inhibitory (UIT) Titers for K. Pneumoniae ATCC 700603
Time frame: 24 hours on Day 1 and Day 5
Urinary Inhibitory (UIT) Titers for P. Mirabilis ATCC 35659
Time frame: 24 hours on Day 1 and Day 5

Results and safety

Results posted to the registry on 30 Jul 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Fosfomycin - 3 Doses QoD/7 Doses QD	9	9
Fosfomycin - 7 Doses QD/3 Doses QoD	10	10

Primary outcome: Number (%) of Grade 2 or Higher AEs Regardless of Relationship to Study Drug

Time frame: 3 months. Count of participants. Unit: Participants

Measure	Fosfomycin - 3 Doses QoD Regimen n = 19	Fosfomycin - 7 Doses QD Regimen n = 18
Value	1	3

Primary outcome: Day 1: Plasma PK Concentrations [mg/L]

Time frame: Day 1: 0, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours from dose. Mean (Standard Deviation). Unit: mg/L

Measure	Fosfomycin - 3 Doses QoD n = 18	Fosfomycin - 7 Doses QD n = 18
0 hours	0.08 (0.36)	0 (0)
1 hour	16.61 (5.44)	15.90 (6.70)
1.5 hours	22.20 (7.98)	21.35 (7.17)
2 hours	23.36 (7.04)	22.12 (6.34)
3 hours	18.72 (5.13)	17.86 (4.67)
4 hours	14.08 (4.00)	13.53 (3.87)
6 hours	9.11 (2.38)	8.43 (2.38)
8 hours	6.08 (1.48)	5.69 (1.57)

Population analysed: Please note that one person did not complete the Fosfomycin 3 doses QoD regimen.

Primary outcome: Day 5: Plasma PK Concentrations [mg/L]

Time frame: Day 5: 0, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours from dose. Mean (Standard Deviation). Unit: mg/L

Measure	Fosfomycin - 3 Doses QoD n = 18	Fosfomycin - 7 Doses QD n = 18
0 hours	0.23 (0.37)	1.33 (1.12)
1 hour	16.29 (6.23)	16.81 (4.27)
1.5 hours	21.21 (6.91)	22.07 (5.02)
2 hours	22.48 (6.44)	23.37 (5.71)
3 hours	19.38 (5.34)	19.45 (5.10)
4 hours	14.98 (4.82)	15.12 (4.27)
6 hours	9.78 (3.08)	9.91 (2.74)
8 hours	6.47 (1.95)	6.93 (1.96)

Population analysed: Please note that one person did not complete the Fosfomycin 3 doses QoD regimen.

Primary outcome: Maximum Plasma Concentration (Cmax)

Time frame: 24 hours. Mean (Standard Deviation). Unit: mg/L

Measure	Fosfomycin - 3 Doses QoD Regimen n = 18	Fosfomycin - 7 Doses QD Regimen n = 18
Day 1	23.79 (7.48)	23.47 (6.62)
Day 5	24.41 (6.23)	23.75 (5.61)

Population analysed: Please note that one person did not complete the Fosfomycin 3 doses QoD regimen.

20 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data were collected though 60 days following the final study visit. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Fosfomycin - 3 Doses QoD	1 of 19 (5.3%)	16 of 19 (84.2%)	0 of 19
Fosfomycin - 7 Doses QD	1 of 18 (5.6%)	16 of 18 (88.9%)	0 of 18

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31767717Wenzler E, Meyer KM, Bleasdale SC, Sikka M, Mendes RE, Bunnell KL, Finnemeyer M, Rosenkranz SL, Danziger LH, Rodvold KA. Ex Vivo Urinary Bactericidal Activity and Urinary Pharmacodynamics of Fosfomycin after Two Repeated Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Subjects. Antimicrob Agents Chemother. 2020 Jan 27;64(2):e02102-19. doi: 10.1128/AAC.02102-19. Print 2020 Jan 27.
Derived from this study: PubMed 29891606Wenzler E, Bleasdale SC, Sikka M, Bunnell KL, Finnemeyer M, Rosenkranz SL, Danziger LH, Rodvold KA; Antibacterial Resistance Leadership Group. Phase I Study To Evaluate the Pharmacokinetics, Safety, and Tolerability of Two Dosing Regimens of Oral Fosfomycin Tromethamine in Healthy Adult Participants. Antimicrob Agents Chemother. 2018 Jul 27;62(8):e00464-18. doi: 10.1128/AAC.00464-18. Print 2018 Aug.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Vance Fowler, MD principal investigator

Duke University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Fosfomycin in people with Healthy Subjects, run by Vance Fowler, M.D. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number (%) of Grade 2 or Higher AEs Regardless of Relationship to Study Drug (time frame: 3 months). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02570074, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2019.