E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Complicated intra-abdominal infections (cIAI), complicated skin and skin structure infections (cSSSI), community-acquired pneumonia (CAP). |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056570 |
E.1.2 | Term | Intra-abdominal infection |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040872 |
E.1.2 | Term | Skin infection |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10010120 |
E.1.2 | Term | Community acquired pneumonia |
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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 |
To determine the pharmacokinetic profile and to evaluate the safety and tolerability of ascending multiple doses of tigecycline in patients aged 8 to 11 years with selected serious infections (cIAI, cSSSI, CAP). |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Male or female patients aged 8 to 11 years, inclusive. 2) Willing and able to complete all activities required for the study. 3) Anticipated length of antibiotic therapy ≥ 5 days. 4) Have a diagnosis of a serious infection (eg, cIAI, cSSSI, or CAP) requiring hospitalization and administration of IV antibiotic therapy. 5) Specific criteria must also be satisfied for each specific sites of infection. (a) For patients with cIAI: · Be scheduled for or (within 48 hours before screening) have undergone a laparotomy, laparoscopy, or transrectal or percutaneous drainage of an intra-abdominal abscess. · Have a cIAI such as the following: - appendicitis complicated by perforation (grossly visible) and/or abscess; - purulent peritonitis or peritonitis associated with fecal contamination; - intra-abdominal abscess; - viscus perforation with symptoms lasting at least 12 hours before operation. · Have at least 2 of the following signs and symptoms: - abdominal tenderness or pain; - abdominal mass on physical examination; - ileus or hypoactive bowel sounds; - severe nausea and/or vomiting - evidence or suspicion of an intra-abdominal abscess or viscus perforation by radiography, scintigraphy, ultrasonography, computed tomography (CT), or magnetic resonance imaging (MRI) (b) For patients with cSSSI: · Have a cSSSI requiring significant surgical intervention or involving deeper soft tissue. This would include clinical entities such as the following: - infected ulcers or wounds that have developed signs of erythema, swelling, fluctuance, tenderness, pus, or warmth; - burns (< 20% body surface area, nonfull-thickness); - major abscess (not treatable through surgery alone); - deep or extensive cellulitis, either in an underlying disease state or > 10 cm in width or length (where anatomically applicable); - peripheral IV catheter sites with documented purulent drainage, provided that the catheter line will be removed; - infected human or animal bites. · Have at least 2 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. (c) For patients with CAP: · Suspected bacterial rather than viral pneumonia. · Chest radiograph (posteroanterior/anteroposterior and if possible lateral views) within 48 hours before the first administration of IV test article showing the presence of an infiltrate. · Presence of at least 2 of the following: - dyspnea or tachypnea (respiratory rate > 30 breaths per minute); - cough; - production of purulent sputum or a change in sputum character consistent with bacterial infection; - auscultatory findings of rales and/or evidence of pulmonary consolidation (dullness on percussion, bronchial breath sounds or egophony); - hypoxemia with partial pressure of oxygen (PO2) < 60 mm Hg or oxygen saturation < 90% while the patient is breathing room air, as determined by pulse oximetry or arterial blood gas (ABG); - leukocytosis (white blood cell count [WBC] > 13 × 109/L [13,000/mm3]); OR > 15% immature neutrophils (bands); OR leukopenia with total WBC < 4.5 × 109/L (4,500/mm3). · The presence of either of the following: - fever (within the 24 hours before “randomization”/enrollment), defined as a rectal/core temperature > 38°C/100.4°F, oral temperature > 37.5°C/99.5°F, or axillary temperature > 37.2°C/99°F OR hypothermia, defined as rectal/core body temperature < 35°C/95°F |
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E.4 | Principal exclusion criteria |
1) Patients with any concomitant condition or taking any concomitant medication that, in the opinion of the investigator, could preclude an evaluation of safety or efficacy responses or make it unlikely that the anticipated course of therapy or follow-up assessment will be completed (eg, life expectancy < 30 days). 2) For cSSSI patients, the presence of decubitus ulcers, necrotizing fasciitis, gas gangrene, or skeletal infection. 3) Endocarditis; presence of an artificial heart valve or infected device that will not be removed. 4) CAP patients who have been hospitalized within 14 days before the onset of symptoms. 5) Patients with any of the following conditions: - Cystic fibrosis. - Active tuberculosis. - Congenital immunodeficiency. - Meningitis. - Septic shock. - Osteomyelitis (suspected or evident). - Refractory shock syndrome in which hemodynamic parameters cannot be maintained despite adequate supportive therapy. - Confirmed malignancy with patient receiving an active course of chemotherapeutic agents. - Known or suspected infection with human immunodeficiency virus (HIV) or positive test result for HIV antibody. - Known or suspected concomitant bacterial or parasitic infection requiring systemic treatment. 6) Presence of any of the following for patients with pneumonia: - Postobstructive pneumonia. - Pulmonary abscess. - Empyema. - Known or suspected pulmonary infection with Pneumocystis carinii. 7) Known or suspected hypersensitivity to tigecycline or other compounds related to this class of antibacterial agents (ie, tetracyclines). 8) Known or suspected P. aeruginosa infection. 9) Patients receiving immunosuppressive therapy that, in the opinion of the investigator, would decrease the patient’s ability to eradicate the infection, including the use of high-dose corticosteroids (eg, chronic [for ≥ 3 weeks before “randomization”/enrollment] use of > 10 mg of prednisone adult equivalent per day). 10) Receipt of an organ or bone marrow transplant. 11) Presence of any of the following laboratory findings: - Neutropenia (absolute neutrophil count < 1 × 109/L [< 1000/mm3]). - Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 10 × the upper limit of normal (ULN) or bilirubin > 3 × ULN, unless isolated hyperbilirubinemia is directly related to the acute process (for patients with cIAI). 12) Pregnant or breastfeeding female patients and female patients of childbearing potential (ie, female patients are either biologically capable of becoming pregnant or have started their menses) who are unable or unwilling to take adequate contraceptive precautions. 13) Previous participation in this clinical trial. 14) Receipt any investigational drugs or devices (defined as lacking regulatory agency within 4 weeks before administration of the first dose of tigecycline. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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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last visit of the last subject |
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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 | |
E.8.9.1 | In the Member State concerned months | 12 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 12 |