| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Subjects with diabetes with a qualifying foot 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 relative safety and clinical efficacy of a once-daily dose of tigecycline versus ertapenem in the treatment of subjects with diabetic foot infections.
|
|
| E.2.2 | Secondary objectives of the trial |
1. To evaluate the microbiologic efficacy of tigecycline.
2. To obtain in vitro susceptibility data on tigecycline for a range of bacterial pathogens isolated from diabetic foot infections.
3. To compare health care resource utilization between treatment arms.
4. To examine the pharmacokinetic profile of tigecycline in subjects with diabetic foot
infections after once-daily administration and after prolonged administration.
5. To evaluate the safety and efficacy of a once-daily dose of tigecycline in the treatment of subjects who are identified as having a diabetic foot infection with confirmed osteomyelitis. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Hospitalized male or female subjects >=18 years of age.
2. Subjects with diabetes mellitus per the American Diabetes Association (ADA) criteria.
3. Subjects with a foot infection that does not extend above the knee. If multiple infections meet all criteria below, the one with the highest IWGDF PEDIS grade for infection will be designated as the target.
4. Subjects with a foot infection that meets all of the following IWGDF PEDIS classifications (note: an ulcer is not required):
· Perfusion: grade 1 or 2;
· Infection: grades 2 to 4.
5. Subjects with anticipated need for IV antibiotic therapy of 5 days or longer.
6. Subjects whose foot infection has had an acute onset or worsening of signs and symptoms within the past 14 days.
7. Subjects who have received <= 48 hours administration of a potentially effective antibiotic (ie, active against all pathogens known to be present) to treat the current target infection.
8. Subjects who are considered to be therapeutic failures of prior antibiotic therapy with another agent may be enrolled if they have had worsening or no improvement in the clinical signs and symptoms of their diabetic foot infection and either have 1) a Gram stain from the infection site showing white blood cells and a potential pathogen or 2) culture results showing a pathogen resistant to prior antibiotics. Note: Subject may not have failed one of the study medications or any agent of the same class.
9. Osteomyelitis substudy arm only: Subjects who have presumptive evidence of osteomyelitis, defined as visible bone, a positive radiograph (ie, demineralization,
periosteal reaction, and bony destruction), or a positive probe-to-bone finding (as
described by Grayson et al) or confirmed evidence of osteomyelitis, defined as positive MRI (eg, decreased marrow signal on T1-weighted images, increased marrow signal on T2-weighted images, and contrast enhancement on T1-weighted postcontrast images) or positive bone biopsy. |
|
| E.4 | Principal exclusion criteria |
1. Necrotizing fasciitis, crepitant cellulitis, wet gangrene, gas gangrene, ecthyma
gangrenosum, or severely impaired arterial supply to any portion of the affected foot.
2. Infected prosthetic materials or devices that will not be removed.
3. Suspected or known infection with a pathogen resistant to tigecycline or ertapenem ± vancomycin (eg, P. aeruginosa).
4. Subjects with
a. a diabetic foot infection without presumptive evidence of osteomyelitis (as
defined above) who are anticipated to need > 28 days of antibiotic treatment.
(primary study arm)
OR
b. a diabetic foot infection with presumptive evidence of osteomyelitis (as defined
above) who are anticipated to need > 42 days of antibiotic treatment.(osteomyelitis substudy arm)
5. Anticipated requirement for complete resection or amputation (ie, removal of all infected tissue with clean margins) of the infected anatomical site within 1 month (30 days).
Note: Subjects who will have all infected bone removed, but still have a skin infection
may be randomized to the primary study arm after the removal of the infected bone.
6. Concurrent hemodialysis, hemofiltration, peritoneal dialysis or plasmapheresis.
7. 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 (eg, life expectancy < 30 days).
8. Subjects with contraindication or hypersensitivity to any of the test articles or related antibiotics.
9. Presence of any of the following laboratory findings:
a. Neutropenia with absolute neutrophil count <1 x 10x9/L [<1000/mm3]
b. Presence of significant hepatic disease:
i. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) >10 x the upper limit of normal (ULN);
ii. Total bilirubin > 3 x the ULN;
iii. Acute hepatic failure or acute decompensation of chronic hepatic failure.
c. Creatinine clearance (ClCR) < 30 mL/min, Creatinine clearance may be calculated
from the serum creatinine (SCR) concentration by the following equation:
Male: ClCR mL/min = (140-age) x weight (kg) / (72 x SCR [mg/dL])
Female: ClCR mL/min = 0.85 x ([140-age] x weight [kg] / [72 x SCR {mg/dL}]).
10. Known or suspected concurrent infection that would require treatment with a systemic antibacterial agent(s).
11. Any investigational drugs taken or investigational devices used within 4 weeks before the first dose of IV test article administration.
12. Previous participation in this study.
13. Pregnant or breastfeeding women.
14. Women of childbearing potential who do not agree either to practice sexual abstinence or use a medically acceptable method of contraception throughout the duration of the study and for at least 1 month (30 days) after the last day of IV test article administration. A woman of childbearing potential is one who is biologically capable of becoming pregnant; this includes women who are using contraceptives or those women whose sexual partners are either considered sterile or using contraceptives.
15. Subjects taking immunosuppressive therapy, defined as chronic treatment with known immunosuppressive medications (including the use of > 40 mg of prednisone or its equivalent per day for >3 weeks before randomization), or any severely
immunocompromised subjects. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary efficacy endpoint will be the clinical response rate at the Test-of-cure (TOC) visit for 2 co-primary populations: the Clinically evaluable (CE) population and the Clinical modified intent-to treat (c-mITT) population. |
|
| 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 | Yes |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| 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.8.3 |
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 | 2 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 70 |
| 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 | 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 the study is the last visit of the last subject. |
|
| 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 | 20 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 20 |
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