Pharmacokinetics of Retapamulin in Pediatric Subjects With Uncomplicated Skin Infections.

Study Overview
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Brief Summary
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A study to evaluate the pharmacokinetics of Retapamulin Ointment, 1%, in pediatric subjects (2-24 months) with secondarily-infected traumatic lesions, secondarily-infected dermatoses, or impetigo (bullous and non-bullous).

Official Title
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An Open-Label, Non-Comparative Study to Assess the Pharmacokinetics, Safety and Efficacy of Topical Retapamulin (SB-275833) Ointment, 1%, Twice Daily for Five Days in the Treatment of Uncomplicated Skin and Skin Structure Infections in Pediatric Subjects Aged 2 to 24 Months

Conditions
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Skin Infections, Bacterial

Intervention / Treatment
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* Drug: Retapamulin Ointment, 1%


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subject Age: The subject is ≥2 months to ≤24 months of age at study entry Subject Diagnosis: The subject has a diagnosis of secondarily-infected traumatic lesion (SITL), secondarily-infected dermatoses (SID), or primary impetigo (bullous or non-bullous) that is suitable for treatment with topical antibacterial therapy: The subject has a small laceration, sutured wound or abrasion, which has a secondary bacterial infection. The infected portion of the laceration or sutured wound should not exceed 10cm in length with surrounding erythema not extending more than 2cm from the edge of the wound. Abrasions should not exceed 2% of the total body surface area with surrounding erythema not extending more than 2cm from the edge of the abrasion. The subject has a diagnosis of inflammatory skin disease (i.e., dermatosis), such as atopic dermatitis or contact dermatitis, which has a secondary bacterial infection. The infected portion of the lesion(s) should not exceed 2% of the total body surface area. Impetigo: The subject has a lesion or group of £10 discrete localized lesions on otherwise healthy skin, characterized by red spots or blisters without crusts which later progress to lesions which ooze and form yellow or honey-colored crusts surrounded by an erythematous margin. Subject SIRS Score: The subject has a total SIRS score of at least 8 (Appendix 1 Skin Infection Rating Scale) Protocol Compliance: The parent/legal guardian is willing to comply with the protocol Informed Consent: The parent/legal guardian has given written informed, dated consent for the subject to participate in the study French Subjects: In France, a subject will be eligible for inclusion in this study if either affiliated to or a beneficiary of a social security category Exclusion criteria: The subject has demonstrated a previous hypersensitivity reaction to pleuromutilin or any component of the ointment (refer to the Investigator Brochure for composition of Retapamulin ointment, 1%) The subject was considered to be premature at birth (<37 weeks gestation) The subject has a secondarily-infected animal/human bite, or a puncture wound The subject has an abscess The subject has a chronic ulcerative lesion that is unlikely to have Staphylococcus aureus or Streptococcus pyogenes as the causative agent The subject has systemic signs and symptoms of infection (such as fever; defined as a temperature equivalent to a rectal temperature greater than 101°F or 38.3°C) The subject has a bacterial skin infection which, due to area, depth or severity, in the opinion of the investigator, cannot be appropriately treated by a topical antibiotic The subject has more than one type of infected lesion as defined in the protocol The subject requires surgical intervention for treatment of the infection prior to enrollment in the study, or is likely to require such intervention during the course of the study The subject has applied any topical therapeutic agent (including glucocorticoid steroids, antibacterials or antifungals) directly to the infected wound/lesion, within 24 hours prior to study entry The subject has received one or more days of treatment with a systemic antibacterial within 72 hours of study entry The subject is receiving systemic corticosteroids at a dose of >0.125mg/kg per day of prednisone (or the equivalent) The subject has a known, pre-existing, serious underlying disease that could be imminently life-threatening The subject has participated in any study using an investigational drug during the previous 30 days prior to entering the study The subject has been previously enrolled in this study or in any other study involving Retapamulin

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>Single Arm Retapamulin 1% Ointment | Drug: Retapamulin Ointment, 1%<br>* 1% Ointment<br>* Other names: 1%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Measurable Plasma Concentrations, by Age Group | Pharmacokinetic (PK) samples were collected randomly in the window of 4 to 8 hours post-dose (except one at 3 hours and one at 11 hours post-dose) after the first daily dose of treatment on Day 3 or Day 4. The lower limit of quantification (LLQ) for retapamulin was 0.5 ng/mL. | Days 3 to 4; 4 to 8 hours post-dose of the first dose of the day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Clinical Success at Follow-up, by Type of Skin Infection and by Age | SID = Secondarily Infected Dermatoses; SITL = Secondarily Infected Traumatic Lesions. Clinical Success is the number of participants with resolution of signs/symptoms of infection or improvement such that no additional antibiotic therapy was needed. | Follow-up, Days 12 to 16 | 
| Bacteriological Success Rate at Follow-up, by Baseline Pathogen | Bacteriological success is defined as: (1) Bacteriological Eradication, elimination of the baseline pathogen via culture results; (2) Presumed Bacteriological Eradication, clinical success plus no culturable material from the wound; or (3) Colonization, new pathogen identified at Follow-up in a non-symptomatic participant who does not require additional antibiotic therapy. The number of pathogens eradicated out of the number isolated (shown as n in the category title) for each respective category is shown. | Follow-up, Days 12 to 16 | 
| Number of Participants by Age With Therapeutic Response of Success | Therapeutic response is a measure of the overall efficacy response; a response of therapeutic success was based on both clinical success and bacteriological success in a given participant. | Follow-up, Days 12 to 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SID, impetigo, pharmacokinetics, Retapamulin ointment, 1%, Skin abnormalities, Dermatoses, pediatric, infection, SITL