Safety, tolerability and pharmacokinetics of 21 day multiple oral administration of a new oxazolidinone antibiotic, LCB01-0371, in healthy male subjects

• Published in: Journal of antimicrobial chemotherapy Vol. 73; no. 1; pp. 183 - 190
• Main Authors: Choi, Yewon, Lee, Sang Won, Kim, Anhye, Jang, Kyungho, Nam, Heesook, Cho, Young Lag, Yu, Kyung-Sang, Jang, In-Jin, Chung, Jae-Yong
• Format: Journal Article
• Language: English
• Published: England 01.01.2018
• Subjects: Administration, Oral; Adult; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - pharmacology; Area Under Curve; Double-Blind Method; Erythrocyte Count; Gram-Positive Bacteria - drug effects; Healthy Volunteers; Humans; Male; Middle Aged; Oxazolidinones - administration & dosage; Oxazolidinones - adverse effects; Oxazolidinones - pharmacokinetics; Oxazolidinones - pharmacology; Young Adult
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/dkx367

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. The safety, tolerability and pharmacokinetics (PK) of 21 day multiple oral administrations of LCB01-0371 in healthy male subjects (clinicaltrials.gov: NCT02540460) were investigated. 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. 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 × 106/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. 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.