TY - JOUR
T1 - A phase 2 randomized, double-blind, dose-ranging study evaluating the safety, tolerability, population pharmacokinetics, and efficacy of oral torezolid phosphate in patients with complicated skin and skin structure infections
AU - Prokocimer, P
AU - Bien, P
AU - Surber, J
AU - Mehra, P
AU - DeAnda, C
AU - Bulitta, Jurgen
AU - Corey, G R
PY - 2011
Y1 - 2011
N2 - Torezolid (TR-700) is the active moiety of the prodrug torezolid phosphate (TP, TR-701), a
second generation oxazolidinone with 4- to 16-fold greater potency than linezolid against gram
positive species including methicillin-resistant Staphylococcus aureus (MRSA). A double-blind
Phase 2 study evaluated three levels (200, 300, or 400mg) of oral, once daily TP over 5-7 days
for complicated skin and skin structure infections (cSSSI). Patients 18-75 years with cSSSI
suspected or confirmed gram positive pathogens were randomized 1:1:1. Of 188 treated patients,
76.6 had abscesses, 17.6 had extensive cellulitis, and 5.9 had wound infections. S. aureus,
the most common pathogen, was isolated in 90.3 of patients (139/154) with a baseline
pathogen; 80.6 were MRSA. Cure rates in clinically evaluable patients were 98.2 at 200mg,
94.4 at 300mg, and 94.4 at 400mg. Cure rates were consistent across diagnoses, regardless
of lesion size or the presence of systemic signs of infection. Clinical cure rates in patients with
S. aureus isolated at baseline was 96.6 overall and 96.8 for MRSA. TP was safe and well
tolerated at all dose levels. No patients discontinued treatment due to an adverse event. Three-
stage hierarchical population pharmacokinetic modeling yielded a geometric mean clearance of
8.28L/h (between patient variability 32.3 ), volume of central compartment 71.4L (24.0 ), and
of peripheral compartment 27.9L (35.7 ). Results of this study show a high degree of efficacy
at all three dose levels without significant differences in the safety profile, and support the
continued evaluation of TP for the treatment of cSSSI in Phase 3 trials.
AB - Torezolid (TR-700) is the active moiety of the prodrug torezolid phosphate (TP, TR-701), a
second generation oxazolidinone with 4- to 16-fold greater potency than linezolid against gram
positive species including methicillin-resistant Staphylococcus aureus (MRSA). A double-blind
Phase 2 study evaluated three levels (200, 300, or 400mg) of oral, once daily TP over 5-7 days
for complicated skin and skin structure infections (cSSSI). Patients 18-75 years with cSSSI
suspected or confirmed gram positive pathogens were randomized 1:1:1. Of 188 treated patients,
76.6 had abscesses, 17.6 had extensive cellulitis, and 5.9 had wound infections. S. aureus,
the most common pathogen, was isolated in 90.3 of patients (139/154) with a baseline
pathogen; 80.6 were MRSA. Cure rates in clinically evaluable patients were 98.2 at 200mg,
94.4 at 300mg, and 94.4 at 400mg. Cure rates were consistent across diagnoses, regardless
of lesion size or the presence of systemic signs of infection. Clinical cure rates in patients with
S. aureus isolated at baseline was 96.6 overall and 96.8 for MRSA. TP was safe and well
tolerated at all dose levels. No patients discontinued treatment due to an adverse event. Three-
stage hierarchical population pharmacokinetic modeling yielded a geometric mean clearance of
8.28L/h (between patient variability 32.3 ), volume of central compartment 71.4L (24.0 ), and
of peripheral compartment 27.9L (35.7 ). Results of this study show a high degree of efficacy
at all three dose levels without significant differences in the safety profile, and support the
continued evaluation of TP for the treatment of cSSSI in Phase 3 trials.
U2 - 10.1128/AAC.00076-10
DO - 10.1128/AAC.00076-10
M3 - Article
SN - 0066-4804
VL - 55
SP - 583
EP - 592
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 2
ER -