Phase III study of garenoxacin in patients with secondary infection of chronic respiratory diseases

The efficacy and safety of garenoxacin mesilate hydrate(GRNX), new oral des-fluoroquinolone antimicrobial, were investigated in patients with secondary infection occurred on chronic respiratory disorders. Patients were treated with GRNX 400 mg once daily for 10 days. Plasma concentration of GRNX in each patient was determined and the obtained clinical results were analysed based on pharmacokinetics(PK) and pharmacokinetics/pharmacodynamics(PK/PD) parameters. Clinical efficacy rates were 87.8% (108/123) at the end of treatment and 83.7% (103/123) at the 7th day of post-treatment. Bacteriological eradication rates were 89.6% (60/67) and 85.1% (57/67) at the above time points. Eradication rates of causative organisms were 100% (13/13) in Streptococcus pneumoniae, 7/8 in Staphylococcus aureus, 100% (28/28) in Haemophilus influenzae and 8/8 in Moraxella (Branhamella) catarrhalis at the end of treatment. All penicillin-resistant S. pneumoniae(PRSP) including penicillin-intermediate resistant S. pneumoniae(PISP) were eradicated. Drug-related adverse events were observed in 19 patients (26 events), the incidence rate was 14.0% (19/136). Gastrointestinal disorders including 4 cases of diarrhea (2.9%), 3 of loose stool (2.2%) and 3 of vomiting (2.2%) were frequently observed. Laboratory abnormalities were observed in 26 patients (19.3%). Frequent abnormalities were 14 cases of AST elevation (10.4%), 13 of ALT elevation (9.6%) and 5 of serum amylase elevation (3.8%). No relationship was observed between PK parameters (AUC_0-24 and Cmax) and incidence of adverse events. 90.9% of patient in this study exceeded the target value of fAUC_0-24/MIC > 50. Clinical efficacy at the 7th day of post-treatment was 91.7% (55/60) in those cases whose target value was more than 50, but it was only 3/6 in those whose target value was less than 50. Similar results were obtained in studies in US and EU. From aboves, it indicates that GRNX is a beneficial antimicrobial agent for secondary infection of chronic respiratory diseases.