Characterization of Neurologic and Ophthalmologic Safety of Oral Administration of Tedizolid for Up to 21 Days in Healthy Volunteers

摘要

Background: Antibacterials that inhibit protein synthesis may be associated with mitochondrial toxicity, manifested as serious optic or peripheral neuropathy or myelosuppression. Tedizolid is a novel oxazolidinone antibacterial that may have reduced the potential for mitochondrial toxicity. Study Question: Based on the results of 2 studies (NCT01623401 and NCT00671814) conducted early in the tedizolid development program, what is the potential for drug-induced optic and peripheral neuropathies with tedizolid treatment? Methods: Two phase-1 studies were conducted in healthy volunteers. The first was an open-label study in which subjects received 200 mg of oral tedizolid phosphate once daily for 10 days. The second was a double-blind, placebo- and active-controlled, dose-escalating (multiple-administration) study in which subjects received 200, 300, or 400 mg of oral tedizolid phosphate once daily or 600 mg of oral linezolid twice daily or oral placebo for 21 days. Overall safety and tolerability were asses ed, and extensive ophthalmologic and neurologic assessments were performed in both studies. Results: In these 2 studies in healthy subjects, tedizolid administered for up to 21 days was not associated with drug-related ophthalmologic or neurologic adverse events. Incidences of adverse events involving the eye or the nervous system were generally low, and no clinically meaningful changes in ophthalmologic or neurologic test results were recorded during either study. Conclusions: Using an extensive battery of ophthalmologic tests and detailed neurologic clinical examination, there was no evidence of clinical or subclinical neurologic or ophthalmologic changes suggestive of peripheral or optic neuropathy in healthy volunteers who received therapeutic and supratherapeutic doses of oral tedizolid for periods of up to 21 days.