| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Treatment of adult patients with complicated skin and skin structure infections requiring hospitalization. |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | Information not present in EudraCT |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To compare the safety, tolerance and efficacy of parenteral RO4908463 to the “standard of care” in patients with complicated skin and skin structure infections requiring hospitalization. |
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| E.2.2 | Secondary objectives of the trial |
1.To obtain in vitro susceptibility data vs RO4908463 on MRSA and other pathogenic organisms isolated from patients participating in the study.
2.To evaluate the pharmacokinetics of RO4908463 in the patient population including the influence of covariates
3.To explore the relationship of drug exposure to clinical cure rates in the bacteriologically evaluable patients
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| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Informed consent has been signed by patient or has been signed by a legal representative recognized by the local authority
2. Male or female patients ≥18 years of age with skin or skin structure infection requiring hospitalization
3. If the patient is sexually active and is female of child bearing potential, or is a sexually active male who has a female partner of child bearing potential, then the patient agrees to use two forms of contraception, at least one of which is a barrier method, during the study period (Baseline to EOSE)
4. If infection site is contiguous to bone or if septic thrombophlebitis is suspected, then an appropriate imaging modality [MRI, CT, bone scan] of the area must show no evidence of osteomyelitis/thrombophlebitis within 24 hours of randomization
5. Appropriate culture specimen (obtained by tissue biopsy, deep culture, needle aspiration, incision and drainage, or curettage) has been obtained for culture and sensitivity prior to administration of IV study drug. If anaerobes are suspected the specimen must be transported to the local lab in appropriate transport media (or if material is aspirated with a syringe, air must be expelled, the needle recapped using a one hand technique and transported immediately to the local lab for processing). Alternatively, commercially available anaerobic transport swabs can be used.
6. Patients must have a clinical diagnosis of one of the following skin and skin structure infections caused by bacteria known or suspected to be susceptible to the randomized study treatments
a)extensive cellulitis (> 10 cm) and purulent drainage or purulent fluid collection demonstrating PMN’s and/or bacteria on Gram stain requiring parenteral antibiotics
b)extensive abscess and infection of deep soft tissue requiring parenteral antibiotics and surgical incision and drainage or debridement [If clinical evidence of septic thrombophlebitis is present, then appropriate imaging to exclude septic thrombophlebitis is required within 24 hours of randomization.]
c) post traumatic wound infection (without evidence of contiguous osteomyelitis)
d) surgical site infection
e) infected burn
7. Material from the site of infection is clinically purulent or seropurulent
8. The patient has received <24 hours of antibacterial therapy prior to study entry
Or
Patient has received ≤ 3 days of prior antibiotic therapy and has clinical evidence of treatment failure (such evidence includes continued fever and the persistence of other symptoms consistent with skin and skin structure infections) and a Gram stain obtained by an acceptable method demonstrates bacteria
Or
The infecting organism is known to be resistant to the previous antibacterial therapy
9. Have had a temperature > 37.5 °C oral or > 37.9 °C tympanic or > 38.3 °C rectal during the previous 24 hours
10. Have at least two of the following:
a) WBC count > 10,000 mm3 or with ≥ 10% bands;
b) local erythema;
c) local swelling;
d) tenderness;
e) fluctuance;
f) regional lymphangitis
|
|
| E.4 | Principal exclusion criteria |
1. Have presented with sustained shock, defined as systolic blood pressure < 90
mm Hg for > 2 hours despite adequate fluid resuscitation, with evidence of
hypoperfusion or the need of sympathomimetic agents to maintain blood pressure
2. Are likely to be discharged in less than 3 days
3. Require hemodialysis, peritoneal dialysis, plasmapheresis or hemoperfusion
4. Have known or suspected osteomyelitis contiguous to the site of skin/skin structure
infection
5. Have known or suspected septic thrombophlebitis
6. Have known or suspected fungal, mycobacterial, viral or parasitic infection
7. Have an infected full thickness burn of any size or burn > 30% body surface area
8. Are using or likely to use topical antibiotics (except for the routine care of
intravascular catheters or indwelling bladder urinary catheters)
9. Have received an investigational drug within one month prior to enrollment
10. Have a known or suspected concomitant bacterial infection requiring antibiotic
treatment
11. Have a skin infection or chronic non-healing ulcer > 2 weeks duration
12. Are patients in whom surgery is the primary treatment, e.g. likely to require
surgical extirpation of an infected artery, vein or arterial graft, amputation of the
infected area or limb or necrotizing fasciitis. (Amputation of gangrenous toes
adjacent to an infection site is permitted)
13. Require chronic immunosuppressive therapy or have an anticipated need for
immunosuppressive therapy for > 1 month from baseline (including > 10 mg/day of
systemic prednisone or equivalent)
14. Have any form of epilepsy or history of seizures
15. Have hypersensitivity to β-lactam antibiotics
16. Have a history of a significant reaction to vancomycin and the site assigned
comparator is vancomycin
17. Have a history of significant hypersensitivity reaction to the initial Gram-negative
antibiotic therapy (aztreonam or ciprofloxacin)
18. Have a history of cerebrovascular accident, transient ischemic attack(s), brain
metastases, space occupying lesion in the CNS or systemic malignancy within past
year and/or are currently receiving adjuvant chemotherapy
19. Have a creatinine clearance, using the Cockcroft-Gault equation, of ≤ 80 mL/min
20. Have significant proteinuria (4+ or > 1.0 % or 10 g/L on urinalysis)
21. Have evidence of liver dysfunction manifested by: ALT or AST ≥ 4X ULN or total
bilirubin > 1.5X ULN
22. Have neutropenia (ANC < 1000/mm3) or platelet count < 50,000/mm3
23. Have a history of hemolytic anemia
24. Is unlikely to comply with the dosing regimen, scheduled assessments, or complete
the study for any other reason
25. Have artificial heart valves, artificial joints or vascular prostheses
26. Are receiving or likely to receive coumarin or probenecid therapy during the study
27. Have known HIV infection or AIDS with a CD4 count < 250 cells/mm3 OR are taking antiretroviral therapy or in the opinion of the investigator should begin antiretroviral treatments or have undiagnosed HIV infection but have clinical findings highly suggestive of HIV
28. Are pregnant or nursing
29. Have any concomitant condition which could preclude evaluation of response or make it unlikely that a course of therapy and follow-up evaluations could be completed
30. Have previously been randomized into this study or are ancillary personnel involved with this study
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| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary efficacy variable is the clinical cure rate at the EOSE visit as determined by a central blinded third party evaluator.
(Sec section 8.1 of protocol) |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| 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 | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| 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.8.5 | 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
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
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