Safety of Either a Single or Two IV Doses of Orbactiv in Subjects With ABSSSI

Clinical studies in adult subjects with ABSSSI have demonstrated that a single 1200-mg IV
dose of oritavancin was clinically non-inferior, well tolerated, and had a similar safety
profile to 7 to 10 days of IV vancomycin treatment.

The 1200-mg dose of oritavancin is the United States (US) approved therapeutic dose.

Subjects with ABSSSI will be enrolled in this study to obtain safety information of two
1200-mg IV infusions of oritavancin when administered one week apart. The safety information
will include the potential for antibody production following two 1200-mg IV infusions of
oritavancin.

This study will be a randomized, double-blind study. Subjects will be randomized to receive
either two doses of oritavancin or one dose of oritavancin and a single dose of placebo one
week apart in order to obtain safety information. This safety information will include
information regarding the potential for antibody production following one or two doses of
1200 mg oritavancin.

Inclusion Criteria:

- Diagnosis of ABSSSI (wound infections, Cellulitis/erysipelas, or cutaneous abscess)
suspected or confirmed to be caused by a Gram-positive pathogen requiring IV therapy

- Able to give informed consent and willing to comply with all required study
procedures

Exclusion Criteria:

- Infections associated with, or in close proximity to, a prosthetic device

- Severe sepsis or refractory shock

- Known or suspected bacteremia at time of screening

- ABSSSI due to or associated with any of the following:

- Infections suspected or documented to be caused by Gram-negative pathogens (i.e.,
human or animal bites, injuries contaminated with fresh or salt water, external
malignant otitis)

- Wound infections (surgical or traumatic) and abscesses with only Gram-negative
pathogens

- Diabetic foot infections (infection extending distal to the malleoli in a subject
with diabetes mellitus and peripheral neuropathy and/or vascular insufficiency or any
ulceration of their foot)

- Concomitant infection at another site not including a secondary ABSSSI lesion (e.g.,
septic arthritis, endocarditis, osteomyelitis)

- Infected burns

- A primary infection secondary to a pre-existing skin disease with associated
inflammatory changes such as atopic dermatitis, eczema, or hidradenitis suppurativa

- Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease
(arterial or venous)

- Any evolving necrotizing process (i.e., necrotizing fasciitis), gangrene, or
infection suspected or proven to be caused by Clostridium species (e.g., crepitance
on examination of the ABSSSI site and/or surrounding tissue(s) or radiographic
evidence of subcutaneous gas in proximity to the infection)

- Infections known to be caused by a Gram-positive organism with a vancomycin minimum
inhibitory concentration (MIC) >2 μg/mL or clinically failing prior therapy with
glycopeptides

- Catheter site infections

- Currently receiving chronic systemic immunosuppressive therapy such as chemotherapy
or prednisone (prednisone at non-immunosuppressive doses of ≤15 mg/day is permitted)

- Subjects who are likely to need treatment with IV unfractionated heparin sodium
within 48 hours after oritavancin administration

- Last known cluster of differentiation 4 (CD4) count <200 cells/mm3 in subjects with
known human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS)

- Neutropenia with absolute neutrophil count (ANC) <500 cells/mm3

- Significant or life-threatening condition (e.g., endocarditis) that would confound or
interfere with the assessment of safety

- Women who are pregnant or nursing, or who are of childbearing potential and unwilling
to use at least 2 acceptable methods of birth control: (e.g., prescription oral
contraceptives, contraceptive injections, contraceptive patch, intrauterine device,
barrier method(s) or male partner sterilization). Women ≥2 years postmenopausal or
surgically sterile are exempt from this exclusion

- History of immune-related hypersensitivity reaction to glycopeptides (such as
vancomycin, televancin, daptomycin, or dalbavancin) or any of their excipients. Note:
subjects who have had histamine-like infusion reactions to a glycopeptide are not
excluded

- Subjects unwilling to forego blood and/or blood product donation for at least 1 month
from initiation of oritavancin dose

- Treatment with investigational medicinal product within 30 days or 5 half-lives,
whichever is longer, before enrollment and for the duration of the study

- Investigational device present, or removed within 30 days before enrollment, or
presence of device-related infection

- Subjects who the investigator considers unlikely to adhere to the protocol, comply
with oritavancin administration, or complete the clinical study (e.g., unlikely to
survive 90 days from initiation of oritavancin dosing)

- Prior exposure to oritavancin alone or in combination with another product.