E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Uncomplicated skin and skin structure infections |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To characterize the systemic exposure, by using pharmacokinetic (PK) sampling at four to eight hours post-dose, of Retapamulin Ointment, 1%, when applied topically, twice daily for five days, in the treatment of pediatric subjects aged ≥2 to ≤6 months, >6 to ≤12 months, and >12 to ≤24 months with uncomplicated skin and skin structure infections, including secondarily-infected traumatic lesions (SITL), secondarily-infected dermatoses (SID) and impetigo. |
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E.2.2 | Secondary objectives of the trial |
• To summarize the safety and tolerability of Retapamulin Ointment, 1% in the treatment of pediatric subjects aged ≥2 to ≤6 months, >6 to ≤12 months, and >12 to ≤24 months with uncomplicated skin and skin structure infections, including secondarily-infected traumatic lesions (SITL), secondarily-infected dermatoses (SID) and impetigo • To summarize the clinical and bacteriological efficacy of Retapamulin Ointment, 1%, in the treatment of pediatric subjects aged ≥2 to ≤6 months, >6 to ≤12 months, and >12 to ≤24 months with uncomplicated skin and skin structure infections, including secondarily-infected traumatic lesions (SITL), secondarily-infected dermatoses (SID) and impetigo
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject Age: The subject is ≥2 months to ≤24 months of age at study entry. 2. 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:
SITL: 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.
SID: 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.
3. Subject SIRS Score: The subject has a total SIRS score of at least 8 (Appendix 1 Skin Infection Rating Scale) 4. Protocol Compliance: The parent/legal guardian is willing to comply with the protocol. 5. Informed Consent: The parent/legal guardian has given written informed, dated consent for the subject to participate in the study.
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E.4 | Principal exclusion criteria |
1. Previous Hypersensitivity: 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%). 2. Prematurity: The subject was considered to be premature at birth (<37 weeks gestation). 3. Bite or puncture: The subject has a secondarily-infected animal/human bite, or a puncture wound. 4. Abscess: The subject has an abscess. 5. Unlikely to have S aureus or S pyogenes: The subject has a chronic ulcerative lesion that is unlikely to have Staphylococcus aureus or Streptococcus pyogenes as the causative agent. 6. Systemic Infection: 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). 7. Inappropriate for Topical Treatment: 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. 8. Infected Lesion Type: The subject has more than one type of infected lesion as defined in the protocol. 9. Surgical Intervention: 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. 10. Other Topicals: 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. 11. Systemic Antibacterials: The subject has received one or more days of treatment with a systemic antibacterial within 72 hours of study entry. 12. Systemic Corticosteriods: The subject is receiving systemic corticosteroids at a dose of >0.125mg/kg per day of prednisone (or the equivalent). 13. Serious Underlying Disease: The subject has a known, pre-existing, serious underlying disease that could be imminently life-threatening. 14. Other Investigational Drug: The subject has participated in any study using an investigational drug during the previous 30 days prior to entering the study. 15. Other Retapamulin Studies: The subject has been previously enrolled in this study or in any other study involving Retapamulin.
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E.5 End points |
E.5.1 | Primary end point(s) |
PK endpoint: Plasma concentrations of retapamulin at anytime during the window of 4 to 8 hours post-dose of the first dose on Visit 2 (day 3 or day 4) will be descriptively summarized by this pre-specified time window and by age groups (≥2 to ≤6 months, >6 to ≤12 months, and >12 to ≤24 months), if data permit.
Safety endpoint: Collection of safety data (including incidence of AEs and abnormal lab values).
Efficacy endpoints • Clinical response at Follow-up (Day 12-16) • Bacteriological response at Follow-up (Day 12-16) • Therapeutic response (combined clinical and bacteriological responses) at follow-up (Day 12-16)
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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When all data is received from sites and database is locked. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |