Effects of tedizolid phosphate and linezolid on platelet counts in a phase 3 ABSSSI study

Purpose: Tedizolid phosphate is a novel oxazolidinone prodrug antibiotic of the active moiety tedizolid, being developed for the treatment of acute bacterial skin and skin structure infections (ABSSSI). The only oxazolidinone currently on the market is linezolid (Zyvox) which has been associated with thromobocytopenia. Platelet counts in subjects enrolled in a phase 3 ABSSSI study comparing 6 days of oral tedizolid phosphate 200 mg qd (followed by 4 days of placebo) with 10 days of oral linezolid 600 mg bid were reviewed.

Methods: A total of 666 adult subjects with ABSSSI were randomized to tedizolid phosphate or linezolid treatment and received at least one dose of study drug. Platelet counts were reviewed for worst post-baseline values and values at Study Days 11-13.

Results: Number of subjects receiving tedizolid phosphate and linezolid with post-baseline platelet counts below the lower limit of normal (LLN) or were substantially abnormal (<75% of LLN) are presented in the table below.  

Subjects groups	Tedizolid phosphate n (%)	Linezolid n (%)	p-value
Subjects with any baseline platelet count and the worst (lowest) post-baseline value      Below LLN      Substantially abnormal	N = 304 28 (9.2) 7 (2.3)	N = 308 46 (14.9) 15 (4.9)	0.035 0.127
Excluding subjects with an abnormal or missing baseline platelet count, values at Study Days 11-13      Below LLN      Substantially abnormal	N = 259 8 (3.1) 1 (0.4)	N = 247 19 (7.7) 7 (2.8)	0.0282 0.0337
Including subjects with an abnormal baseline value and excluding subjects with a missing baseline platelet count, values at Study Days 11-13      Below LLN      Substantially abnormal	N = 268 9 (3.4) 2 (0.7)	N = 266 30 (11.3) 12 (4.5)	0.0004 0.0065

Conclusion: Subjects receiving tedizolid phosphate in this phase 3 ABSSSI trial had lower rates of abnormal platelet counts compared with linezolid, which in many cases were statistically significant.