E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
secondarily-infected traumatic lesions (SITL; excluding abscesses) or impetigo due
to methicillin-resistant Staphylococcus aureus (MRSA
|
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
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 of this study is to evaluate the clinical and bacteriological efficacy
of topical retapamulin ointment, 1%, versus oral linezolid, in the treatment of subjects
with secondarily-infected traumatic lesions (SITL; excluding abscesses) or impetigo due
to methicillin-resistant Staphylococcus aureus (MRSA). |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the safety of topical retapamulin ointment, 1%, versus linezolid, in the
treatment of subjects with SITL (excluding abscesses) or impetigo due to MRSA.
To evaluate the efficacy and safety of topical retapamulin ointment, 1%, versus linezolid,
in the treatment of subjects with SITL (excluding abscesses) or impetigo, without regard
to pathogen. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The subject is aged 2 months or older.
2. The subject has a secondarily infected traumatic lesion (SITL) or impetigo (bullous
or non-bullous).
3. The subject has had a negative urine pregnancy test prior to enrolment (if of
childbearing potential).
4. The subject has a Total Skin Infection Rating Scale (SIRS) Score of at least 8, which
must include a pus/exudate score of at least 3 (see Appendix 1).
5. The subject and/or parent/legal guardian is willing and able to comply with the study
protocol.
6. The subject or parent/legal guardian, as applicable, has given written informed, dated
consent; and the subject has given written assent, if applicable, to participate in the
study.
|
|
E.4 | Principal exclusion criteria |
1. The subject has demonstrated a previous hypersensitivity reaction to pleuromutilins
or any component of the retapamulin ointment, or to oxazolidinones.
2. The subject has phenylketonuria (PKU) or known hypersensitivity to aspartame.
3. The subject has a secondarily infected animal/human bite, or a puncture wound.
4. The subject has an abscess; defined as a localized collection of pus caused by
suppuration buried in tissues.
5. The subject has a chronic ulcerative lesion that is likely to be polymicrobial and
unlikely to have Staphylococcus aureus as the causative agent.
6. The subject has an underlying skin disease, such as pre-existing eczematous
dermatitis, with clinical evidence of secondary infection.
7. The subject has systemic signs and symptoms of infection (e.g., a fever; defined as a
rectal temperature greater than 101° F or 38.3° C).
8. The subject has a bacterial skin infection which, due to extent, depth or severity, in
the opinion of the investigator, cannot be appropriately treated by a topical antibiotic
(e.g., extensive cellulitis, furunculosis).
9. The subject requires surgical intervention including, but not limited to, incision and
drainage, for treatment of the infection prior to enrollment in the study, or is likely to
require such intervention during the course of the study. This includes subjects who
have infected surgical wounds from an amputation.
10. The subject has received a systemic antibacterial or steroid, or has applied any
topical therapeutic agent (including glucocorticoid steroids, antibacterials and
antifungals) directly to the wound, within 24 hours of entry into the study.
11. The subject is currently receiving adrenergic agents (e.g., pseudoephedrine).
12. The subject is currently receiving serotonergic agents (i.e., antidepressants).
13. The subject has a clinical history of pseudomembranous colitis.
14. The subject has known, pre-existing myelosuppression, or a history of
myelosuppression with prior linezolid use, or is currently receiving a medication that
produces bone marrow suppression.
15. The subject has a history of seizures.
16. The subject has a history of severe renal failure and is undergoing dialysis.
17. The subject has a serious underlying disease that could be imminently lifethreatening.
18. The subject is pregnant, breast feeding or planning a pregnancy during the study, or
of childbearing potential or less than one year post-menopausal and not using an
accepted method of contraception (i.e., surgical sterilization, intra-uterine
contraceptive device, oral contraception plus barrier contraception, other hormone
delivery systems plus barrier contraception, diaphragm or condom in combination
with contraceptive cream, jelly or foam).
19. The subject has used an investigational drug within 30 days prior to entering the
study.
20. The subject has been previously enrolled in this study
21. The subject has fructose intolerance, glucose-galactose malabsorption, or sucraseisomaltase
insufficiency. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the clinical response at follow-up (7-9 days post-therapy; Day
12-14 for retapamulin and Day 17-19 for linezolid) in subjects with MRSA as the
baseline pathogen. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
(7 to 9 days post-therapy; ie. Day 12 to 14 for retapamulin and Day 17 to 19 for linezolid) |
|
E.5.2 | Secondary end point(s) |
• Microbiological response at follow-up in subjects with MRSA as the baseline
pathogen
• Clinical response at follow-up in all subjects
• Microbiological response at follow-up in all subjects with a baseline pathogen
• Clinical outcome at end of therapy (2-4 days post-therapy; Day 7-9 for retapamulin
and Day 12-14 for linezolid) in subjects with MRSA as the baseline pathogen
• Microbiological outcome at end of therapy in subjects with MRSA as the baseline
pathogen
• Clinical outcome at end of therapy in all subjects
• Microbiological outcome at end of therapy in all subjects with a baseline pathogen
• Therapeutic response (combined clinical and microbiological response) at follow-up |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
end of therapy (2 to 4 days post-therapy; ie. Day 7 to 9 for retapamulin and Day 12 to14 for linezolid) or at follow up (7 to 9 days post-therapy ie. Day 12 to 14 for retapamulin and Day 17 to 19 for linezolid) |
|
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
|
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
|
Last subject last visit – 27-Sep-2010 |
|
E.8.9 Initial estimate of the duration of the trial |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 19 |