Skin Infections, Bacterial
Conditions
Keywords
SID, impetigo, pharmacokinetics, Retapamulin ointment, 1%, Skin abnormalities, Dermatoses, pediatric, infection, SITL
Brief summary
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).
Interventions
1% Ointment
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Months to 24 Months
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Measurable Plasma Concentrations, by Age Group | Days 3 to 4; 4 to 8 hours post-dose of the first dose of the day | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Success at Follow-up, by Type of Skin Infection and by Age | Follow-up, Days 12 to 16 | 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. |
| Bacteriological Success Rate at Follow-up, by Baseline Pathogen | Follow-up, Days 12 to 16 | 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. |
| Number of Participants by Age With Therapeutic Response of Success | Follow-up, Days 12 to 16 | 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. |
Countries
Argentina, Chile, Costa Rica, Germany, Mexico, Netherlands, South Africa, Taiwan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Retapamulin Ointment, 1% Retapamulin ointment, 1%, administered twice daily for 5 consecutive days | 86 |
| Total | 86 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 3 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Participant enrolled, but never treated | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Retapamulin Ointment, 1% |
|---|---|
| Age, Continuous | 10.6 months STANDARD_DEVIATION 6.89 |
| Gender Female | 32 Participants |
| Gender Male | 54 Participants |
| Race/Ethnicity, Customized African American/African Heritage | 46 participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 participants |
| Race/Ethnicity, Customized Central/South Asian | 1 participants |
| Race/Ethnicity, Customized East Asian | 1 participants |
| Race/Ethnicity, Customized Missing | 1 participants |
| Race/Ethnicity, Customized White/Caucasian | 36 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 11 / — |
| serious Total, serious adverse events | 1 / — |
Outcome results
Primary
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.
Time frame: Days 3 to 4; 4 to 8 hours post-dose of the first dose of the day
Population: Pharmacokinetic (PK) Population: all participants who received at least one dose of study medication and who had PK samples taken. Seven participants did not have PK samples collected.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retapamulin Ointment, 1% | Number of Participants With Measurable Plasma Concentrations, by Age Group | All ages | 36 participants |
| Retapamulin Ointment, 1% | Number of Participants With Measurable Plasma Concentrations, by Age Group | ≥2 months to ≤6 months | 17 participants |
| Retapamulin Ointment, 1% | Number of Participants With Measurable Plasma Concentrations, by Age Group | >6 months to ≤12 months | 10 participants |
| Retapamulin Ointment, 1% | Number of Participants With Measurable Plasma Concentrations, by Age Group | >12 months to ≤24 months | 9 participants |
Secondary
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.
Time frame: Follow-up, Days 12 to 16
Population: ITTB (Intent-to-Treat Bacteriological) Population: participants who had at least one dose of study medication and a clinical diagnosis of infection plus a pathogen isolated at Baseline. Participants with more than one pathogen may be represented in the table more than once.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retapamulin Ointment, 1% | Bacteriological Success Rate at Follow-up, by Baseline Pathogen | All pathogens, n=93 | 79 number of pathogens eradicated |
| Retapamulin Ointment, 1% | Bacteriological Success Rate at Follow-up, by Baseline Pathogen | Staphylococcus aureus (SA), n=44 | 40 number of pathogens eradicated |
| Retapamulin Ointment, 1% | Bacteriological Success Rate at Follow-up, by Baseline Pathogen | Methicillin-resistant SA, n=3 | 3 number of pathogens eradicated |
| Retapamulin Ointment, 1% | Bacteriological Success Rate at Follow-up, by Baseline Pathogen | Methicillin-susceptible SA, n=41 | 37 number of pathogens eradicated |
| Retapamulin Ointment, 1% | Bacteriological Success Rate at Follow-up, by Baseline Pathogen | Mupirocin-susceptible SA, n=44 | 40 number of pathogens eradicated |
| Retapamulin Ointment, 1% | Bacteriological Success Rate at Follow-up, by Baseline Pathogen | Fuscidic acid-resistant SA, n=2 | 2 number of pathogens eradicated |
| Retapamulin Ointment, 1% | Bacteriological Success Rate at Follow-up, by Baseline Pathogen | Fuscidic acid-susceptible SA, n=42 | 38 number of pathogens eradicated |
| Retapamulin Ointment, 1% | Bacteriological Success Rate at Follow-up, by Baseline Pathogen | Streptococcus pyogenes, n=9 | 9 number of pathogens eradicated |
| Retapamulin Ointment, 1% | Bacteriological Success Rate at Follow-up, by Baseline Pathogen | Other Gram (+) pathogens, n=11 | 9 number of pathogens eradicated |
| Retapamulin Ointment, 1% | Bacteriological Success Rate at Follow-up, by Baseline Pathogen | Gram (-) pathogens, n=29 | 21 number of pathogens eradicated |
Secondary
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.
Time frame: Follow-up, Days 12 to 16
Population: ITTB and ITTC Populations. The number analyzed is the number of participants who were clinical successes both in the ITTC Population and the ITTB Population; the number of participants who were therapeutic successes out of the total number in each respective category is shown.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retapamulin Ointment, 1% | Number of Participants by Age With Therapeutic Response of Success | >12 months to <=24 months, n=20 | 19 participants |
| Retapamulin Ointment, 1% | Number of Participants by Age With Therapeutic Response of Success | All ages | 51 participants |
| Retapamulin Ointment, 1% | Number of Participants by Age With Therapeutic Response of Success | >2 months to <=6 months, n=21 | 15 participants |
| Retapamulin Ointment, 1% | Number of Participants by Age With Therapeutic Response of Success | >6 months to <=12 months, n=20 | 17 participants |
Secondary
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.
Time frame: Follow-up, Days 12 to 16
Population: Intent-to-Treat Clinical (ITTC) Population: all participants who received at least one dose of study medication; the number of participants who were clinical successes out of the total number in each respective category is shown
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Retapamulin Ointment, 1% | Number of Participants With Clinical Success at Follow-up, by Type of Skin Infection and by Age | Impetigo, ≥2 months to ≤6 months, n=11 | 10 participants |
| Retapamulin Ointment, 1% | Number of Participants With Clinical Success at Follow-up, by Type of Skin Infection and by Age | Impetigo, >6 months to ≤12 months, n=18 | 17 participants |
| Retapamulin Ointment, 1% | Number of Participants With Clinical Success at Follow-up, by Type of Skin Infection and by Age | Impetigo, >12 months to ≤24 months, n=18 | 17 participants |
| Retapamulin Ointment, 1% | Number of Participants With Clinical Success at Follow-up, by Type of Skin Infection and by Age | SID, ≥2 months to ≤6 months, n=17 | 11 participants |
| Retapamulin Ointment, 1% | Number of Participants With Clinical Success at Follow-up, by Type of Skin Infection and by Age | SID, >6 months to ≤12 months, n=9 | 7 participants |
| Retapamulin Ointment, 1% | Number of Participants With Clinical Success at Follow-up, by Type of Skin Infection and by Age | SID, >12 months to ≤24 months, n=4 | 4 participants |
| Retapamulin Ointment, 1% | Number of Participants With Clinical Success at Follow-up, by Type of Skin Infection and by Age | SITL, ≥2 months to ≤6 months, n=1 | 1 participants |
| Retapamulin Ointment, 1% | Number of Participants With Clinical Success at Follow-up, by Type of Skin Infection and by Age | SITL, >6 months to ≤12 months, n=2 | 2 participants |
| Retapamulin Ointment, 1% | Number of Participants With Clinical Success at Follow-up, by Type of Skin Infection and by Age | SITL, >12 months to ≤24 months, n=6 | 6 participants |