Study of the Safety and Local Tolerability of Intranasal Gel Formulations of XF-73

This is a Phase I, multi-center, clinical study of XF-73 to evaluate the local (nasal)
safety and tolerability of a modified, thinner, lower viscosity formulation of intranasal
XF-73 in healthy male and female subjects. In addition, the potential for systemic
absorption of XF-73 in the modified, thinner, lower viscosity and the previously
investigated thicker, higher viscosity formulations and their decolonization efficacy in
comparison to placebo will be evaluated. Both parts of the study will be double-blinded, and
Part 2 will also be placebo-controlled. Study subjects will be healthy volunteers, male or
female, aged 18 - 45 years. The study will be conducted in two distinct parts. In Part 1 of
the study 8 healthy male and female subjects, aged 18 to 45 years, will be in two groups of
four per formulation will have a study duration of up to 36 days. All subjects will receive
intranasal applications of 5,15-bis-[4-(3-Trimethylammonio-propyloxy)-phenyl]-porphyrin
dichloride (XF-73). In Part 2 only, subjects will also need to be confirmed as persistent
nasal SA carriers (n = 48). (Persistent SA carriage is defined by 3 separate, SA positive
cultures from nasal swabs: the first taken at Pre-Screening no more than 12 weeks (84 days).
Administration will last five days, being three times a day on Day 1, then twice a day
thereafter. Primary objective is to establish the safety and tolerability of two
concentrations of a modified thinner, lower viscosity nasal formulation of XF-73 and to
compare them to a previously investigated, thicker, higher viscosity formulation. Secondary
objectives are to establish whether there is any potential systemic exposure following
administration of the two nasal formulations of XF-73 and to evaluate the
anti-staphylococcal efficacy of two concentrations of a lower and one of a thicker, higher
viscosity nasal formulation of XF-73.

Inclusion Criteria:

1. Normal, healthy male or female subjects aged between 18 and 45 years inclusive.

2. For Part 2 only: Normal healthy subjects confirmed to be persistent SA carriers
(NOTE: Persistent SA carriage is defined by 3 separate, SA (Staphylococcus aureus)
positive cultures from nasal swabs: the first taken at Pre-Screening no more than 12
weeks (84 days) prior to first dosing, a confirmatory swab taken at Screening at
least 7 days after Pre-Screening and a final confirmation swab taken on Admission, a
day before dosing and at least 7 days after screening. Subjects may be dosed with
only two positive swabs while awaiting the result of the third swab obtained on
Admission, but dosing will be discontinued in subjects whose Admission swab is found
to be negative for SA.

3. Subject must be healthy, in the opinion of the Investigator, as determined by medical
history (MH), physical examination (PE), normal nasal examination, and vital signs
(VS).

4. Subject's 12-lead electrocardiogram (ECG) must be normal or abnormal not clinically
significant as reported by the overreading cardiologist.

5. Subject's clinical laboratory results at Screening must be within the reference range
or expanded range.Subjects may undergo a repeat screening test of out-of-range
analytes at the discretion of the investigator to confirm a plausible alternative
explanation that will be indicated in the source documentation.

6. Any subject having laboratory values outside of the reference range or expanded range
at Day -1 but were within the reference or expended range at screening may be
enrolled on study. Abnormal urine dipstick values for blood/hemoglobin, nitrite, and
leukocyte esterase will not be exclusionary if a microscopic examination of the urine
on the same sample or the most recent sample obtained prior to dosing is within the
reference or expanded range. Laboratory values outside the reference or expanded
range will be assigned to toxicity grade.

7. Subjects who are able and willing to provide written informed consent to participate
in the study.

8. Subject agrees to comply with all study requirements.

9. All female subjects of childbearing potential must have a negative serum and urine
pregnancy test at Screening and Admission respectively.

10. Subjects who have a body mass index (BMI) >/= 18.5 kg/m^2 and
11. Subject agrees not to participate in another clinical trial at any time during the
study period.

Exclusion Criteria:

1. Female subjects who are pregnant or who are lactating.

2. Heterosexually active females of child-bearing potential, defined as being
physiologically capable of becoming pregnant, unless they agree to use two of the
following acceptable methods of contraception throughout their participation in the
study and for at least 12 weeks after the final dose: (a) established use of oral,
injected or implanted hormonal contraception, (b) intrauterine Device (IUD or Coil),
(c) a female barrier method (diaphragm or cervical/vault cap) and/or (d) condom plus
spermicidal cream/gel. Women who are not sexually active (abstinent) but become
active must use two of the listed contraceptive methods.

3. Heterosexually active males unless they agree to use two concomitant acceptable
methods of contraception throughout their participation in the study and for at least
12 weeks after receiving their final dose of study medication (examples include:
vasectomy combined with latex condom with spermicide, latex condom with spermicide
combined with a female partner who practices an acceptable method of contraception as
indicated above); Men who are not sexually active (abstinent) but become active must
use two of the listed contraceptive methods. Subjects who currently have or have had
any acute illness within the past two weeks.

4. Subjects who currently have or have had within the past two weeks a poorly controlled
chronic illness(anemia, thrombocytopenia, or coagulation disorders), cancer,
infection, or any other clinically significant disorder.

5. Subjects who currently have or have had an autoimmune disease.

6. Subjects who have had within the past two weeks a symptomatic upper respiratory tract
infection, nasopharyngitis, influenza or condition involving increase in nasal
secretion such as seasonal or chronic, allergic rhinitis. Additionally, any subject
with history of atopy/allergies within the past 30 days will be excluded.

7. Subjects who have had been diagnosed with a concussion within the past two years.

8. Subjects with a history of serious psychiatric condition (depression, bipolar
disorder, schizophrenia, suicidal ideation, or suicide attempts) or receiving two
concomitant medications for the treatment of a psychiatric disorder or hospitalized
for the treatment of a serious psychiatric disorder within six months of
participation in the study.

9. Subjects with known skin photosensitivity.

10. Subjects with a personal or family history of porphyria.

11. Subjects with any open wound, lesion, inflammation, erythema, or infection affecting
the nostrils, nose, upper lip, and area of skin close to the nose, including herpes
simplex lesions and discoid lupus.

12. Subjects with a history of abnormal bleeding, bruising, frequent nosebleeds, or the
diagnosis of von Willebrand disease.

13. Subjects with nasal polyps or significant anatomical nasal abnormality. Patients with
deviated septa will be allowed in the study, provided the principal investigator does
not deem a deviation to be of significant medical consequence. An ENT(Ear, Nose and
Throat) specialist will be available for consult as needed.

14. Subjects with a history of nasal surgery, including cauterization, in the last 6
months.

15. Subjects with a history of multiple episodes [>3] of epistaxis within the 12 months
prior to screening.

16. Subjects with in situ nasal jewelry or open nasal piercings.

17. Subjects with a known clinically significant history of atopy or hypersensitivity to
any drug or latex or to ingredients of the nasal gel (such as benzalkonium chloride
or other quaternary ammonium disinfectants) or to drugs related to XF-73.

18. Subjects known to have dermal sensitivity to chlorhexidine gluconate (CHG).

19. Subjects who have smoked within the month prior to screening.

20. Subjects who have been treated with or have taken any prescribed or over-the-counter
medication daily for the last 14 days, with the exception of hormonal contraceptives
or hormone replacement therapy.

21. Subjects who have taken or used topical or systemic antibiotics within the month
prior to screening.

22. Subjects who have received an immunization within 30 days prior to screening.

23. Subjects with a history of drug or alcohol abuse in the last 12 months or who have a
positive urine drug test for substances of abuse (amphetamines, barbiturates,
benzodiazepines, cannabinoids, cocaine metabolites, opiates, phencyclidine [PCP]) or
alcohol.

24. Subjects who are known to have serum hepatitis, or who are carriers of the hepatitis
B surface antigen(HBsAg) or hepatitis C (HCV) antibody, or who have a positive result
to the test for human immunodeficiency virus (HIV) antibodies.

25. Subjects who have participated in a drug or vaccine clinical trial within the last
month.

26. Subjects who have been exposed to XF-73 as part of a previous clinical trial.

27. Presence of any other condition or laboratory result that, in the opinion of the
investigator would jeopardize the safety or rights of a subject participating in the
trial or would render the subject unable to comply with the protocol.