A Phase 3 Randomized, Double-Blind, Multicenter Study Comparingthe Efficacy and Safety of 6-Day Oral TR-701 Free Acid and 10-DayOral Linezolid for the Treatment of Acute Bacterial Skin and SkinStructure Infections

Conditions: Acute Bacterial Skin and Skin Structure Infections
MedDRA version: 12.1Level: LLTClassification code 10040872Term: Skin infection

Registration Number: EUCTR2010-022168-11-SK

Lead Sponsor: Trius Therapeutics, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 658

Inclusion Criteria

1. Males or females = 18 years old
2. ABSSSI meeting at least 1 of the clinical syndrome definitions listed below and requiring systemic oral antibiotic therapy. Local symptoms must have started within 7 days before the Screening Visit.
A. Cellulitis/erysipelas defined as a diffuse skin infection, characterized by all of the
following within 24 hours:
? Rapidly spreading areas of erythema of a minimum surface area of 75 cm2
? No collection of pus apparent upon visual examination (diagnosis still consistent with cellulitis/erysipelas if pus is collected from the lesion)
? At least 1 of the following signs of infection:
? Induration
? Localized warmth
? Pain or tenderness on palpation
? Swelling
? At least 1 of the following systemic signs of infection:
? Lymph node tenderness and increase in volume or palpable proximal to the
primary ABSSSI
? Fever, defined as body temperature = 38°C (100.4°F) oral, = 38.5°C (101.2°F)
tympanic, or = 39°C (102.2°F) rectal (observed by a health care provider)
? White blood cell (WBC) count = 10,000 cells/mm3 or < 4000 cells/mm3
? > 10% immature neutrophils
B. Major cutaneous abscess defined as an infection characterized by a collection of pus within the dermis or deeper that is accompanied by all of the following within 24 hours:
? Erythema extending at least 5 cm from the peripheral margin of the abscess
? At least 1 of the following signs of infection:
? Fluctuance
? Incision and drainage required
? Purulent or seropurulent drainage
? Localized warmth
? Pain or tenderness on palpation
? At least 1 of the following systemic signs of infection:
? Lymph node tenderness and increase in volume or palpable proximal to the
primary ABSSSI
? Fever, defined as body temperature = 38°C (100.4°F) oral, = 38.5°C (101.2°F)
tympanic, or = 39°C (102.2°F) rectal (observed by a health care provider)
? WBC count = 10,000 cells/mm3 or < 4000 cells/mm3
? > 10% immature neutrophils
C. Wound Infection defined as an infection of any apparent break in the skin characterized by the following:
? Superficial incisional SSI meeting all of the following criteria:
? Follows clean surgery (elective, not emergency, nontraumatic, primarily closed,
no acute inflammation; no break in technique; respiratory, gastrointestinal,
biliary, and genitourinary tracts not entered)
? Involves only the skin or subcutaneous tissue around the incision, does not
involve fascia
? Occurs within 30 days after procedure
? Original surgical incision = 3 cm
? Purulent drainage from a wound with surrounding erythema extending at least 5
cm from the peripheral margin of the wound
? At least 1 of the following systemic signs of infection:
- Lymph node tenderness and increase in volume or palpable proximal to the
primary ABSSSI
- Fever, defined as body temperature = 38°C (100.4°F) oral, = 38.5°C
(101.2°F) tympanic, or = 39°C (102.2°F) rectal (observed by a health care
provider)
- WBC count = 10,000 cells/mm3 or < 4000 cells/mm3
- > 10% immature neutrophils
? Post-traumatic wound (including penetrating trauma [needle, nail, knife])
characterized by all of the following within 24 hours:
? Purulent drainage from a wound with surrounding erythema extending at least 5
cm from the peripheral margin of the wound
? At least 1 of the following systemic signs of infection:
- Lymph node tenderness and increase in volume or palpable proximal to the
primary ABSSSI
- Fever, defined as body temperature = 38°C (100.4°F) oral, = 38.5°C
(101.2°F) tympanic, or = 39°C (102.2°F) recta

Exclusion Criteria

1.Uncomplicated skin and skin structure infections (SSSIs) such as furuncles, minor abscesses (area of suppuration not surrounded by cellulitis/erysipelas), impetiginous lesions, superficial or limited cellulitis/erysipelas, and minor wound infections (eg, stitch abscesses)
2. Infections associated with, or in close proximity to, a prosthetic device
3. Severe sepsis or septic shock
4. Known bacteremia at time of screening
5. ABSSSI due to or associated with any of the following:
? Suspected or documented gram-negative pathogens in patients with
cellulitis/erysipelas or major cutaneous abscess that require an antibiotic with specific
gram-negative coverage. Patients with wound infections where gram-negative
adjunctive therapy is warranted may be enrolled if they meet the other eligibility
criteria
? Diabetic foot infection, gangrene, or perianal abscess
? Concomitant infection at another site not including a secondary ABSSSI lesion (eg,
septic arthritis, endocarditis, osteomyelitis)
? Infected burns
? Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease
(arterial or venous)
? Any evolving necrotizing process (ie, necrotizing fasciitis)
? Infected human or animal bites
? Infections at vascular catheter sites or involving thrombophlebitis
? Incisional SSI with any of the following characteristics:
? Follows clean-contaminated surgery (urgent or emergency case that is otherwise
clean, elective opening of respiratory, gastrointestinal, biliary, or genitourinary
tract with minimal spillage [eg, appendectomy] not encountering infected urine or
bile; minor technique break)
? Follows contaminated surgery (nonpurulent inflammation; gross spillage from
gastrointestinal tract; entry into biliary or genitourinary tract in the presence of
infected bile or urine; major break in technique)
? Follows dirty surgery (purulent inflammation [eg, abscess]; preoperative
perforation of respiratory, gastrointestinal, biliary, or genitourinary tract)
? Extends into the fascial or muscle layers, organs, or spaces
6. Use of antibiotics as follows:
? Systemic antibiotic with gram-positive cocci activity for the treatment of any
infection within 96 hours before Dose 1 of study drug
? Patients who failed prior therapy for the primary infection site are also excluded
from enrollment
? Topical antibiotic on the primary lesion except for antibiotic/antiseptic-coated
dressing applied to the clean postsurgical wound
7. Administration of linezolid within 30 days before Dose 1
8. Recent history of opportunistic infections where the underlying cause of these infections is still active (eg, leukemia, transplant, acquired immunodeficiency syndrome [AIDS])
9. Receiving chronic systemic immunosuppressive therapy such as prednisone doses = 20 mg per day for = 3 of the last 12 months OR therapies that in the Investigator’s judgment could predispose to opportunistic infections
10. Receiving treatment for active tuberculosis
11. Last known CD4 count < 200 cells/mm3 in patients with AIDS
12. Current or anticipated neutropenia with ANC < 1000 cells/mm3
13. Severe renal disease defined as creatinine clearance (CrCl) < 30 mL/min estimated by the Cockcroft-Gault formula OR requirement for peritoneal dialysis, plasmapheresis, hemodialysis, venovenous dialysis, or other forms of renal filtration
14. ALT or AST = 5 upper limit of normal OR moderate to severe hepatic disease with Child-Pugh score =7 defined by the following:
? Presence of ascites upon examin