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:

• chronic obstructive pulmonary disease
• exacerbation
• zabofloxacin
• quinolone
• EXACT-PRO
• CAT

Acknowledgments

This study was supported by Dongwha Pharm. Co., Ltd., Seoul, Korea.

The members (other than authors) of this study are as follows: Sook Young Lee (Seoul St. Mary’s Hospital, Seoul, Korea), Sung Hwan Jung, Jeong Woong Park (Gachon University Gil Medical Center, Incheon, Korea), Ju Sang Kim, Joong Hyun Ahn, Ah Young Shin, Hwa Young Lee (Incheon St. Mary’s Hospital, Incheon, Korea), Woo Jin Kim, Yoonki Hong (Kangwon National University Hospital, Chencheon, Korea), Jong Deog Lee, Yi Young Jung (Gyeongsang National University, Jinju, Korea), Hee Joung Kim (Konkuk University Medical Center, Seoul, Korea), Chi Young Jung, Young June Jeon (Keimyung University Dongsan Medical Center, Daegu, Korea), Sang Yeub Lee, Kwang Ho In, Eun Joo Lee (Korea University Anam Hospital, Seoul, Korea), Sang-Do Lee, Sei Won Lee, Jae Seung Lee (Asan Medical Center, Seoul, Korea), Hun Gyu Hwang, Gune-Il Lim, Myung Shin Kim (Soonchunhyang University Hospital Gumi, Gumi, Korea), Ju Ock Na, Yong Hoon Kim, Jae Sung Choi, Ho Sung Lee (Soonchunhyang University Cheonan Hospital, Cheonan, Korea), Seung Soo Sheen, Keu Sung Lee (Ajou University Hospital, Suwon, Korea), Seung Won Ra, Kwang Won Seo, Yangjin Jegal, Jong-Joon Ahn (Ulsan University Hospital, Ulsan, Korea), Won Yeon Lee, Myoung Kyu Lee, Suk Joong Yong, Kye Chul Shin (Yonsei University Wonju Severance Christian Hospital, Wonju, Korea), Jin Hwa Lee, Yon Ju Ryu, Seok Jeong Lee (Ewha Womans University Mokdong Hospital, Seoul, Korea), Hang Jea Jang (Haeundae Paik Hospital, Busan, Korea), Yong Chul Lee, So Ri Kim, Seung Yong Park, Chi Ryang Chung (Chonbuk National University Hospital, Jeonju, Korea), Sung Soo Jung, Ju Ock Kim, Jeong Eun Lee (Chungnam National University Hospital, Daejeon, Korea), Kang Hyeon Choe, Ki Man Lee, Jin Young An (Chungbuk National University Hospital, Cheongju, Korea), Yong Bum Park, Changhwan Kim, Jae Young Lee, Eun Kyung Mo (Hallym University Kangdong Sacred Heart Hospital, Seoul, Korea), Seung Hun Jang, Ki Suck Jung (Hallym University Sacred Heart Hospital, Anyang, Korea), Tae-Hyung Kim, Ji-Young Moon (Hanyang University Guri Hospital, Guri, Korea), Hye Sook Choi (Dongguk University Gyeongju Hospital, Gyeongju, Korea), Young Sam Kim (Severance Hospital, Seoul, Korea), Kyeong-Cheol Shin (Yeungnam University Medical Center, Daegu, Korea), Sung Ho Yoon (Chosun University Hospital, Gwangju, Korea).

We express our special thanks to Cheol Hee Lim and Sun Hea Lee, Dongwha Pharm. Co., Ltd., Seoul, Korea.

Disclosure

CK Rhee received consulting/lecture fees from MSD Korea, AstraZeneca Korea, Novartis Korea, GSK Korea, Takeda Korea, Mundipharma Korea, Sandoz Korea and Boehringer-Ingelheim Korea. YM Oh received honoraria/consulting fees from DongWha, MSD Korea, AstraZeneca Korea, GlaxoSmithKline Korea, Novartis, and Boehringer-Ingelheim Korea. The other authors report no other conflicts of interest in this work.