| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| COMPLICATED SKIN AND SKIN STRUCTURE 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 the safety and efficacy of tigecycline with that of the comparator in treating subjects with complicated skin and/or skin structure infection (cSSSI). |
|
| E.2.2 | Secondary objectives of the trial |
(1) To compare the microbiologic efficacy of tigecycline with that of the comparator in the microbiologically evaluable (ME) population;
(2) to evaluate in vitro susceptibility data on tigecycline for a range of pathogenic bacteria that cause cSSSI; and
(3) to compare health care utilization between the treatment groups. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Male and female subjects, 18 years of age or older.
2. Anticipated need for in-patient intravenous antibiotic therapy of 4 days or longer.
3. Male or non-pregnant, non-lactating 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). A woman of childbearing potential is one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives. Effective contraception should have been in place for at least 2 months prior to study entry. All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control or sexual abstinence for the duration of the study and for 30 days after the last dose of Test Article.
4. A serum or urine laboratory pregnancy test must be negative at baseline for all women of childbearing potential. A woman of childbearing potential is one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives.
5. Subjects known or suspected to have a complicated skin and skin structure infection. Complicated skin/skin structure infection includes infections involving deeper soft tissue or requiring significant surgical intervention, or a significant underlying disease state (such as diabetes mellitus, peripheral vascular disease, peripheral neuropathy, venous insufficiency) that complicates response to treatment. This would include clinical entities such as one of the following:
a. Infected ulcers that have developed signs of erythema, swelling, tenderness, pus or warmth.
b. Burns (<5% body surface area, non-full thickness).
c. Major abscess (not treatable through surgery and wound care alone).
d. Deep or extensive cellulitis either in an underlying disease state or greater than 10 cm in width or length where anatomically feasible, or the presence of drainage or discharge.
e. Peripheral intravenous catheter sites with documented purulent drainage, provided the catheter line will be removed.
f. Infected human or animal bites.
6. Subjects must have at least two of the following signs and symptoms:
a. Drainage and/or discharge.
b. Fever defined as an oral temperature > 37.8° C (100° F), a tympanic temperature > 38.2° C (100.8° F), or a rectal temperature >38.4° C (101.0° F) or hypothermia defined as an oral, tympanic or axillary temperature < 35.5° C (95.9° F), or a rectal temperature < 36.0° C (96.8° F), within the 24 hours prior to enrollment.
c. Erythema.
d. Swelling and/or induration.
e. Localized warmth.
f. Pain and/or tenderness to palpation.
g. Leukocytosis defined as white blood cell count (WBC) >10,000/mm3, or >10% immature (band) forms.
7. Subjects who have not received more than two doses of any given non-study antibacterial drug after the original culture of the infected site was obtained except for subjects considered prior antibiotic failures.
8. For subjects who are considered therapeutic failures for prior antibiotic therapy with another agent at entry, a baseline culture of the infected site must be obtained before the first dose of Test Article is administered (see Section 12.0, Prior Treatment).
9. An IRB or IEC approved, signed, and dated informed consent form before any screening procedures are performed that are specific to the study. If any subject is unable to give consent, it may be obtained from the subject’s next of kin or legal representative in accordance with local laws and regulations. If or when the subject is able to give consent, it must then be obtained. |
|
| E.4 | Principal exclusion criteria |
1. Subjects with any concomitant condition that, in the opinion of the investigator, would preclude an evaluation of a response or make it unlikely that the contemplated course of therapy could be completed.
2. An uncomplicated skin and/or skin structure infection (eg, simple abscesses, folliculitis, impetiginous lesions, furunculosis, superficial cellulitis).
3. Subjects with a skin and/or skin structure infection that can be treated by surgery and wound care alone.
4. Clinical presence or suspicion of any of the following:
a. Ecthyma gangrenosum.
b. Necrotizing fasciitis or gangrene.
c. Osteomyelitis or septic arthritis contiguous to the infected site.
d. Crepitant cellulitis (gas gangrene).
5. Subjects with severely impaired arterial blood supply and insufficiency such that the likelihood of amputation of the infected anatomical site within 1 month is likely.
6. Infected chronic diabetic foot ulcers or decubitus ulcers where the documented infection is present for >1 week.
7. Presence of any known or suspected concomitant bacterial infection requiring additional systemic antimicrobial therapy. Subjects with suspected or known Pseudomonas aeruginosa infections. However, subjects in whom the initial wound culture shows evidence of P aeruginosa infection may continue to receive Test Article at the investigator’s discretion if the subject shows signs of substantial and continuous clinical improvement on a daily basis.
8. Subjects with underlying immunodeficiency disease or subjects requiring chronic treatment with known immunosuppressant medications that, in the opinion of the investigator, would decrease the subjects’ ability to eradicate the infection (eg, systemic corticosteroids equivalent to >40 mg/day of prednisone).
9. Concurrent plasmapheresis or hemoperfusion.
10. Known or suspected hypersensitivity to tigecycline, beta-lactams (ampicillin or amoxicillin), sulbactam, clavulanate, vancomycin, teicoplanin, or tetracycline- or comparator-like drugs.
11. Presence of any of the following laboratory findings:
a. Neutropenia (absolute neutrophil count [ANC] <1000/mm3);
b. Presence of hepatic disease:
· Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels >10 x upper limit of normal (ULN) values.
· Bilirubin level >3.0 x ULN.
· Subjects with acute hepatic failure or acute decompensation of chronic hepatic failure are excluded.
c. Creatinine clearance of <30 mL/min after adequate hydration. Creatinine clearance (Clcr) may be estimated from the serum creatinine (Scr) concentration by the following equation:
Male: Clcr = [(140-age) x weight (kg) mL/min]/ 72 x Scr (mg/dL)]
Female: Clcr = 0.85 x Clcr derived by the above formula
12. Subjects with prior or planned concomitant treatment with probenecid within 7 days; or any investigational drugs taken within 4 weeks before administration of the first dose of TA (Day 1).
13. Previous participation in this study. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint will be the clinical response in the clinically evaluable (CE) population at the test-of-cure (TOC) visit. |
|
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| 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 | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 33 |
| 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 | 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
|
| 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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