TY - JOUR
T1 - Early Bactericidal Activity of Delpazolid (LCB01-0371) in Patients with Pulmonary Tuberculosis
AU - Kim, Ju Sang
AU - Kim, Yong Hyun
AU - Lee, Sang Haak
AU - Kim, Yee Hyung
AU - Kim, Jin Woo
AU - Kang, Ji Young
AU - Kim, Sung Kyoung
AU - Kim, Seung Joon
AU - Kang, Yun Seong
AU - Kim, Tae Hyung
AU - Mok, Jeongha
AU - Byun, Min Kwang
AU - Park, Hye Jung
AU - Joh, Joon Sung
AU - Park, Yong Bum
AU - Lim, Hyeong Seok
AU - Choi, Hongjo
AU - Lee, Seung Heon
AU - Kim, Hyejin
AU - Yang, Jeongseong
AU - Kim, Hyunji
AU - Shen, Xianlin
AU - Alsultan, Abdullah
AU - Cho, In Sook
AU - Geiter, Lawrence
AU - Shim, Tae Sun
N1 - Publisher Copyright:
© 2022 Kim et al.
PY - 2022/2
Y1 - 2022/2
N2 - Delpazolid, an oxazolidinone, has been studied in non-clinical studies of efficacy and toxicity and Phase 1 clinical studies. Delpazolid has in vitro activity against Gram-positive bacteria, including Mycobacterium tuberculosis. This study evaluated the bactericidal activity, safety, and pharmacokinetics of delpazolid in patients with pulmonary tuberculosis (TB). Seventy-nine subjects, aged 19 to 75 years with newly diagnosed smear-positive TB with no prior treatment for the current episode and no confirmed resistance to rifampin or isoniazid, were randomized to receive delpazolid 800 mg once a day (QD), 400 mg twice a day (BID), 800 mg BID or 1,200 mg QD or an active control of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) or linezolid 600 mg BID. The primary endpoint was the average daily reduction in log transformed bacterial load, assessed on 7H11 solid-media culture, from days 0 to 14. The average daily decline in log-CFU was 0.044 6 0.016, 0.053 6 0.017, 0.043 6 0.016, and 0.019 6 0.017, for the delpazolid 800 mg QD, 400 mg BID, 800 mg BID, and the 1,200 mg QD groups, respectively. The average daily decline in log-CFU was 0.192 6 0.028 for the HRZE group and 0.154 6 0.023 for the linezolid 600 mg BID group. Three serious adverse events (SAE) were reported, one each in the delpazolid 400 mg BID group (death due to worsening of TB at day 2), the HRZE group (hospitalization due to pleural effusion) and the linezolid group (hyperkalemia); none of the SAEs were assessed as related to study drugs.
AB - Delpazolid, an oxazolidinone, has been studied in non-clinical studies of efficacy and toxicity and Phase 1 clinical studies. Delpazolid has in vitro activity against Gram-positive bacteria, including Mycobacterium tuberculosis. This study evaluated the bactericidal activity, safety, and pharmacokinetics of delpazolid in patients with pulmonary tuberculosis (TB). Seventy-nine subjects, aged 19 to 75 years with newly diagnosed smear-positive TB with no prior treatment for the current episode and no confirmed resistance to rifampin or isoniazid, were randomized to receive delpazolid 800 mg once a day (QD), 400 mg twice a day (BID), 800 mg BID or 1,200 mg QD or an active control of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) or linezolid 600 mg BID. The primary endpoint was the average daily reduction in log transformed bacterial load, assessed on 7H11 solid-media culture, from days 0 to 14. The average daily decline in log-CFU was 0.044 6 0.016, 0.053 6 0.017, 0.043 6 0.016, and 0.019 6 0.017, for the delpazolid 800 mg QD, 400 mg BID, 800 mg BID, and the 1,200 mg QD groups, respectively. The average daily decline in log-CFU was 0.192 6 0.028 for the HRZE group and 0.154 6 0.023 for the linezolid 600 mg BID group. Three serious adverse events (SAE) were reported, one each in the delpazolid 400 mg BID group (death due to worsening of TB at day 2), the HRZE group (hospitalization due to pleural effusion) and the linezolid group (hyperkalemia); none of the SAEs were assessed as related to study drugs.
KW - Early bactericidal activity
KW - Experimental therapeutics
KW - Mycobacterium tuberculosis
KW - Oxazolidinones
UR - http://www.scopus.com/inward/record.url?scp=85124634127&partnerID=8YFLogxK
U2 - 10.1128/aac.01684-21
DO - 10.1128/aac.01684-21
M3 - Article
C2 - 34871098
AN - SCOPUS:85124634127
SN - 0066-4804
VL - 66
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 2
M1 - e01684-21
ER -