Efficacy and safety of tedizolid phosphate for 6 days vs. linezolid for 10 days in a phase 3 study in patients with ABSSSI using the new FDA primary outcome measure

Purpose: The FDA is using a new primary outcome measure for acute bacterial skin and skin structure infections (ABSSSI) of cessation of spread and absence of fever at an early time point at 48-72 hours after the first dose of study medication. 

Methods: This was a randomized, double-blind, multicenter Phase 3 study of oral tedizolid phosphate 200 mg QD for 6 days versus oral linezolid 600 mg every 12 hours for 10 days for the treatment of ABSSSIs in adults.  The primary objective was to determine the non-inferiority in the early clinical response rate of 6‑day oral tedizolid phosphate compared with that of 10-day oral linezolid treatment at the 48-72 Hour Visit in the ITT analysis set in patients with ABSSSI. Patients were programmatically defined as a responder at the 48-72 Hour Visit if there was documented cessation of spread of the primary ABSSSI and an absence of fever.

Results: A total of 667 patients were randomized. The primary ABSSSI type enrolled was cellulitis (41%) followed by major cutaneous abscesses (30%) and infected wounds (29%).  Median measurements of surface area of lesion were comparable in both treatment groups.  The primary outcome results are listed in table below.  The primary reason for indeterminate was out of window or missing temperature measurements.

Response	Tedizolid phosphate (N=332) n (%)	Linezolid (N=335) n (%)
Responder	264 (79.5)	266 (79.4)
Non-responder or indeterminate Non-responder Indeterminate	68 (20.5) 27 (8.1) 41 (12.3)	69 (20.6) 35 (10.4) 34 (10.1)

Treatment emergent adverse events were balanced overall between the two treatment groups.  However there was a statistically significantly higher incidence of GI-related adverse events with linezolid.

Conclusion: The results of this study demonstrated that tedizolid phosphate QD for 6 days achieved its primary endpoint of non-inferiority versus linezolid Q12H for 10 days.