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

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: CAT; EXACT-PRO; chronic obstructive pulmonary disease; exacerbation; quinolone; zabofloxacin.

Figure 1

Disposition of patients during study. Notes: ¹Clinical ITT set: This population consisted of all randomized subjects who received at least one dose of the investigational product. ²Clinical PP set: This population consisted of all randomized subjects who met the study inclusion and/or exclusion criteria, who received an adequate course of therapy, for whom sufficient information was available to determine the subject’s outcome, and who had no confounding factors that interfered with the assessment of the outcome. ³Microbiological PP set: This population consisted of a subset of the clinical PP subjects who had a baseline pathogen identified. Abbreviations: ZBO, zabofloxacin; MOX, moxifloxacin; ITT, intention-to-treat; PP, per protocol.

Figure 2

Clinical per protocol analysis of changes in the EXACT-PRO and CAT scores. Notes: The EXACT-PRO (A) and CAT scores (B) decreased significantly compared with those on D1 (*P<0.05, **P<0.01 vs D1) in both the zabofloxacin and moxifloxacin groups. The decline in the EXACT-PRO (C) scores on D6 and D7 and the decline in the CAT scores (D) on D5, D6, and D7 were significantly greater in the zabofloxacin than in the moxifloxacin group (*P<0.05 and **P<0.01 between the zabofloxacin and moxifloxacin groups). Abbreviations: EXACT-PRO, EXAcerbations of Chronic Pulmonary Disease Tool-Patient-Reported Outcome; CAT, chronic obstructive pulmonary disease assessment test; D, day.

Figure 3

Clinical intention-to-treat analysis of the changes of EXACT-PRO and CAT scores. Notes: The EXACT-PRO (A) and CAT scores (B) decreased significantly compared with those on D1 (*P<0.05, **P<0.01 vs D1) in both the zabofloxacin and moxifloxacin groups. The decline in the EXACT-PRO (C) scores on D6 and D7 and the decline in the CAT scores (D) on D5, D6, D7, and D36 were significantly greater in the zabofloxacin than in the moxifloxacin group (*P<0.05 and **P<0.01 between the zabofloxacin and moxifloxacin groups). Abbreviations: EXACT-PRO, EXAcerbations of Chronic Pulmonary Disease Tool-Patient-Reported Outcome; CAT, chronic obstructive pulmonary disease assessment test; D, day.