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

Skin Infections, Bacterial Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00684177
• Other study ID #: TOC110977
• Status: Completed
• Phase: Phase 3
• First received: May 22, 2008
• Last updated: August 23, 2012
• Start date: May 2008
• Est. completion date: October 2009

Study information

• Verified date: August 2012
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 508
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Months and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bacterial Infections
• Lacerations
• Secondarily-infected Abrasions
• Secondarily-infected Lacerations
• Secondarily-infected Sutured Wounds
• Secondarily-infected Traumatic Lesions
• Skin Diseases, Infectious
• Skin Infections, Bacterial

Intervention

Drug:
• Retapamulin Ointment, 1%
Provided as approximately 10 grams of an off-white smooth ointment in collapsible aluminum tubes with reverse taper puncture tip caps.
• Placebo ointment
Provided as approximately 10 grams of an off-white smooth ointment in collapsible aluminum tubes with reverse taper puncture tip caps.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Chivilocoy	Buenos Aires
Argentina	GSK Investigational Site	Loma Hermosa	Buenos Aires
Brazil	GSK Investigational Site	Curitiba	Paraná
Brazil	GSK Investigational Site	Curitiba/Paraná	Paraná
Brazil	GSK Investigational Site	Passo Fundo	Rio Grande Do Sul
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Lucknow
India	GSK Investigational Site	Pune
India	GSK Investigational Site	Vadodara
India	GSK Investigational Site	Wardha
South Africa	GSK Investigational Site	Belville
South Africa	GSK Investigational Site	Benoni
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Hatfield
South Africa	GSK Investigational Site	Lynnwood
South Africa	GSK Investigational Site	Midrand
South Africa	GSK Investigational Site	Newton
South Africa	GSK Investigational Site	Welkom
South Africa	GSK Investigational Site	Worcester
United States	GSK Investigational Site	Anaheim	California
United States	GSK Investigational Site	Arlington Heights	Illinois
United States	GSK Investigational Site	Bountiful	Utah
United States	GSK Investigational Site	Brooklyn	New York
United States	GSK Investigational Site	Brooklyn	New York
United States	GSK Investigational Site	Butte	Montana
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Deerfield Beach	Florida
United States	GSK Investigational Site	East Syracuse	New York
United States	GSK Investigational Site	Fresno	California
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Hollywood	Florida
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Irvine	California
United States	GSK Investigational Site	Johnson City	New York
United States	GSK Investigational Site	Kansas City	Kansas
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	New Orleans	Louisiana
United States	GSK Investigational Site	Norristown	Pennsylvania
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Panama City	Florida
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	Teaneck	New Jersey
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Uniontown	Pennsylvania
United States	GSK Investigational Site	Vero Beach	Florida
United States	GSK Investigational Site	Vienna	Virginia
United States	GSK Investigational Site	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  India,  South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Clinical Success and Failure at Follow-up (7-9 Days Post Therapy) for the Primary Efficacy Population	"Clinical Success" at follow-up was defined as "Resolution of clinically meaningful signs and symptoms of infection recorded at baseline including a pus/exudate Skin Infection Rating Scale (SIRS) score of "0". Clinical response at follow-up was classified as "Clinical Failure" for all other cases. The SIRS consists of seven items (pus/exudates, crusting, erythema/inflammation, tissue warmth, tissue edema, itching and pain). Each item has a score ranging from 0 to 6 (0=absent, 6=severe). The SIRS total score was calculated as the sum of the scores of all 7 SIRS items.	Days 12-14	No
Secondary	Number of Participants With Clinical Success and Failure at Follow-up (7-9 Days Post Therapy) for the Intent-to-Treat Bacteriology (ITTB) Subset of the Primary Efficacy Population	"Clinical Success" at follow-up was defined as "Resolution of clinically meaningful signs and symptoms of infection recorded at baseline including a pus/exudate Skin Infection Rating Scale (SIRS) score of "0". Clinical response at follow-up was classified as "Clinical Failure" for all other cases. The SIRS consists of seven items (pus/exudates, crusting, erythema/inflammation, tissue warmth, tissue edema, itching and pain). Each item has a score ranging from 0 to 6 (0=absent, 6=severe). The SIRS total score was calculated as the sum of the scores of all 7 SIRS items.	Days 12-14	No
Secondary	Number of Participants With Microbiological Success and Failure at Follow-up (7-9 Days Post Therapy)	The "by pathogen" microbiological outcome was determined by comparing the baseline culture results to those at follow-up. The "by subject" microbiological response was "Microbiological Success" if the microbiological outcomes for all baseline pathogens (bps) belong to "Eradication" (elimination of bps), "Presumed Eradication" (clinical outcome was success; no culture was obtained due to lack of culturable material), or "Colonization" (previously unidentified pathogen is identified at end of therapy in participant who is resolved/improved); otherwise, response was "Microbiological Failure".	Days 12-14	No
Secondary	Number of Participants With the Indicated Clinical Outcome at End of Therapy (2-4 Days Post Therapy)	Clinical outcome is determined by the investigator based on signs and symptoms (S/S) at the end of therapy evaluation. The 4 clincal outcome categories are: clinical success, resolution of clinically meaningful S/S of infection recorded at baseline (BL), including a pus/exudates score of 0; clinical improvement, improvement of S/S of infection recorded at BL to such an extent that no further antimicrobial therapy is necessary; clinical failure, insufficient improvement of deterioration of S/S of infection recorded at BL such that additional antibiotic therapy is required; unable to determine.	Days 7-9	No
Secondary	Number of Baseline Pathogens With the Indicated Microbiological Outcome at End of Therapy (2-4 Days Post Therapy)	The "by pathogen" microbiological outcome was determined by comparing the baseline culture results to those at follow-up. The results presented below pooled all baseline pathogens (bps). Eradication: elimination of bps. Presumed Eradication: clinical outcome was success; no culture was obtained due to lack of culturable material. Presumed Improvement: clinical outcome was improvement such that no culture was obtained due to lack of culturable material. Persistence: bps still present. Presumed persistence: clinical failure and no culture was obtained.	Days 7-9	No
Secondary	Number of Participants With Therapeutic Success and Failure at Follow-up (7-9 Days Post Therapy)	"Therapeutic Success (Succ)" was referred to as both "Clinical Succ" and "Microbiological (Micro) Succ" at Follow-up. "Clinical Succ" was the "Resolution of baseline signs/symptoms of infection with a pus score of "0." A participant was "Micro Succ" if the micro outcome for all baseline pathogens (bps) belonged to "Eradication" (elimination of bps), "Presumed Eradication" (clinical outcome is success; no culturable material), or "Colonization" (new pathogen is identified at end of therapy in participants who are resolved/improved). All other combinations were deemed "Therapeutic Failures."	Follow-up (Days 12-14)	No