E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10021531 |
E.1.2 | Term | Impetigo |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
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 |
The primary objective is to compare the efficacy of a twice daily topical application for 5 days (10 applications) of an ozenoxacin 1% cream versus placebo in patients with impetigo. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
- to evaluate the safety and tolerability of a twice daily topical application for 5 days (10 applications) of ozenoxacin 1% cream and retapamulin 1% ointment in patients with impetigo.
- to compare the efficacy of a twice daily topical application for 5 days (10 applications) of retapamulin 1% ointment versus placebo in patients with impetigo (to assess internal validity).
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients will be entered into this study only if they meet all of the following criteria:
1. Written informed consent from the patient, legally acceptable representative or parent and able to follow study procedures.
2. Male and female patients ≥2 years of age.
3. Clinical diagnosis of bullous or non bullous impetigo. The patient has a total affected area comprised between 1-100 cm2 with surrounding erythema not extending more than 2 cm from the edge of any affected area. In case of multiple affected areas the total area will be the sum of each affected area and will not exceed 100 cm2. Additionally for patients < 12 years the total area will not exceed a maximum of 2% of the body surface area.
4. Total Skin Infection Rating Scale (SIRS) score of at least 8, including pus/exudate score of at least 1
5. Females of childbearing potential must use a reliable method of contraception (i.e. barrier type devices [e.g. female condom, diaphragm, contraceptive sponge] only in combination with a spermicide; intra-uterine devices; oral, injectable, transdermal or implantable contraceptives only in combination with a barrier method). Females are not of childbearing potential if they are pre-menarchical, postmenopausal (i.e. amenorrhea for at least 1 year prior to screening), or surgically sterile (tubal ligation and/or hysterectomy).
|
|
E.4 | Principal exclusion criteria |
Patients that meet any of the following criteria must not be enrolled in the study:
1. Has an underlying skin disease, such as pre-existing eczematous dermatitis, with clinical evidence of secondary infection.
2. Has a bacterial infection, which in the opinion of the investigator, could not be appropriately treated by a topical antibiotic.
3. Has systemic signs and symptoms of infection (e.g. a fever; defined as an axillary temperature over 37.2 °C (99.0 °F)
4. Documented or suspected bacteraemia.
5. Treatment with the following anti-infective agents prior to study drug administration: oral antibiotic within 7 days; topical antibiotic (at the investigational area(s) or within 5 cm from the edge of the investigational area(s)), within 7 days; a long-acting injectable antibiotic within 30 days.
6. Has applied any topical therapeutic agent (including, but not limited to, glucocorticoid steroids) directly to the impetigo lesions within 24 hours before entry into the study.
7. Has applied any topical (at the investigational area(s) or within 5 cm from the edge of the investigational area(s)) treatment with antiseptics (e.g. alcohol, chlorhexidine, hydrogen peroxide or iodine) or other treatment that in the investigator’s opinion could confound the evaluation of the treatment effect on the investigational area(s) within 8 hours before study start or planned treatment during the study.
8. Has taken any systemic or topical (at the investigational area(s) or within 5 cm from the edge of the investigational area(s)) treatment with analgesics, anti-inflammatory or antihistaminic within 8 hours before entry into the study.
9. Daily dose of >15 mg of systemic prednisone or equivalent for >10 days within the period starting 14 days prior to study drug administration or anticipated through the study period.
10. Known human immunodeficiency virus (HIV) infection, or evidence of clinically significant immunosuppression.
11. Current medical history of uncontrolled diabetes.
12. Is pregnant or lactating.
13. Known or suspected hypersensitivity to quinolones or any of the excipients in the cream of the investigational product.
14. Known or suspected hypersensitivity to retapamulin or any of the excipients in the ointment of the investigational product.
15. Underlying condition and/or disease that, according to the judgment of the Investigator, would be likely to interfere with completion of the course of study drug therapy or follow-up.
16. Have received treatment with any other investigational drug in the last 30 days before study entry.
17. Have previously been enrolled in this study.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Clinical response (clinical success or clinical failure) at end of therapy (Visit 3, Day 6-7) in the intent-to-treat clinical (ITTC) population. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary Efficacy Endpoints
• Clinical response (clinical success or clinical failure) at end of therapy (Visit 3, Day 6-7) in the per protocol clinical (PPC), per protocol bacteriological (PPB), and intent-to-treat bacteriological (ITTB) populations.
• Clinical response (clinical improvement, no clinical improvement) at Visit 2 (Day 3-4) in the ITTC, PPC, ITTB, and PPB populations.
• Clinical response (clinical success, clinical unchange, clinical relapse) at Visit 4 (Day 10-13) in the ITTC, PPC, ITTB, and PPB population.
• The difference from baseline (Visit 1, Day 1) in Skin Infection Rating Scale (SIRS) scores at Visit 2 (Day 3-4), Visit 3 (Day 6-7) and Visit 4 (Day 10-13) in the ITTC, PPC, ITTB, and PPB populations.
• Size of the affected area at Visit 2 (Day 3-4), Visit 3 (Day 6-7) and Visit 4 (Day 10-13) as a ratio of baseline (Visit 1) in the ITTC, PPC, ITTB, and PPB populations.
• Microbiological response (microbiological success or microbiological failure) at Visit 2 (Day 3-4) and Visit 3 (Day 6-7) in the ITTB, and PPB population.
• Microbiological response (microbiological recurrence or microbiological reinfection) at Visit 4 (Day 10-13) in the ITTB, and PPB population.
• Clinical and Microbiological response at Visit 2 (Day 3-4), Visit 3 (Day 6-7) and Visit 4 (Day 10-13) by microbiological susceptibility profile of pathogens identified at Visit 1 to methicilin, ciprofloxacin, retapamulin, mupirocin and fusidic acid and the presence of pvl gene in the ITTB and PPB populations.
• Therapeutic response (combined clinical and microbiological response-success or failure) at visit 3 in the ITTB and PPB populations.
• Time to clinical response: Clinical improvement/cure/post therapy cure will be summarised through time for each patient population (ITTC, PPC, ITTB and PPB) through Tables summarising the Visit (Days) at which improvement/cure/post therapy cure was first recorded (and was then sustained) for each patient.
• Time to bacterial eradication: Bacterial clearance will be summarised through time for each patient population (ITTB and PPB) through Tables summarising the Visit (Days) at which eradication or presumed eradication was first recorded (and was then sustained) for each patient.
Secondary Safety Endpoints
Evaluation of safety is based on the following parameters:
• AEs
• Clinical laboratory parameters (haematology, clinical chemistry, urinalysis).
• Vital signs (axillary temperature, respiratory rate, pulse rate, Blood Pressure).
• Physical examination.
• Treatment compliance.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary Efficacy Endpoints
Please refer to previous section
Secondary Safety Endpoints
At Visit 1 (Day 1), Visit 2 (Day 3-4), Visit 3 (Day 6-7) and Visit 4 (Day 10-13) |
|
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 | No |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Investigator blinded for the retapamulin comparison |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 14 |
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 | No |
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 |
Germany |
India |
Romania |
South Africa |
Ukraine |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
The end of the trial is defined as the date on which the last patient completes his/her last study visit (Visit 4, Day 10-13) |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |