E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Complicated skin and skin structure infection (cSSSI) with or without methicillin-resistant Staphylococcus aureus (MRSA) |
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E.1.1.1 | Medical condition in easily understood language |
Complicated skin and skin structure infection (cSSSI) with or without methicillin-resistant Staphylococcus aureus (MRSA) |
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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 | 10040872 |
E.1.2 | Term | Skin infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066412 |
E.1.2 | Term | Staphylococcal aureus skin infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 | 10066409 |
E.1.2 | Term | Staphylococcal skin infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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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 relative safety and efficacy of tigecycline versus comparator (clindamycin or vancomycin) in the treatment of pediatric subjects (ages 8 to 17 years) with cSSSI including those caused by MRSA. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the microbiologic efficacy of tigecycline in the pediatric population. 2. To evaluate the PK/PD profile of tigecycline in pediatric subjects with cSSSI. 3. To obtain in vitro susceptibility data on tigecycline for a range of bacterial pathogens isolated from cSSSI. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subjects aged 8 to 17 years old. Children with bone maturation of less than 8 years old should be enrolled with caution due to potential risk of tooth discoloration. 2. All female and male subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control for the duration of the study and for 1 month after the last dose of any test article (a subject is biologically capable of having children even if he or she is using contraceptives or if his or her sexual partner is sterile or using contraceptives). 3. Presence of a cSSSI requiring hospitalization and administration of IV antibiotic therapy with anticipated length of IV antibiotic therapy greater than or equal to 5 days. 4. Have a cSSSI requiring significant surgical intervention or involving deeper soft tissue. This would include clinical entities such as one of the following (note that the following are examples): - infected wound; - infected decubitus ulcers (eg, perianal area); - burns (<20% body surface area, non-full thickness); - major abscess (not treatable through surgery alone); - deep or extensive cellulitis (eg, ≥10 cm where anatomically applicable and/or serious facial localization); - infected human or animal bites. Note: subjects with peripheral IV catheter site infections with documented purulent drainage will not be eligible for inclusion. 5. Have at least 3 of the following signs and symptoms: - drainage and/or discharge; - erythema; - swelling and/or induration and/or fluctuance; - localized warmth; - pain and/or tenderness to palpation. 6. Presence of at least 1 of the following systemic signs of infection: - fever (within the 24 hours before randomization) defined as a core temperature >38.5 C or <36 C (other methods are accepted); - white blood cell (WBC) >13.5 x 109/L (13,500/mm3 for age 8 to 12), >11 x 109/L (11,000/mm3 for age 13 to 17), <4.5 x 109/L (4,500/mm3) or >10% immature neutrophils (bands); - positive blood culture; - any 2 of the following: systolic blood pressure <105 mm Hg (age 8 to 12) or <117 mm Hg (age 13 to 17), tachycardia >130 beats/min (age 8 to 12) or >110 beats/min (age 13 to 17), or respiratory rate >18 breaths/min (age 8 to 12) or >14 breaths/min (age 13 to 17). |
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E.4 | Principal exclusion criteria |
1. Subjects with any concomitant illness/condition or taking any concomitant medication that, in the investigator’s judgment, will substantially increase the risk associated with the subject’s participation in and/ or completion of the study, or could preclude the evaluation of the subject’s response (eg, life expectancy <30 days). 2. Pregnant or breastfeeding female. 3. Participated in any investigational studies on drugs or devices within 4 weeks before administration of the first dose of test article. 4. Contraindication or hypersensitivity to any of the test articles that the subject may receive, including tetracycline (eg, anaphylaxis). 5. Presence of necrotizing fascitiis, gas gangrene, or known skeletal infection. 6. Received more than 24 hours of potentially effective systemic antibiotic before the first dose of test article to treat the current cSSSI infection, unless subject has been declared a clinical failure (no clinical improvement after 48 hours of treatment) or the causative organism(s) has been shown to be resistant to prior antibiotics. Note: Subjects may not have failed therapy with any antibiotic where cross resistance would be expected with an antibiotic used in this study. 7. Known or suspected infection due to a pathogenic organism known to be resistant to tigecycline or both clindamycin and vancomycin (eg, before T.A. administration). 8. Subjects with any of the following conditions: - cystic fibrosis; - endocarditis; - infected device that will not be removed; - active tuberculosis; - congenital immunodeficiency; - meningitis; - severe sepsis; - refractory shock (eg, in which hemodynamic parameters cannot be maintained despite adequate volume replacement); - confirmed malignancy with subject receiving active course of chemotherapeutic agents; - known or suspected infection with human immunodeficiency virus (HIV) (eg, positive HIV antibody); - known or suspected concomitant infection requiring systemic treatment. 9. Subjects receiving immunosuppressive therapy that, in the opinion of the investigator, would decrease the subject’s ability to eradicate the infection, including use of high-dose corticosteroids. 10. Concurrent hemodialysis, hemofiltration, peritoneal dialysis, or plasmapheresis. 11. Presence of any of the following laboratory findings: - Neutropenia (absolute neutrophil count <1 X 109/L [<1000/mm3]); - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5 x upper limit of normal (ULN); - Bilirubin >3 x ULN. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint will be the clinical response rate at the TOC visit for 2 co-primary populations: the CE population and the c-mITT population. The clinical response will be determined by the investigator at the TOC assessment, and one of the following outcomes will be assigned: cure, failure, or indeterminate. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Clinical response at the TOC visit for 2 co-primary populations: the clinically evaluable (CE) and the clinical modified intent-to-treat (c-mITT) populations. |
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E.5.2 | Secondary end point(s) |
Clinical response at IV last day of therapy (LDOT) and FUP visit, - microbiologic responses by subject and by pathogen at TOC and FUP visit. Microbiologic responses by subject and by pathogen at IV LDOT, TOC and FUP, cure rate by baseline respnose rate by baseline pathogen and MIC value, response rate for polymicrobial/monomicrobial infections, and, susceptibility evaluations. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Clinical response at IV last day of therapy (LDOT) and FUP visit, - microbiologic responses by subject and by pathogen at TOC and FUP visit. Microbiologic responses by subject and by pathogen at IV LDOT, TOC and FUP, cure rate by baseline response rate by baseline pathogen and MIC value, response rate for polymicrobial/monomicrobial infections, and susceptibility evaluations. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 |
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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 |
Argentina |
Australia |
Brazil |
Canada |
Chile |
China |
Colombia |
Croatia |
Guatemala |
Korea, Republic of |
Mexico |
Panama |
Peru |
Russian Federation |
Serbia |
South Africa |
Thailand |
Ukraine |
United States |
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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
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The end of trial is defined in the protocol as LPLV. The study is on hold globally pending further discussion on the paediatric program with regulatory agencies. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |