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

Condition(s) targeted: Impetigo; Secondarily-infected Traumatic Lesions

Intervention: Linezolid (Drug); Retpamulin Ointment, 1% (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: GlaxoSmithKline

Official(s) and/or principal investigator(s):
GSK Clinical Trials, Study Director, Affiliation: GlaxoSmithKline

Overall contact:
US GSK Clinical Trials Call Center, Phone: 877-379-3718

The purpose of this study is to provide further evidence of the clinical and bacteriological efficacy of retapamulin in the treatment of subjects with SITL or impetigo due to MRSA. Subjects aged 2 months and older will be treated with either topical retapamulin for 5 days or oral linezolid for 10 days. The primary endpoint is the clinical response at follow-up (7-9 days after the end of therapy) in subjects who have a MRSA infection at baseline. The primary population is the per-protocol MRSA population. It is anticipated that approximately 500 subjects may be enrolled in order to obtain approximately 105 subjects who have a baseline MRSA infection.

Official title: A Randomized, Double-Blind, Double Dummy, Comparative, Multicenter Study to Assess the Safety and Efficacy of Topical Retapamulin Ointment, 1%, Versus Oral Linezolid in the Treatment of Secondarily-Infected Traumatic Lesions and Impetigo Due to Methicillin-Resistant Staphylococcus Aureus

Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Parallel Assignment, Safety/Efficacy Study

Primary outcome: Clinical response at follow-up in subjects with MRSA as the baseline pathogen

Secondary outcome:

Microbiological response at follow-up in subjects with MRSA as the baseline pathogen

Clinical response at follow-up in all subjects

Microbiological response at follow-up in all subjects with a baseline pathogen

Clinical outcome at end of therapy in subjects with MRSA as the baseline pathogen

Microbiological outcome at end of therapy in subjects with MRSA as the baseline pathogen

Clinical outcome at end of therapy in all subjects

Microbiological outcome at end of therapy in all subjects with a baseline pathogen

Therapeutic response (combined clinical and microbiological response) at follow-up

Detailed description: 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.

Minimum age: 2 Months. Maximum age: N/A. Gender(s): Both.

Criteria:

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)

US GSK Clinical Trials Call Center, Phone: 877-379-3718

GSK Investigational Site, Birmingham, Alabama 35235, United States; Not yet recruiting
William H Johnston, Principal Investigator

GSK Investigational Site, Anniston, Alabama 36207, United States; Recruiting
Almena L Free, Principal Investigator

GSK Investigational Site, Jonesboro, Arkansas 72401, United States; Not yet recruiting
Stephen C Golden, Principal Investigator

GSK Investigational Site, Paragould, Arkansas 72450, United States; Not yet recruiting
Dwight Williams, Principal Investigator

GSK Investigational Site, Little Rock, Arkansas 72202, United States; Not yet recruiting

GSK Investigational Site, Bentonville, Arkansas 72172, United States; Recruiting
Bryan M Harvey, Principal Investigator

GSK Investigational Site, Bell Gardens, California 90201, United States; Recruiting
Galal N Salem, Principal Investigator

GSK Investigational Site, Huntington Beach, California 92647, United States; Recruiting
Paul Y Qaqundah, Principal Investigator

GSK Investigational Site, Bakerfield, California 93301, United States; Recruiting
Tonny Tanus, Principal Investigator

GSK Investigational Site, Long Beach, California 90813, United States; Recruiting
Robert D Eyzaguirre, Principal Investigator

GSK Investigational Site, Roseville, California 95661, United States; Recruiting
Mark A King, Principal Investigator

GSK Investigational Site, Sacramento, California 92585, United States; Recruiting
Ronald Sockolov, Principal Investigator

GSK Investigational Site, Colorado Springs, Colorado 80909, United States; Recruiting
Gary Tarshis, Principal Investigator

GSK Investigational Site, Atlantis, Florida 33462, United States; Recruiting
Larry M Bush, Principal Investigator

GSK Investigational Site, St. Petersburg, Florida 33710, United States; Recruiting
Jeffrey A Hirschfield, Principal Investigator

GSK Investigational Site, West Palm Beach, Florida 33401, United States; Recruiting
Kenneth Beer, Principal Investigator

GSK Investigational Site, Pensacola, Florida 32504, United States; Not yet recruiting
Barbara H Wade, Principal Investigator

GSK Investigational Site, Fort Lauderdale, Florida 33308, United States; Recruiting
Anthony LaMarca, Principal Investigator

GSK Investigational Site, Macon, Georgia 31217, United States; Not yet recruiting
David J Cohen, Principal Investigator

GSK Investigational Site, Savannah, Georgia 31406, United States; Not yet recruiting
Maria Mascolo, Principal Investigator

GSK Investigational Site, Columbus, Georgia 31904, United States; Recruiting
Joseph G Surber, Principal Investigator

GSK Investigational Site, Honolulu, Hawaii 96814, United States; Recruiting
Francis Pien, Principal Investigator

GSK Investigational Site, Honolulu, Hawaii 96813, United States; Recruiting
Alan Tice, Principal Investigator

GSK Investigational Site, Overland Park, Kansas 66215, United States; Recruiting
Bruce H Short, Principal Investigator

GSK Investigational Site, Louisville, Kentucky 40217, United States; Completed

GSK Investigational Site, New Orleans, Louisiana 70112, United States; Recruiting
Lala Mathe Dunbar, Principal Investigator

GSK Investigational Site, Grand Blanc, Michigan 48439, United States; Recruiting
Kimball Silverton, Principal Investigator

GSK Investigational Site, Jackson, Mississippi 39216-4505, United States; Not yet recruiting
Rathel Nolan, Principal Investigator

GSK Investigational Site, Portland, Oregon 97210, United States; Recruiting
Phoebe Rich, Principal Investigator

GSK Investigational Site, Gresham, Oregon 97030, United States; Recruiting
Frank Calcagno, Principal Investigator

GSK Investigational Site, Corvallis, Oregon 97330, United States; Recruiting
Robin Lannan, Principal Investigator

GSK Investigational Site, Hazleton, Pennsylvania 18201, United States; Not yet recruiting
Stephen M Schleicher, Principal Investigator

GSK Investigational Site, Austin, Texas 78738, United States; Recruiting
Daniel V Freeland, Principal Investigator

GSK Investigational Site, Dallas, Texas 75204, United States; Not yet recruiting
Nicholaos C Bellos, Principal Investigator

GSK Investigational Site, Duncanville, Texas 75116, United States; Not yet recruiting
Bill Way, Principal Investigator

GSK Investigational Site, Fort Worth, Texas 76107, United States; Not yet recruiting
Barbara Atkinson, Principal Investigator

GSK Investigational Site, Fort Worth, Texas 76107, United States; Not yet recruiting
Clifton Cage, Principal Investigator

GSK Investigational Site, Houston, Texas 77030, United States; Not yet recruiting
Adelaide A Hebert, Principal Investigator

GSK Investigational Site, Dallas, Texas 75390-9113, United States; Not yet recruiting
Amit Pandya, Principal Investigator

GSK Investigational Site, Layton, Utah 84041, United States; Recruiting
Michael P Husseman, Principal Investigator

GSK Investigational Site, Seattle, Washington 98101, United States; Not yet recruiting
Bernard Goffe, Principal Investigator

Starting date: April 2009
Ending date: August 2010
Last updated: October 15, 2009