Safety, tolerability and pharmacokinetics of 21 day multiple oral administration of a new oxazolidinone antibiotic, LCB01-0371, in healthy male subjects. (23rd October 2017)

• Record Type: Journal Article
• Authors: Choi, Yewon; Lee, Sang Won; Kim, Anhye; Jang, Kyungho; Nam, Heesook; Cho, Young Lag; Yu, Kyung-Sang; Jang, In-Jin; Chung, Jae-Yong
• Is Part Of: Journal of antimicrobial chemotherapy. Volume 73:Number 1(2018)
• Page Start: 183
• Page End: 190
• Publication Date: 2017-10-23
• Subjects: Anti-infective agents -- Periodicals; Chemotherapy -- Periodicals; 615.58
• DOI: 10.1093/jac/dkx367
• Languages: English
• ISSNs: 0305-7453

Abstract

Abstract: Background: LCB01-0371 is a new oxazolidinone antibiotic, which targets most Gram-positive organisms. High rates of adverse reactions including myelosuppression have been reported for existing oxazolidinones, limiting their long-term use. Objectives: The safety, tolerability and pharmacokinetics (PK) of 21 day multiple oral administrations of LCB01-0371 in healthy male subjects (clinicaltrials.gov: NCT02540460) were investigated. Methods: In this randomized, double-blind, placebo-controlled study, subjects received 800 mg of LCB01-0371 once or twice daily or 1200 mg of LCB01-0371 twice-daily for 21 days in a fasting state. Safety and tolerability profiles including laboratory tests were evaluated during the study and on a post-study visit and the results were analysed using repeated-measures analysis of variance (RM-ANOVA). Serial blood samples for PK analysis were collected up to 12 h after dosing on day 21. Results: A total of 40 subjects were enrolled and 34 subjects completed the study. Two subjects dropped out according to stopping rules. In the 1200 mg twice-daily dose group, the absolute value of red blood cell count, haematocrit and haemoglobin decreased by 500 × 10 6 /L (6.5%), 4.5% (6.8%) and 1.6 g/dL (6.9%), respectively, after 21 day administrations of LCB01-0371. However, mean relative changes from baseline of all haematology values were not significantly different among doses, including placebo (all, P < 0.05). PK profiles of LCB01-0371 in the dose range of 800 mg once daily to 1200 mg twice daily were consistent with previous studies. Conclusions: LCB01-0371 is well tolerated in healthy male subjects with comparable haematology profiles to placebo, after multiple doses of up to 1200 mg twice daily for 21 days.