Zabofloxacin versus moxifloxacin in patients with COPD exacerbation: a multicenter, double-blind, double-dummy, randomized, controlled, Phase III, non-inferiority trial

Abstract

Chin Kook Rhee,1 Jung Hyun Chang,2 Eu gene Choi,3 Hyun kuk Kim,4 Yong-Soo Kwon,5 Sun Young Kyung,6 Ji-Hyun Lee,7 Myung Jae Park,8 Kwang Ha Yoo,9 Yeon Mok Oh10 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary’s Hospital, College of Medicine, The Catholic University of Korea, 2Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, School of Medicine, Ewha Womans University Medical Center, Seoul, 3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Daejeon Hankook Hospital, Daejeon, 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, 5Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Chonnam National University Hospital, Gwangju, 6Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, 7Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, CHA Bundang Medical Center of CHA University, Seongnam, 8Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, KyungHee University Hospital, Seoul, 9Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University School of Medicine, 10Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Abstract: A new quinolone, zabofloxacin, has now been developed; hence, a non-inferiority trial is needed to compare this new compound with another widely used quinolone to examine its efficacy and safety for the treatment of chronic obstructive pulmonary disease (COPD) exacerbations. This was a prospective, multicenter, double-blind, double-dummy, randomized, controlled, parallel-group, Phase III, non-inferiority clinical trial designed to compare oral zabofloxacin (367 mg once daily for 5 days) with moxifloxacin (400 mg once daily for 7 days) for the treatment of patients with COPD exacerbation. In all, 345 COPD patients with a moderate COPD exacerbation were enrolled in the study via the outpatient clinics at 31 university hospitals. Clinical per protocol analysis revealed that the clinical cure rate for zabofloxacin was 86.7% and that for moxifloxacin was 86.3% (the rate difference, 0.4%; 95% confidence interval, –7.7%–8.6%). Intention-to-treat analysis revealed clinical cure rates of 77.1% and 77.3% (difference, –0.2%; 95% confidence interval, –9.0%–8.8%), respectively. These results confirm that zabofloxacin is not inferior to moxifloxacin. The favorable microbiological response rate for zabofloxacin was 67.4% and that for moxifloxacin was 79.5% (P=0.22). Patients in the zabofloxacin group showed better patient-oriented outcomes, as measured by EXAcerbations of Chronic Pulmonary Disease Tool-Patient-Reported Outcome and the COPD assessment test scores, than patients in the moxifloxacin group. Adverse drug reactions related to zabofloxacin occurred in 9.7% of cases and those related to moxifloxacin occurred in 9.6% of cases (P=0.97). The dropout rate due to adverse events was 0% (0/175) in the zabofloxacin group and 1.8% (3/167) in the moxifloxacin group (P=0.12). Oral zabofloxacin (367 mg once daily for 5 days) was not inferior to oral moxifloxacin (400 mg once daily for 7 days) for the treatment of patients with COPD exacerbation. Keywords: chronic obstructive pulmonary disease, exacerbation, zabofloxacin, quinolone, EXACT-PRO, CAT