| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Complicated Intra-Abdominal Infection |
|
| E.1.1.1 | Medical condition in easily understood language |
| Complicated Intra-Abdominal Infection |
|
| 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 | LLT |
| E.1.2 | Classification code | 10056570 |
| E.1.2 | Term | Intra-abdominal infection |
| 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 evaluate the safety of tigecycline versus a ceftriaxone regimen in the treatment of pediatric subjects (ages 8 to 17 years) with selected serious infections (cIAI). |
|
| E.2.2 | Secondary objectives of the trial |
| 1. To evaluate clinical and microbiological efficacy of tigecycline in the pediatric population. 2. To evaluate the PK and PD profiles of tigecycline in pediatric subjects with cIAI. 3. To obtain in vitro susceptibility data on tigecycline for a range of bacterial pathogens isolated from subjects with cIAI. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Male or female subjects 8 to 17 years old. Children with bone maturation less than 8 years old should be enrolled with caution due to potential risk of tooth discoloration. 2. Have a diagnosis of a serious infection (cIAI) requiring hospitalization and administration of IV antibiotic therapy. 3. Anticipated length of antibiotic therapy greater than or equal to 5 days. 4. The following criteria must also be satisfied: a) Be scheduled for or within 48 hours before screening have had a laparotomy, laparoscopy, or transrectal or percutaneous drainage of an intra-abdominal abscess. b) Have a cIAI which would include clinical entities such as (the following are examples): - complicated appendicitis [e.g., gangrenous, perforation (grossly visible) and abscess and/or periappendicular abscess]; - purulent peritonitis or peritonitis associated with fecal contamination; - intra-abdominal abscess, including those that develop in a post-operative subject; and - viscus perforation (with evidence of peritonitis or intra-abdominal abscess) with symptoms lasting at least 12 hours before operation. c) Have at least 1 of the following signs of systemic infection: - fever (within the 24 hours before randomization) defined as a core temperature >38.5 degree C or <36 degree C (other methods are accepted); - white blood cell (WBC) count >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; and - 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). d) Have at least 2 of the following signs and symptoms: - abdominal tenderness or pain; - abdominal mass on physical examination; - ileus or hypoactive bowel sounds; and - evidence or suspicion of an intra-abdominal abscess by radiography, scintigraphy, ultrasonography, computerized tomography (CT) scan, or magnetic resonance imaging (MRI). 5. 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. |
|
| E.4 | Principal exclusion criteria |
| 1. Subject with any concomitant illness/condition 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 (e.g., life expectancy <30 days). 2. Received more than 24 hours of potentially effective systemic antibiotic therapy before first dose of test article (except if for prophylactic/perioperative use) to treat the current 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: Subject may not have failed therapy with any antibiotic where cross resistance would be expected with an antibiotic used in this study. 3. Infection due to a pathogenic organism known or suspected to be resistant to the study related antibiotics the subject may receive (e.g., before test article administration). 4. Subjects with any of the following conditions: - viscus perforation without evidence of peritonitis or intra-abdominal abscess; - pelvic inflammatory disease (any infection of the female genital-urinary track); - endocarditis; - infected device that will not be removed; - cystic fibrosis; - active tuberculosis; - congenital immunodeficiency; - meningitis; - severe sepsis; - refractory shock (e.g., in which hemodynamic parameters cannot be maintained despite adequate volume replacement); - confirmed malignancy in a subject receiving active course(s) of chemotherapeutic agents; - known or suspected infection with human immunodeficiency virus (HIV) (e.g., positive HIV antibody); - known or suspected concomitant infection requiring systemic treatment; - suspected inflammatory bowel disease. 5. Contraindication or hypersensitivity to any of the test articles that the subject may receive, including tetracycline (e.g., anaphylaxis). 6. 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. 7. Concurrent hemodialysis, hemofiltration, peritoneal dialysis, or plasmapheresis. 8. 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 the upper limit of normal (ULN); and - Bilirubin >3 x ULN, unless isolated hyperbilirubinemia is directly related to the acute process. 9. Participated in any investigational studies of drugs or devices within 4 weeks before administration of the first dose of test article. 10. Pregnant or nursing female. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The assessment of safety of tigecycline versus ceftriaxone is the primary objective of this study. Safety will be evaluated by collection of adverse events, laboratory assessments, physical examinations, vital signs measurements and electrocardiograms. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Clinical response (cure, failure, or indeterminate) at the TOC for 2 co-primary populations: the clinically evaluable (CE) and clinical modified Intent-to-Treat (c-mITT) populations |
|
| E.5.2 | Secondary end point(s) |
| Clinical response at the IV LDOT and FUP visits for co-primary populations: the CE and c-mITT populations and the microbiological response at the subject level and microbiological response at the pathogen level, response rate by pathogen and MIC value, response rates for polymicrobial/monomicrobial infections, and susceptibility evaluations. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Clinical response at the IV LDOT and FUP visits for co-primary populations: the CE and c-mITT populations and the microbiological response at the subject level and microbiological response at the pathogen level, response rate by pathogen and MIC value, response rates for polymicrobial/monomicrobial infections, and susceptibility evaluations. |
|
| 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 | 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 |
|
| 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 |
|
| 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 |
| Israel |
| Korea, Republic of |
| Mexico |
| Oman |
| Panama |
| Peru |
| Qatar |
| Russian Federation |
| Serbia |
| 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 trial is defined in the protocol as LPLV. The study is on hold globally pending further discussion on the paediatric program with regulatory agencies. |
|
| 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 |
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