| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Complicated Intra-Abdominal Infection |
|
| MedDRA Classification |
| 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 compare safety and noninferiority of the clinical efficacy of tigecycline administered as an initial dose of 100 mg followed by 50 mg every 12 hours to that of ceftriaxone sodium 2 g once daily plus metronidazole 1 g to 2 g daily administered in divided doses for the treatment of hospitalized subjects with cIAI. |
|
| E.2.2 | Secondary objectives of the trial |
(1) To compare the microbiological efficacy of tigecycline to ceftriaxone plus metronidazole in the microbiologically evaluable population;
(2) to evaluate in vitro susceptibility data on tigecycline for a range of pathogenic bacteria that cause complicated intra-abdominal infection; and
(3) to compare health care utilization between the treatment groups. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Hospitalized male or female subjects, ≥18 years of age.
2. Male or nonpregnant, nonlactating female who is postmenopausal, surgically sterilized, or is using reliable method of birth control (eg, hormonal birth control, intrauterine device [IUD], double barrier [male condom, female condom, diaphragm] or a barrier method plus a spermicidal agent [contraceptive foam, jelly, or cream] or abstinence).
3. A serum or urine laboratory pregnancy test must be negative at baseline for all women of childbearing potential.
4. Subjects must be scheduled for, or have had, exploration via laparotomy, laparoscopy or percutaneous drainage indicated by the presence or suspicion of an intra-abdominal infection within 1 calendar day prior to, or after, the first dose of test article.
5. Subjects known or suspected to have at least one of the following intra-abdominal infections or conditions of less than two weeks’ duration:
a. Intra-abdominal abscess, including liver and spleen abscess that develops in a post-operative subject.
b. Appendicitis complicated by perforation (grossly visible) and abscess and/or periappendiceal abscess.
c. Perforated diverticulitis complicated by abscess formation or fecal contamination.
d. Perforation of the large or small intestine with abscess or fecal contamination.
e. Purulent peritonitis or peritonitis associated with fecal contamination.
f. Gastric or duodenal perforation with symptoms lasting at least 24 hours prior to operation.
g. Posttraumatic bowel perforation with symptoms lasting at least 12 hours prior to operation.
h. Complicated cholecystitis with evidence of perforation or empyema.
6. Minimal clinical criteria at the time of intra-abdominal infection diagnosis include the presence of either:
· Fever defined as an oral, tympanic or axillary temperature >=38.0°C/100.4°F or a rectal/core temperature >=38.5°C/101.3°F or hypothermia defined as an oral, tympanic or axillary temperature <35.5°C/95.9°F or a rectal/core temperature <36.0°C/96.8 F
--or--
· Leukocytosis defined as white blood cell count (WBC) >10,000/mm3, or leukopenia defined as WBC <5000/mm3, or >10% immature (band) forms.
Plus at least 2 of the following signs and symptoms:
· Localized or diffuse abdominal wall rigidity and/or involuntary guarding.
· Abdominal tenderness or abdominal pain.
· Nausea or vomiting or ileus.
· Radiographic, scintigraphic, sonographic, computed tomographic (CT), or magnetic resonance imaging studies suggesting a perforated viscus, an intra-abdominal abscess, or other focus of intra-abdominal infection. |
|
| E.4 | Principal exclusion criteria |
1. Subjects with underlying immunodeficiency disease or subjects requiring chronic treatment with known immunosuppressant medications that, in the opinion of the investigator, would decrease the subject’s ability to eradicate the infection, including the use of systemic corticosteroids (eg, >5 mg/day prednisone). (Note: physiological replacement doses; stress doses of steroids up to 3 days surrounding surgery; and inhaled steroids are permitted.).
2. Active or treated leukemia within the past year; or systemic malignancy that required treatment with chemotherapy, immunotherapy, radiation therapy, or antineoplastic therapy within the past 3 months or which is anticipated to begin prior to the test-of-cure (TOC) visit; or any known or suspected malignancy to the abdomen.
3. Concurrent hemodialysis, peritoneal dialysis or subjects with indwelling peritoneal catheters or shunts, plasmapheresis or hemoperfusion.
4. Subjects with any concomitant conditions that, in the opinion of the investigator, would preclude an evaluation of a response or make it unlikely that the contemplated course of therapy or TOC visit could be completed.
5. Presence of any known or suspected concomitant bacterial or fungal infection requiring systemic antimicrobial therapy treatment at a site other than the abdomen (eg, bacterial pneumonia, urinary tract infection [UTI]); or intra-abdominal infection due exclusively to fungi).
6. Anticipation of using a post-surgical open abdominal technique (ie, leaving the fascia and/or muscular layers open) or expectation of planned abdominal re-exploration either in or out of the operating room.
7. Subjects suspected preoperatively to have a diagnosis of spontaneous bacterial peritonitis, simple cholecystitis, gangrenous cholecystitis without rupture, simple appendicitis, acute suppurative cholangitis, pancreatic abscess or infected pancreatic/peri-pancreatic necrosis in association with necrotizing pancreatitis.
8. Subjects with intra-abdominal infection known or suspected to be caused by one or more organism(s) which are not susceptible to either of the test articles (eg, methicillin-resistant staphylococci [MRSA, MRSE], Pseudomonas aeruginosa, etc) and which, in the investigator’s opinion, requires treatment with an additional antibacterial agent.
9. Subjects who have received more than 1 day of systemic antibacterial therapy prior to study entry unless declared a failure.
10. Subjects who will require prolonged therapy (test article for >14 days).
11. Subjects with prior or planned concomitant treatment with probenecid within 7 days; or any investigational drugs within 1 month prior to administration of the first dose of test article.
12. At time of first dose of test article, presence of sustained shock, defined as systolic blood pressure <90 mmHg for >2 hours with evidence of hypoperfusion despite adequate fluid resuscitation, or the need for sympathomimetic agents to maintain blood pressure.
13. Known or suspected hypersensitivity to, or a known or suspected adverse reaction to tigecycline, tetracycline agents, ceftriaxone sodium, cephalosporins, metronidazole, nitroimidazole derivatives or other compounds related to these classes of antibacterial agents.
14. Presence of any of the following laboratory findings:
· Neutropenia defined as absolute neutrophil count (ANC) <1000/mm3.
· Thrombocytopenia defined as platelet count <35,000/mm3.
· Aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase (AP) >10 times the upper limit of normal (ULN).
· Bilirubin >3 times the ULN, unless isolated hyperbilirubinemia was directly related to the acute process.
· Creatinine clearance of <20 mL/min/1.73m2 after adequate hydration.
15. Subjects with acute, severe organ system failure (cardiac, renal, or hepatic failure, or septic shock) or whose life expectancy is <30 days.
16. Anticipated discharge from the hospital in less than 4 days or the likelihood that the subject will not complete the course of treatment.
17.Previous participation in this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint will be clinical response in the clinically evaluable population at the TOC assessment. |
|
| 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 | Information not present in EudraCT |
| 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 | 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) | Yes |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| 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 study is the last visit of the last subject or 15 days after the last subject receives the last dose of test article, whichever is later. The clause "or 15 days after the last subject receives the last dose of test article" was added in the case that the last patient may have been lost to follow-up and did not return for a final visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
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