Sun, Haiying, Machineni, Surendra Kumar, Ting, Lillian, Praestgaard, Jens, Kuemmell, Andreas, Stein, Daniel, Sunkara, Gangadhar, Kovacs, Steven, Villano, Stephen and Tanaka, Ken (2016) A Randomized, Open-label Study of the Pharmacokinetics and Safety of Oral and Intravenous Administration of Omadacycline to Healthy Subjects. Antimicrobial Agents and Chemotherapy, Online (Online). pp. 1-22. ISSN 1098-6596

Abstract

Omadacycline is a first in class aminomethylcycline antibiotic with microbiological activity against Gram-positive and Gram-negative aerobes and anaerobes, and atypical bacteria that is being developed for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). The bioavailability of two oral tablet formulations relative to intravenous (IV) administration was investigated in an open-label, randomized, four-period, crossover study in healthy subjects age 18-50 years. Subjects received omadacycline 100 mg IV, 300 mg oral as different tablet formulations with different dissolution profiles, and a 300 mg as an oral solution. Plasma omadacycline concentrations were determined using a validated LC/MS/MS method. Twenty of 24 subjects completed all treatment periods. Both tablet formulations produced equivalent total exposure relative to the 100 mg IV dose with geometric mean ratios (90% confidence intervals [CI]) for AUCinf of 1.00 (0.93,1.07) and 0.96 (0.90,1.03), respectively. Absolute bioavailability of the tablets was approximately 34.5%. Intersubject variability was consistent among the oral formulations (~20-25%). Single oral and IV doses of omadacycline were well tolerated; three subjects experienced mild adverse events (dizziness, nausea, vomiting) that resolved without intervention. A 300 mg dose of the tablet formulation of omadacycline intended for use in phase 3 studies produced total exposure equivalent to that of a 100 mg IV dose.

Item Type:	Article
Date Deposited:	10 Nov 2016 00:45
Last Modified:	10 Nov 2016 00:45
URI:	https://oak.novartis.com/id/eprint/28424