Eligibility Details:
Inclusion Criteria:
1. Provide a signed and dated written informed consent.
2. Be able to understand and willing to comply with study procedures, restrictions, and
requirements, as determined by the Principal Investigator (PI).
3. Male and female volunteers aged 18 to 45 years inclusive.
4. Suitable veins for cannulation or repeated venipuncture.
5. Subject must be in good general health as judged by the investigator as determined by
medical history, vital signs*, body mass index (BMI) and body weight**, clinical
laboratory values***, and physical examination (PE).
*Oral temp <38.0 degrees Celsius/100.4 degrees Fahrenheit; pulse 50 to 100 bpm;
systolic blood pressure 90 to 140 mm Hg, and diastolic blood pressure 55 to 90 mmHg.
**BMI between 19-33 kg/m^2 and body weight > / = 50 kg
***Clinical chemistry, hematology, coagulation and urinalysis results within the
clinical laboratory reference ranges; clinical laboratory values outside these ranges,
if considered by the site investigator to be clinically insignificant, are also
acceptable
6. Sexually active female subjects must be of non-childbearing potential**** or must use
a highly effective method of birth control*****.
****Non-childbearing potential is defined as being post-menopausal for at least 18
months or surgically sterile via hysterectomy, bilateral oophorectomy, or tubal
sterilization.
*****Sexually active female subjects of childbearing potential must avoid becoming
pregnant by using one of the following acceptable methods of birth control for 30 days
prior to study product dosing and must be maintained for 30 days after last dose of
study product: Intrauterine contraceptive device; OR Approved hormonal contraceptives
(such as birth control pills, skin patches, Implanon(R), Nexplanon(R), DepoProvera(R)
or NuvaRing(R)); OR Birth control must be captured on the appropriate data collection
form.
7. Sexually active male subjects must be vasectomized or agree to use barrier
contraception (condom with spermicide) from first dose of study product until 30 days
following the last dose of study product.
8. Nonsmokers defined as abstinence from cigarette smoking or use of nicotine-containing
products for 6 months prior to enrollment into the study.
Exclusion Criteria:
1. History of any clinically significant (CS) disease or disorder, medical/surgical
procedure, or trauma within 4 weeks prior to the first administration of study
product(s)*.
*In the opinion of the PI, may either put the volunteer at risk because of
participation in the study, or influence the results or the volunteer's ability to
participate in the study
2. History or presence of gastrointestinal, hepatic, or renal disease, or any other
condition known to interfere with absorption, distribution, metabolism, or excretion
of drugs.
3. Known history of a clinically important allergy/hypersensitivity to AVI, any
monobactam, any beta-lactam and/or L-arginine.
4. Receipt of probenecid or furosemide within 14 days prior to study enrollment.
5. Receipt of any antibiotics within 14 days prior to study enrollment.
6. Receipt of prescription medications (except birth control pills or hormone replacement
in females) within 14 days prior to study enrollment, unless in the opinion of site
investigator the medication will not interfere with the study procedures or impact
subject safety.
7. Receipt of non-antibiotic medications that interacts with OAT3** within 14 days prior
to study enrollment.
**Adefovir, Anagliptin, Baricitinib, Cefaclor, Cimetidine, Ciprofloxacin (Systemic),
Clofarabine, Eluxadoline, Empagliflozin, Furosemide, Ketoprofen, Methotrexate,
Mycophenolate, PEMEtrexed, Penicillin G (Parenteral/Aqueous), Penicillin G Benzathine,
Penicillin G Procaine, Penicillin V Benzathine, Penicillin V Potassium, Zidovudine
8. Receipt of herbal and dietary supplements (including St. John's Wort) within 14 days
prior to study enrollment.
9. ALT or AST laboratory value above the ULN as defined in the toxicity table.
10. Prolonged QTcF (> 450 msec) or shortened QTcF (< 340 msec) or family history of long
QT syndrome. Any clinically important abnormalities in rhythm, conduction, or
morphology of resting ECG***.
***Abnormalities that may interfere with interpretation of QTc interval changes per
the medical judgment of the PI.
11. Any positive result on screening for human immunodeficiency virus (HIV) serum
hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) antibody.
12. Creatinine clearance equal or less than 80 mL/minute (measured by Cockcroft-Gault
method).
13. History of Clostridium difficile infection in past 90 days.
14. Known or suspected history of drug or alcohol abuse within the last 5 years, as judged
by the PI.
15. Positive screen for drugs of abuse, cotinine (nicotine), or alcohol at screening and
at admission to the study site prior to the first administration of the study
products(s).
16. Received a new chemical entity (compound not approved for marketing) or participated
in a study that included drug treatment within 1 month of the first dose of study
product(s) for study ****.
****Period of exclusion begins at the time of the last visit of the prior study.
Note: subjects consented and screened, but not dosed in this study or a previous Phase
I study will not be excluded.
17. Previous participation in the present study.
18. Involvement in the planning and/or conduct of the study.
19. Any ongoing/recent (during screening) medical complaints that may interfere with
analysis of study data or are considered unlikely to comply with study procedures,
restrictions, and requirements *****.
*****Judgment by the PI that the subject should not participate in the study.
20. Known history of past or current epilepsy or seizure disorders, excluding febrile
seizures of childhood.
common.study.methods.has-drugs-yes
common.study.methods.is-healthy-no
