Efficacy and Safety of Tedizolid Phosphate versus Linezolid in a Randomized Phase 3 Trial in Patients with Acute Bacterial Skin and Skin Structure Infection

Abstract

Tedizolid phosphate is approved for the treatment of acute bacterial skin and skin structure infection (ABSSSI) caused by Gram-positive bacteria in the United States, Europe, and other countries. In this multicenter, double-blind, phase 3 study, 598 adult ABSSSI patients in China, Taiwan, the Philippines, and the United States were randomized to receive 200 mg of tedizolid, intravenously (i.v.)/orally (p.o.), once daily for 6 days or 600 mg of linezolid, i.v./p.o. twice daily for 10 days. The primary endpoint was early clinical response rate at 48 to 72 h. Secondary endpoints included programmatic and investigator-assessed outcomes at end-of-therapy (EOT) and posttherapy evaluation (PTE) visits. Safety was also evaluated. In the intent-to-treat (ITT) population, 75.3% of tedizolid-treated patients and 79.9% of linezolid-treated patients were early responders (treatment difference, -4.6%; 95% confidence interval [CI], -11.2, 2.2). After exclusion of patients who never received the study drug (tedizolid, n = 8; linezolid, n = 1; modified ITT), comparable early response rates were observed (tedizolid, 77.4%; linezolid, 80.1%; treatment difference, -2.7%; 95% CI, -9.4, 3.9). Secondary endpoints showed high and similar clinical success rates in the ITT and clinically evaluable (CE) populations at EOT and PTE visits (e.g., CE-PTE for tedizolid, 90.4%; for linezolid, 93.5%). Both drugs were well tolerated, and no death occurred. Eight patients experienced phlebitis with tedizolid while none did with linezolid; hence, drug-related treatment-emergent adverse events were reported in a slightly higher proportion in the tedizolid (20.9%) arm than in the linezolid arm (15.8%). The study demonstrated that tedizolid in a primarily Asian population was an efficacious and well-tolerated treatment option for ABSSSI patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02066402.).

Keywords: Asian patients; Chinese patients; acute bacterial skin and skin structure infection; linezolid; methicillin-resistant Staphylococcus aureus; oxazolidinone; randomized controlled phase 3 trial; tedizolid phosphate.

Copyright © 2019 Lv et al.

Figures

FIG 1

Patient flow through the study. *, withdrew consent (n = 7) or noncompliance with study drug (n = 1); **, lost to follow-up (n = 1); †, patients could have been excluded for more than one reason; ‡, included all patients who were eligible for inclusion in the CE-PTE analysis set with at least one Gram-positive pathogen at baseline; ^, blood culture was negative at screening but positive at a later time point, and the collection of a blood sample was clinically indicated for culture.

FIG 2

Per-patient overall favorable microbiological response at posttherapy evaluation visit (PTE). CI, confidence interval; ME, microbiological evaluable; MITT, microbiological intent to treat. A favorable response was equivalent to “presumed eradication” for the different baseline infection types.