Study of oral Garenoxacin in Japanese patients with secondary infection of chronic respiratory diseases and penetration into sputum

Abstract number: 1733_1513

Kobayashi H., Watanabe A., Fujimaki K.

Objectives: Garenoxacin (GRN), a des-F(6)-quinolone, has strong activity against respiratory tract infection pathogens including multi-drug resistant S. pneumoniae (MDRSP). The objective of this study was to evaluate the clinical response of GRN against secondary infection of chronic respiratory disease namely acute exacerbation of chronic bronchitis (AECB). Penetration into sputum was also examined.

Methods: An open-label study was conducted to evaluate clinical response and microbiological response to treatment with oral GRN 400 mg QD for 10 days in adults with secondary infection of chronic respiratory disease in Japan. The study followed another GRN AECB study conducted in the US and Europe. The clinical efficacy of GRN was assessed upon completion of treatment and 7 days post-treatment. Safety was assessed up to 7 days post-treatment. The drug concentration of GRN in sputum after administration of GRN 400 mg was also measured.

Results: 136 subjects were enrolled in this study. The efficacy rate of GRN 7 days post-treatment in subjects with secondary infection of chronic bronchitis was 91.3%. A similar efficacy rate (94.3%) was observed in the AECB study conducted in the US and Europe. The bacterial eradication rate of GRN against Gram-positive pathogens was 90.9%. Bacterial eradication rates against PRSP, PISP and BLNAR were 100%. Drug related adverse events (AEs) were observed in 14.0% of the subjects; no serious AEs were found among them. The main AEs were gastrointestinal disorders, and all events were mild to moderate. The main laboratory abnormalities were ALT increase and AST increase. Similar AEs were observed in the US/European study. The drug concentration of GRN in sputum 3 hours after administration of GRN 400 mg was 3.50 ± 1.17 micro g/g (fluid to plasma ratio: 0.536 ± 0.273). This was regarded as efficient penetration well over the susceptibility level of major pathogens causing respiratory tract infection.

Conclusions: A 10-day course of oral GRN 400 mg QD showed good efficacy in the treatment of secondary infection of chronic respiratory disease. Good penetration into sputum was also confirmed.