Eligibility Details:
Inclusion Criteria:
1. Healthy* men and women aged 18-45 years with no clinically significant findings** at
Screening and Baseline (Day -1 to Day 1)
*Healthy is defined by the absence of any medical condition described in the exclusion
criteria in a subject with a normal physical exam including vital signs. If the
subject has another current, ongoing medical condition, the condition cannot meet any
of the following criteria: 1) first diagnosed within 3 months of enrollment; 2) is
worsening in terms of clinical outcome in the last 6 months; or 3) involves need for
medication.
**Including findings on medical history, physical exam, vital signs, 12-lead
Electrocardiogram (ECG), or clinical laboratory tests.
2. Body Mass Index (BMI) = 18 - 30 kg / m^2, inclusive, and body weight > 50 kg (110
lbs).
3. Females who have been surgically sterilized via bilateral oophorectomy and/or
hysterectomy at least 90 days prior to Screening are considered lacking childbearing
potential and will be eligible*.
*Postmenopausal females are not eligible, as the definition of menopause would require
age > 45, and all subjects in this study are age < / = 45.
4. Females of childbearing potential must have a negative serum pregnancy test at
Screening, a negative urine pregnancy test at Baseline (Day -1 to Day 1), and must use
acceptable contraception*.
*Acceptable contraception methods are restricted to surgical sterilization (bilateral
tubal ligation) or successful Essure placement (permanent, non-surgical, non-hormonal
sterilization with documented radiological confirmation at least 90 days after the
procedure), use of long-acting reversible contraceptive devices (progestin-releasing
subdermal implants [Nexplanon and Implanon, Merck], copper intrauterine devices
[Paragard, Teva], and levonorgestrel-releasing intrauterine devices [Mirena, Bayer;
Skyla, Bayer; Liletta, Allergan/Medicines360]), licensed hormonal products such as
injectables or oral contraceptives, barrier methods such as condoms or diaphragms with
spermicidal agents, and abstinence from sexual intercourse with a male partner.
Subjects must have used the above-listed method for a minimum of 30 days prior to the
first dose of study drug and be willing to use the method for at least 30 days after
the final dose of study drug.
5. Male subjects* whose partners are of childbearing age or pregnant must be willing to
use condoms during the study and through the Day 3 follow-up call.
*including men who have had vasectomies
6. Able to abstain from alcoholic beverages within 48 hours before Baseline (Day -1 to
Day 1) and throughout the Treatment Phase.
7. Able to abstain from caffeine use within 7 days before Baseline (Day -1 to Day 1) and
throughout the inpatient period.
8. Willing to remain in Duke Early Phase Research Unit (DEPRU) during the Baseline and
Treatment Phases.
9. Have a high probability for compliance and completion of the trial.
10. Sign a dated, witnessed, written Informed Consent Form (ICF).
11. Have adequate venous access for infusions and blood draws.
Exclusion Criteria:
1. Any surgical or medical condition that in the opinion of the investigator could
interfere with drug absorption, distribution, metabolism, or excretion.
2. Any surgical or medical condition that in the opinion of the investigator may place
the subject at increased risk while participating in the trial.
3. History or presence of cardiovascular disease including coronary artery disease and
chronic hypertension (systolic pressure > 140 mmHg or diastolic pressure > 90 mmHg).
4. Abnormal Electrocardiogram (ECG) at screening, as determined by the investigator to be
clinically significant.
5. History or presence of renal impairment or chronic renal disease.
6. History or presence of liver disease (Alanine Aminotransferase (ALT), Aspartate
Aminotransferase (AST), or total bilirubin above the upper limit of normal).
7. History or presence of chronic pulmonary disease, including asthma, requiring use of
medication in the year before screening.
8. History of intolerance or hypersensitivity to phosphonic acid derivative antibiotics
or any of its constituents (i.e., oral or intravenous fosfomycin).
9. Have cancer or have a history of cancer within the past 5 years, with the exception of
non-melanomatous skin cancer, treated, without evidence of recurrence.
10. Any medical condition that prevents a subject from undergoing bronchoscopy with
bronchoalveolar lavage (BAL).
11. Serum creatinine above the upper limit of normal, or estimated creatinine clearance
(CrCl) < 60 mL / min as determined by Cockcroft-Gault equation*.
*Cockcroft-Gault equation where age is in years, weight is in kilograms, and serum Cr
is in mg/dL units: Males: CrCl (mL / min) = (140 - age) x Weight / (72 x Cr) Females:
CrCl (mL / min) = [(140 - age) x Weight / (72 x Cr)] x 0.85
12. History of regular alcohol consumption within 6 months of Baseline (Day -1 to Day 1)*.
*History of regular alcohol consumption is defined as an average weekly intake of > 14
drinks for males or > 7 drinks for females. One drink is equivalent to 12 g of
alcohol: 12 ounces (360 mL) of beer, 5 ounces (150 mL) of wine, or 1.5 ounces (45 mL)
of 80 proof distilled spirits.
13. History of > / = 10 pack-years smoking, or history of any nicotine use* in the 6
months before Baseline (Day -1 to Day 1)** or positive urinine cotinine screen at
Basline (Day -1 to Day 1).
*Including cigarettes, pipe, cigar, chewing tobacco, nicotine patch.
**A positive urine cotinine at screening is allowed if negative at baseline.
14. History of illicit drug use within 6 months of Baseline (Day -1 to Day 1)*. *Use of
cannabinoids within 1 month of Baseline (Day -1 to Day 1) is excluded, but other use
of cannabinoids within 6 months is permitted.
15. Use of any prescription drugs, except acceptable contraception methods listed above,
within 30 days of Baseline (Day -1 to Day 1).
16. Involvement in other investigational studies of any type (drugs, devices, procedures)
within 30 days of Baseline (Day -1 to Day 1).
17. Blood or blood products donation within 30 days of Baseline (Day -1 to Day 1).
18. Planning egg or sperm donation any time before Day 3 follow-up call.
19. Use of any non-prescription medications, vitamins, consumption > 2 times/week of
products containing genuine licorice, caffeine, or dietary or herbal supplements
within 7 days of Baseline (Day -1 to Day 1)*.
*Excluded from this list is intermittent use of acetaminophen at doses < / = 2 g /
day. Herbal supplements must be discontinued 7 days before the initial dose of study
drug on Day 1.
20. Presence of any acute illness, including febrile illness with temperature > 37.8
degrees Celsius (> 100.0 degrees Fahrenheit), within 7 days of Baseline (Day -1 to Day
1).
21. Currently pregnant or breastfeeding as determined by subject report.
22. Positive tests for human immunodeficiency virus (HIV) 1 and 2 antibodies, hepatitis B
surface antigen (HBsAg), or hepatitis C virus (HCV) antibody.
23. Positive urine drug or positive breathalyzer test for alcohol at Screening or Baseline
(Day -1 to Day 1) or positive cotinine at Baseline (Day -1 to Day 1).
24. Weight loss or gain of > 10% within 30 days of Baseline (Day -1 to Day 1).
25. Any laboratory value at screening or enrollment that is Grade 2 or more. A laboratory
value that is Grade 1 will be allowed if not considered to be clinically significant
by the investigator*.
- Excluded from this list of permissible Grade 1 laboratory values are (ALT),
(AST), or Total bilirubin per Exclusion Criteria 6 and serum creatinine per
Exclusion Criteria #11; and serum electrolytes including sodium, potassium,
calcium, phosphorus and magnesium.
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-no
