Retapamulin Versus Linezolid in the Treatment of SITL and Impetigo Due to MRSA

This is a prospective, randomized, double-blind, double dummy, multicenter, comparative
study in subjects 2 months of age and older with SITL (including secondarily-infected
lacerations, sutured wounds and abrasions) or impetigo (bullous and non-bullous) due to
MRSA. A laceration or sutured wound cannot exceed 10 cm in length with surrounding erythema
not extending more than 2 cm from the edge of the lesion. Abrasions cannot exceed 100 cm2 in
total area, or up to a maximum of 2% total body surface area for subjects <18 years of age,
with surrounding erythema not extending more than 2 cm from the edge of the abrasion.
Subjects with impetigo can have up to 10 lesions and the infected lesion(s) must not be more
than 100 cm2 in area (or up to a maximum of 2% total body surface area for subjects <18
years of age), must not require surgical intervention and must be able to be appropriately
treated with a topical antibiotic.

There are five study visits occurring over a 17-19 day period. At the baseline visit (Visit
1, day 1), subjects will be randomized to receive retapamulin (plus oral placebo) or
linezolid (plus placebo ointment) in a 2:1 ratio. Retapamulin is applied twice daily for 5
days, and linezolid is dosed, depending on subject age, either twice or three times daily
for 10 days. The on-therapy, end of therapy and follow-up visits are staggered due to the
difference in duration of the treatment regimens. Subjects will be monitored and clinically
evaluated at all postbaseline visits.

Randomization will be center-based and stratified by age (<5 years, ≥5 to <12 years, ≥12
years), performed using an appropriate Interactive Voice Response System (IVRS), an
automated telephone system. The block size will remain confidential. Subjects are considered
to have completed the study if they meet all inclusion/exclusion criteria, are considered
compliant with study medication, and attend all study visits as defined by the protocol.

Inclusion Criteria:

- 2 months of age or older

- diagnosis of secondarily-infected traumatic lesion (SITL) or impetigo (bullous or
non-bullous)

- negative urine pregnancy test (females of childbearing potential)

- total skin infection rating scale (SIRS) score of at least 8, which must include a
pus/exudate score of at least 3

- subject or parent/legal guardian willing and able to comply with protocol

- written informed, dated consent, and written assent (if applicable)

Exclusion Criteria:

- previous hypersensitivity to pleuromutilins or oxazolidinones

- phenylketonuria or known hypersensitivity to aspartame

- secondarily-infected animal/human bite, or puncture wound

- abscess

- chronic ulcerative lesion

- underlying skin disease (eg, eczematous dermatitis) with secondary infection

- systemic signs and symptoms of infection

- skin infection not appropriate for treatment by a topical antibiotic (eg, extensive
cellulitis, furunculosis)

- subject requires surgical intervention for infection prior to study or likely will
during the study

- receipt of systemic antibacterial or steroid, or application of any topical
therapeutic agent directly to wound within 24 hours of entry into the study

- subject currently receiving adrenergic agents

- subject currently receiving serotonergic agents

- history of pseudomembranous colitis

- known, pre-existing myelosuppression, history of myelosuppression with linezolid use,
or receiving a medication that produces bone marrow suppression

- history of siezures

- history of severe renal failure and undergoing dialysis

- serious underlying disease that could be imminently life-threatening

- pregnant, breast feeding or planning a pregnancy, or not using accepted method of
contraception (females of childbearing potential or <1 year post-menopausal)

- use of another investigational drug within 30 days prior to entry into this study

- previously enrolled in this study

- fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase
insufficiency (for subjects <12 years of age receiving linezolid suspension)