A Trial to Evaluate the Pharmacokinetics and Safety of AVYCAZ(R) in Combination With Aztreonam

Inclusion Criteria

• Provide a signed and dated written informed consent.
• Be able to understand and willing to comply with study procedures, restrictions, and requirements, as determined by the Principal Investigator (PI).
• Male and female volunteers aged 18 to 45 years inclusive.
• Suitable veins for cannulation or repeated venipuncture.
• 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 / = 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

• 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.

• 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.
• Nonsmokers defined as abstinence from cigarette smoking or use of nicotine-containing products for 6 months prior to enrollment into the study.

Exclusion Criteria

• 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

• History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Known history of a clinically important allergy/hypersensitivity to AVI, any monobactam, any beta-lactam and/or L-arginine.
• Receipt of probenecid or furosemide within 14 days prior to study enrollment.
• Receipt of any antibiotics within 14 days prior to study enrollment.
• 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.
• 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

• Receipt of herbal and dietary supplements (including St. John's Wort) within 14 days prior to study enrollment.
• ALT or AST laboratory value above the ULN as defined in the toxicity table.
• 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***.

***Ab