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.

Study Overview

• Status: Completed
• Conditions: Skin Infections, Bacterial
• Intervention / Treatment: Drug: Retapamulin Ointment, 1%; Drug: Placebo ointment

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 508
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, CP1431FWO
    • GSK Investigational Site
  • Buenos Aires, Argentina, C1180AAX
    • GSK Investigational Site
  • Buenos Aires
    • Chivilocoy, Buenos Aires, Argentina, 6620
      • GSK Investigational Site
    • Loma Hermosa, Buenos Aires, Argentina, 1657
      • GSK Investigational Site
• Brazil
  • Paraná
    • Curitiba, Paraná, Brazil, 80240-280
      • GSK Investigational Site
    • Curitiba/Paraná, Paraná, Brazil, 80810-050
      • GSK Investigational Site
  • Rio Grande Do Sul
    • Passo Fundo, Rio Grande Do Sul, Brazil, 99010-080
      • GSK Investigational Site
• India
  • Bangalore, India, 560002
    • GSK Investigational Site
  • Lucknow, India, 226003
    • GSK Investigational Site
  • Pune, India
    • GSK Investigational Site
  • Vadodara, India, 390001
    • GSK Investigational Site
  • Wardha, India, 442102
    • GSK Investigational Site
• South Africa
  • Belville, South Africa, 7530
    • GSK Investigational Site
  • Benoni, South Africa, 1501
    • GSK Investigational Site
  • Cape Town, South Africa, 7572
    • GSK Investigational Site
  • Cape Town, South Africa
    • GSK Investigational Site
  • Hatfield, South Africa, 83
    • GSK Investigational Site
  • Lynnwood, South Africa, 81
    • GSK Investigational Site
  • Midrand, South Africa, 1
    • GSK Investigational Site
  • Newton, South Africa, 6045
    • GSK Investigational Site
  • Welkom, South Africa, 9460
    • GSK Investigational Site
  • Worcester, South Africa, 6850
    • GSK Investigational Site
• United States
  • Arizona
    • Tucson, Arizona, United States, 85705
      • GSK Investigational Site
  • California
    • Anaheim, California, United States, 92804
      • GSK Investigational Site
    • Fresno, California, United States, 93710
      • GSK Investigational Site
    • Irvine, California, United States, 90620
      • GSK Investigational Site
    • Los Angeles, California, United States, 90048
      • GSK Investigational Site
    • Sacramento, California, United States, 95825
      • GSK Investigational Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80904
      • GSK Investigational Site
  • Florida
    • Deerfield Beach, Florida, United States, 33441
      • GSK Investigational Site
    • Hollywood, Florida, United States, 33023
      • GSK Investigational Site
    • Miami, Florida, United States, 33144
      • GSK Investigational Site
    • Miami, Florida, United States, 33155
      • GSK Investigational Site
    • Orlando, Florida, United States, 32712
      • GSK Investigational Site
    • Panama City, Florida, United States, 32401
      • GSK Investigational Site
    • Tampa, Florida, United States, 33606
      • GSK Investigational Site
    • Vero Beach, Florida, United States, 32960
      • GSK Investigational Site
    • West Palm Beach, Florida, United States, 33401
      • GSK Investigational Site
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • GSK Investigational Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • GSK Investigational Site
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • GSK Investigational Site
  • Montana
    • Butte, Montana, United States, 59701
      • GSK Investigational Site
  • New Jersey
    • Teaneck, New Jersey, United States, 07666
      • GSK Investigational Site
  • New York
    • Brooklyn, New York, United States, 11229
      • GSK Investigational Site
    • Brooklyn, New York, United States, 11218
      • GSK Investigational Site
    • East Syracuse, New York, United States, 13057
      • GSK Investigational Site
    • Johnson City, New York, United States, 13790
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45246
      • GSK Investigational Site
  • Pennsylvania
    • Norristown, Pennsylvania, United States, 19401
      • GSK Investigational Site
    • Uniontown, Pennsylvania, United States, 15401
      • GSK Investigational Site
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • GSK Investigational Site
  • Texas
    • Houston, Texas, United States, 77036
      • GSK Investigational Site
  • Utah
    • Bountiful, Utah, United States, 84010
      • GSK Investigational Site
  • Virginia
    • Vienna, Virginia, United States, 22180
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Retapamulin Ointment, 1%	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.; Other Names: 1%; Retapamulin Ointment
PLACEBO_COMPARATOR: Placebo Ointment	Drug: Placebo ointment; Provided as approximately 10 grams of an off-white smooth ointment in collapsible aluminum tubes with reverse taper puncture tip caps.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: May 1, 2008
• Primary Completion (ACTUAL): October 1, 2009
• Study Completion (ACTUAL): October 1, 2009

Study Registration Dates

• First Submitted: May 22, 2008
• First Submitted That Met QC Criteria: May 22, 2008
• First Posted (ESTIMATE): May 26, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): November 23, 2016
• Last Update Submitted That Met QC Criteria: October 11, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: placebo; infection; retapamulin; secondarily-infected traumatic lesions
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Infections; Inflammation; Connective Tissue Diseases; Bacterial Infections and Mycoses; Suppuration; Cellulitis; Skin Diseases, Infectious; Bacterial Infections; Anti-Infective Agents; Anti-Bacterial Agents; Retapamulin
• Other Study ID Numbers: TOC110977

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Annotated Case Report Form
   Information identifier: TOC110977
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: TOC110977
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: TOC110977
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: TOC110977
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: TOC110977
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Informed Consent Form
   Information identifier: TOC110977
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Dataset Specification
   Information identifier: TOC110977
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register