The Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of FAST PV and mGFR Technology™

For Cohorts 1 and 2, administration of the study drug will occur within 21 days of screening.
Eligible subjects/patients will be admitted to the clinical research unit (CRU) on Day -1, at
which time assessments will be performed, and results from both screening and Day -1
(inclusion/exclusion criteria, body weight, height [screening only], body mass index [BMI],
medical and surgical history, physical examination, vital signs and pulse oximetry, 12 lead
ECG, clinical laboratory tests, renal function assessment, follicle-stimulating hormone [FSH;
screening only] and pregnancy test [females only], and urine drugs of abuse and alcohol
screen) will be reviewed to confirm eligibility.

For Cohorts 3 and 4, administration of the study drug will occur within 21 days of screening.
Eligible subjects/patients will be admitted to the CRU on Day 1, at which time assessments
will be performed and results from both screening and predose administration testing
(inclusion/exclusion criteria, body weight, height [screening only], BMI, medical and
surgical history, physical examination, vital signs and pulse oximetry, 12 lead ECG, clinical
laboratory tests, renal function assessment, FSH and pregnancy test [screening only], and
urine drugs of abuse and alcohol screen) will be reviewed to confirm eligibility.

Cohort 1:

Eligible subjects will receive a single dose of VFI followed 130 minutes later by a 350 mL
infusion of 5% albumin up to maximum volume of 7 mL/kg over 30 minutes on Day 1. Subjects
will remain resident in the CRU for at least 24 hours after VFI administration for safety,
PK, and PD assessments. Subjects will return to the CRU for an end-of-study (EOS) visit on
Day 21 (± 1 day).

Cohort 2:

Eligible subjects will receive a dose of VFI followed 160 minutes later by a single dose of
Iohexol on Day 1 and a second dose of VFI 24 hours following the initial dose of VFI.
Subjects will remain resident in the CRU for at least 24 hours after the second VFI
administration for safety, PK, and PD assessments. Subjects will return to the CRU for
follow-up visits on Days 5 (± 1 day), 9 (± 1 day), and 16 (± 1 day) and an EOS visit on Day
22 (± 1 day).

Cohorts 3 and 4:

Eligible patients will receive a single dose of VFI followed 160 minutes later by a single
dose of Iohexol on Day 1. Patients will remain in the CRU through the 12-hour sample
collection after VFI administration for safety, PK, and PD assessments. . Patients will stay
at a local hotel near the CRU and will return to the CRU on Day 2 for the 24-hour sample
collection. Patients will return to the CRU for follow-up visits on Days 4 (± 1 day), 8 (± 1
day), and 15 (± 1 day) and an EOS visit on Day 21 (± 1 day).

Inclusion Criteria:

All Subjects/Patients:

1. Males or females ≥ 18 and ≤ 75 years of age.

2. Females must be of non-childbearing potential (eg, postmenopausal [defined as
cessation of regular menstrual periods for at least 1 year confirmed by
follicle-stimulating hormone (FSH) test] or surgically sterile by hysterectomy,
bilateral oophorectomy, or tubal ligation [documentation required] or be using a
medically acceptable form of birth control [eg, a barrier method, intrauterine device,
or hormonal contraception]) from screening until 30 days after last dose.

3. Males who are sexually active and whose partners are females of childbearing potential
must agree to practice abstinence or use condoms from screening through 90 days after
administration of the last dose of study drug, and their partners must be willing to
use a medically acceptable method of contraception (a barrier method, intrauterine
device, or hormonal contraception) from screening through 90 days after administration
of the last dose of study drug.

4. Males must agree to not donate sperm from screening through 90 days after
administration of the last dose of study drug.

5. Subjects must be able to communicate effectively with the study personnel.

6. Subjects must be informed of the nature and risks of the study and give written
informed consent prior to screening.

7. Body mass index ≥ 18.0 and ≤ 40.0 kg/m2, and body weight ≥ 40 kg at screening and CRU
admission.

BMI = weight (kg)/(height [m])2

Subjects with Normal Renal Function (Cohorts 1 and 2):

8. Subjects must have an eGFR (calculated using the CKD-EPI Equation) ≥ 60 mL/min/1.73 m2
consistent with the National Kidney Foundation stages 1 and 2 of CKD.

9. Subjects must be otherwise healthy and without clinically significant abnormalities as
assessed by review of medical and surgical history, physical examination, vital signs
measurement, pulse oximetry, ECG, and clinical laboratory evaluations conducted at
screening and CRU admission. A single repeat measurement/test may be performed, at the
discretion of the physician, to confirm vital signs, pulse oximetry, ECG, and clinical
laboratory tests abnormalities (ie, to confirm that a subject is eligible).

Patients with Renal Impairment (Cohorts 3 and 4):

10. Patients in Cohort 3 must have an eGFR (calculated using the CKD-EPI Equation) ≥ 30
and < 60 mL/min/1.73 m2 consistent with the National Kidney Foundation stages 3a and
3b of CKD.

11. Patients in Cohort 4 must have an eGFR (calculated using the CKD-EPI Equation) ≥ 15
and < 30 mL/min/1.73 m2 consistent with the National Kidney Foundation stage 4 of CKD.

12. Patients may have clinical, ECG, and clinical laboratory findings consistent with
their degree of renal dysfunction as assessed by review of medical and surgical
history, physical examination, vital signs measurement, pulse oximetry, ECG, and
clinical laboratory evaluations conducted at screening and CRU admission. A single
repeat measurement/test may be performed, at the discretion of the physician, to
confirm vital signs, pulse oximetry, ECG, and clinical laboratory tests abnormalities
(ie, to confirm that a subject is eligible).

Exclusion Criteria:

All Subjects/Patients:

1. Female subject/patient is pregnant or breastfeeding.

2. History or presence of conditions which, in the judgment of the investigator, are
known to interfere with the distribution, metabolism, or excretion of drugs.

3. History or presence of conditions that may place the subject at increased risk as
determined by the investigator.

4. History of surgery or major trauma within 12 weeks of screening, or surgery planned
during the study.

5. History of alcohol abuse, illicit drug use, significant mental illness, physical
dependence to any opioid, or any history of drug abuse or addiction within 6 months of
screening.

6. Systolic blood pressure (BP) < 90 or > 160 mmHg or diastolic BP < 50 or > 100 mmHg
measured after the subject has been resting quietly in a supine position or in the
most recumbent position possible for at least 5 minutes at screening or CRU admission.
A single repeat measurement may be performed to confirm vital signs abnormalities (ie,
to confirm that a subject is eligible).

7. Heart rate (HR) < 40 or > 105 beats per minute (bpm) measured on ECG after the subject
has been resting quietly in a supine position or in the most recumbent position
possible for at least 5 minutes at screening or CRU admission. A single repeat
measurement may be performed to confirm ECG abnormalities (ie, to confirm that a
subject is eligible).

8. Has taken other investigational drugs or participated in any clinical study within 30
days or 5 half-lives of the investigational drug's PK, PD, or biological activity,
whichever is longer, prior to first dose of study drug in this study.

9. Prior exposure to VFI or known allergy to dextrans.

10. History of any clinically significant allergic or negative reactions, side effects, or
anaphylaxis to iodine, dyes, shellfish, isotopes, or dextran molecules.

11. Significant blood loss (> 450 mL) or has donated 1 or more units of blood or plasma
within 6 weeks prior to study participation.

12. Positive screen for human immunodeficiency virus (HIV)-1 or HIV-2 antibodies,
hepatitis B virus surface antigen (HBsAg), or hepatitis C virus (HCV) antibody.

13. Diagnosis of acquired immune deficiency syndrome (AIDS).

14. History of nephrectomy or kidney transplant.

15. History of liver disease or screening liver function tests which exceed 2 × the upper
limit of normal (ULN) or an albumin value of < 3 mg/dL.

16. International normalized ratio (INR) > 1.5 × ULN or a platelet count < 50,000.

17. Presence of significant hemodynamic instabilities.

18. Loss of Limb- as this alters the validity of eGFR and estimated PV equations.

19. Any other condition or prior therapy that, in the investigator's opinion, would make
the subject unsuitable for the study, or unable or unwilling to comply with the study
procedures.

20. Involved in the planning or conduct of this study.

21. Inability to tolerate venipuncture or poor venous access.

22. Unwilling to abstain from alcohol from 24 hours prior to admission until discharge
from the CRU.

23. Unwilling to abstain from strenuous activity (as assessed by the investigator) from 72
hours prior to admission until discharge from the CRU.

24. Unwilling or unlikely to comply with the requirements of the study.

Subjects with Normal Renal Function (Cohorts 1 and 2):

25. Positive urine drugs of abuse or alcohol screen.

26. Use of prescription medications or any drugs that induce or inhibit study drug
specific CYP(s) within 14 days or 5 half-lives, whichever is longer, of administration
of the first dose of study drug.

27. Use of over the-counter (OTC) drugs (including herbal preparations) within 7 days or 5
half lives, whichever is longer, prior to administration of the first dose of study
drug.

Patients with Renal Impairment (Cohorts 3 and 4):

28. Clinically significant ongoing bleeding, changing hemoglobin, or experienced
significant blood loss within 2 weeks prior to administration of the first dose of
study drug.

29. Positive urine drugs of abuse (except for prescribed medications) or alcohol screen.

30. Use of anticoagulants and nonsteroidal anti-inflammatory drugs within 3 days prior to
administration of the first dose of study drug.

31. Use of inotropes or vasopressors.

32. Any other condition or prior therapy that, in the investigator's opinion, is likely to
deteriorate.