Retapamulin Versus Placebo in Secondarily-Infected Traumatic Lesions (SITL)

A Randomized, Double-Blind, Multicenter, Placebo-controlled, Phase III Superiority Study to Assess the Safety and Efficacy of Topical Retapamulin Ointment, 1%, Versus Placebo Ointment Applied Twice Daily for 5 Days in the Treatment of Adult and Pediatric Subjects With SITL

The purpose of Study TOC110977 is to demonstrate clinical superiority of Retapamulin ointment, 1%, over placebo in patients with secondarily-infected traumatic lesions, which includes secondarily-infected lacerations, abrasions and sutured wounds. Subjects 2 months of age and older will be treated with topical retapamulin or placebo ointment twice daily for 5 days. The primary endpoint of this study is the clinical response at follow-up (Day 12-14; 7-9 days after the end of therapy) in the intent-to-treat clinical population.

This is a prospective, multicenter, double-blind, placebo-controlled parallel group study in subjects aged 2 months and older with SITL, including secondarily-infected lacerations, sutured wounds or abrasions. 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.

There are four study visits occurring over a 12-14 day period. At the Baseline visit (Visit 1, Day 1), subjects will be randomized to receive retapamulin or placebo ointment in a 2:1 (retapamulin:placebo) ratio. The 2:1 randomization is included to minimize the number of subjects exposed to treatment with placebo. Both active treatment and placebo will be dosed topically twice daily (BID) for 5 days. All subjects will receive a telephone call from the investigator or appropriate designee appointed by the investigator on Day 2. The subject will be interviewed to determine if there is any evidence of worsening infection. Subjects who are thought to be worsening will be instructed to come in to the clinic for an assessment. Subjects will be monitored and clinically evaluated at the On-therapy (Days 3-4), End of Therapy (Days 7-9), and Follow-up (Days 12-14) visits.

Randomization will be center-based and 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:

• subject is aged 2 months or older
• subject has secondarily-infected traumatic lesion (laceration, sutured wound or abrasion)
• negative urine pregnancy test
• subject has total skin infection rating scale score of at least 8, including pus/exudate score of at least 3
• subject and/or parent/legal guardian is willing and able to comply with protocol
• subject or parent/legal guardian has given written informed consent or assent as applicable

Exclusion criteria:

• previous hypersensitivity to pleuromutilin
• secondarily-infected animal/human bite or puncture wound
• subject has an abscess
• chronic ulcerative lesion
• underlying skin disease
• systemic signs and symptoms of infection
• infection not appropriately treated with topical antibiotic
• infection requires surgical intervention prior to or during study
• subject received systemic antibacterial or steroid, or topical therapeutic agent within 24 hours of entry into study
• serious underlying disease
• subject pregnant, breast feeding or planning a pregnancy, or unacceptable method of contraception
• other investigational drug within 30 days of study entry
• subject previously enrolled in this study