Meeting the Unmet Need in the Management of MDR Gram-Positive Infections with Oral Bactericidal Agent Levonadifloxacin

Table 4

Summary of clinical studies with levonadifloxacin and alalevonadifloxacin.

Aim of the Study	Dose	No. of subjects	Study outcome
Crossover food-effect and absolute bioavailability study of alalevonadifloxacin [65]	800 mg (IV) and 1000 mg (oral)	12	Alalevonadifloxacin could be delivered regardless of fed or fasted state. Alalevonadifloxacin had concentration-time profile similar to that of levonadifloxacin. These findings suggest that switching from an intravenous to an oral formulation of levonadifloxacin is effective for inpatients
Determine the supratherapeutic dose of alalevonadifloxacin and assess its effect on cardiac repolarization as shown by analysis of the QT interval [66]	Part 1: Single dose of 1800 mg, 2200 mg, 2600 mg, and 3000 mg; Part 2: Single dose of 2600 mg, moxifloxacin 400 mg, and placebo matched to moxifloxacin	Part 1: 32 (24 alalevonadifloxacin  + 8 placebo); Part 2: 48	Supratherapeutic dose of alalevonadifloxacin is not likely to elicit clinically significant ECG effects and thus can provide a viable alternative to QT prolonging antibiotics
Evaluate the effect of hepatic impairment on the pharmacokinetics of levonadifloxacin and its sulfate metabolite after single oral dose administration of alalevonadifloxacin [50]	1000 mg	48	There were no significant differences () in the PK parameters of levonadifloxacin or its sulfate metabolite in mild or moderate hepatic impaired groups compared to normal matched control groups. Levonadifloxacin and alalevonadifloxacin could be safely administered to patients with hepatic impairment in order to obtain a therapeutically suitable PK profile
Determine and compare plasma, ELF, and AM concentrations of levonadifloxacin after oral administration of alalevonadifloxacin [61]	1000 mg BID x 5 days	31	The penetration ratios for ELF and AM to plasma concentration for levonadifloxacin were 7.66 and 1.58, respectively, supporting its use for lower respiratory tract infections
Comparative study of levonadifloxacin (IV and oral) with linezolid (IV and oral) in ABSSSI [67]	Experimental: oral levonadifloxacin (1000 mg BID) or IV levonadifloxacin (800 mg BID); Active comparator: oral linezolid (600 mg BID) or IV linezolid (600 mg BID)	501	When compared to linezolid (IV and oral), levonadifloxacin (IV and oral) exhibited a greater clinical responder rate of 85.2% and 92.7%.; The clinical cure rate was also found to be higher in levonadifloxacin (IV and oral) when compared to linezolid (IV and oral), i.e., 95% versus 89.3%, respectively, for MRSA patients, indicating its favorable microbiological efficacy.; Additionally, in the diabetic foot ulcer subgroup, clinical cure for IV levonadifloxacin was higher than that for linezolid (91.7% versus 76.9%).

ABSSSI: acute bacterial skin and skin structure infections; AM: alveolar macrophage; BID: bis in die/twice a day; ECG: electrocardiogram; ELF: epithelial lining fluid; IV: intravenous; MRSA: methicillin-resistant Staphylococcus aureus; PK: pharmacokinetic.