Evaluate Effects of Meropenem-Vaborbactam on QT/QTc in Healthy Volunteers

This Thorough-QT (TQT) study in healthy volunteers will be conducted in two phases. Phase One
(n=15) will be used to identify a safe supratherapeutic dose to be used in the TQT study
(Phase Two). Phase Two will be a randomized, placebo and positive-controlled, 4-way crossover
TQT study. Thirty-two subjects will receive all 4 of the following treatments in randomized
sequence.

1. meropenem-vaborbactam 4 g (meropenem 2 g- vaborbactam 2 g) therapeutic dose infused
intravenously over 3 hours

2. meropenem-vaborbactam supratherapeutic dose to be determined infused intravenously over
3 hours.

3. Placebo (normal saline) to match meropenem-vaborbactam volume infusion over 3 hours

4. Moxifloxacin 400 mg positive control (oral; open-label)

Inclusion Criteria:

1. Male or female subject between 18 and 55 years of age, inclusive, with a body mass
index (BMI) ≥18 to ≤33 kilogram (kg)/m2.

2. All women of child-bearing potential must agree to use an adequate method of
contraception during the study and for 30 days after the last dose. Accepted methods
of contraception include: mechanical products (e.g., intrauterine device) or
double-barrier methods (e.g., diaphragm, condoms, cervical cap) with spermicide or
hormonal contraceptives (i.e., oral, implanted or injectable contraceptive hormones)
or abstinence. Oral contraceptives must be used together with a second method of birth
control. If the female subject has a male partner who has had a vasectomy, one
additional form of medically acceptable contraception (condom or spermicide) must also
be used. The subject's understanding of this requirement must be documented by the
Investigator.

Males with female partners of childbearing potential must agree to use a highly
effective, medically acceptable form of contraception from the Screening period
through 30 days after the last dose. Males with female partners of childbearing
potential who themselves are surgically sterile (status post vasectomy) must agree to
use condoms with spermicide over the same period of time. Male subjects must agree to
practice the above birth control methods for 30 days after the final dose. Males must
agree to not donate sperm through 30 days after the final dose.

3. Stable health based on no clinically-significant findings on the medical history,
physical examination, or clinical laboratory test results at screening and prior to
study drug administration (as determined and documented by the Investigator).

4. Willing to comply with all study activities and procedures and provides written
informed consent prior to any study procedures

Exclusion Criteria:

1. Known hypersensitivity to beta-lactam antibiotics (including meropenem),
fluoroquinolone antibiotics (including moxifloxacin) or vaborbactam.

2. An uninterpretable or abnormal screening electrocardiogram (ECG) indicating a second
or third degree atrioventricular block, or any rhythm other than sinus rhythm that is
interpreted by the investigator to be clinically significant or one or more of the
following: QRS interval >110 milliseconds (ms); QTcF >430 ms (males) and >450 ms
(females); PR interval >200 ms; heart rate (HR) <50 beats per minutes (bpm); or >90
bpm.

3. History of risk factors for torsades de pointes, including unexplained syncope, known
long QT syndrome, heart failure, myocardial infarction, angina. Subjects will also be
excluded if there is a family history of long QT syndrome or Brugada syndrome or
unexplained sudden death.

4. Subject has any clinically relevant abnormalities, as determined by the Investigator,
in the laboratory results at Screening or admission of each study period

5. Serum potassium, serum magnesium, or albumin-corrected calcium lower than the lower
limit of normal for the reference lab at Screening or admission of each study period.
Calcium will be corrected for albumin using the formula: Corrected Calcium = (0.8 *
(Normal Albumin - Pt's Albumin)) + Serum Ca where Normal Albumin is 4.0 g/dL.

6. Hemoglobin and hematocrit lower than the lower limit of normal for the reference lab
at Screening.

7. Subject has an abnormal liver function tests: alanine aminotransferase [ALT],
aspartate aminotransferase [AST], or bilirubin greater than 1.2X the upper limits of
normal at Screening.

8. History of central nervous system (CNS) disorder including convulsions.

9. A sustained supine systolic blood pressure >140 mmHg or <90 mmHg or a supine diastolic
blood pressure >90 mmHg or <50 mmHg at Screening or Check in (Day -1). Blood pressure
may be retested once in the supine position. The blood pressure abnormality is
considered sustained if either the systolic or the diastolic pressure values are
outside the stated limits after 2 assessments, in which case the subject should not be
randomized.

10. Impaired renal function as evidenced by estimated glomerular filtration rate (eGFR)
<50.

11. Unstable cardiovascular disease, including recent myocardial infarction or cardiac
arrhythmia.

12. History of acquired immunodeficiency syndrome or history of a positive test result for
human immunodeficiency virus (HIV), hepatitis C virus (HCV) antibody, or hepatitis B
surface antigen (HBsAg) at Screening.

13. Positive drug, alcohol, or tobacco screen.

14. Clinically-significant illness, including viral syndromes within 3 weeks of dosing.

15. Women who are pregnant (or planning to become pregnant within the next 6 months) or
currently breastfeeding. A negative serum pregnancy test is required before enrolling
in the study.

16. Participation in another investigational drug or device study or treated with an
investigational drug within 30 days or 5 half lives, whichever is longer, before
dosing. Any subject who participated in Phase One of this trial is not eligible to
participate in Phase Two.

17. Consumed more than 28 units of ethanol per week at any time in the 6 months before
dosing (1 unit of ethanol is equivalent to 8 ounces of beer, 4 ounces of wine, or 1
ounce of spirits) or history of alcoholism and/or drug/chemical abuse.

18. Use of prescription medications (with the exception of oral contraceptives and hormone
replacement therapy), including nonsteroidal anti-inflammatory drugs or sucralfate and
medications known to prolong the QT/QTc interval or natural health products/herbal
preparations within 14 days or 5 half lives (whichever is longer) before study drug
dosing, or use of an over-the-counter (OTC) medication (excluding acetaminophen),
vitamins, or supplements (including omega-3 fish oils) within 7 days before study drug
dosing.

19. Use of alcohol , caffeine , or xanthine containing products, Seville oranges (sour),
grapefruit, or grapefruit juice, within 72 hours before study drug dosing.

20. Current use or has used tobacco- or nicotine-containing products (e.g., cigarettes,
cigars, chewing tobacco, snuff, etc.) 30 days before study drug dosing.

21. Strenuous activity (e.g., sports) from 96 hours (4 days) prior to entry into the
clinical research unit and throughout the study (until the final follow-up call is
conducted).

22. Donated more than 500 milliliter (mL) of blood or significant blood loss within 60
days prior to signing the informed consent form.

23. Any other medical, psychological, or social condition that, in the opinion of the
principal investigator or the medical monitor, would prevent the subject from fully
participating in the study, would represent a concern for study compliance, or would
constitute a safety concern to the subject.

24. An employee of the investigator or study center with direct involvement in the
proposed study or other studies under the direction of that investigator or study
center, as well as a family member of the employee or investigator.