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A Randomized, Open-label Study of the Pharmacokinetics and Safety of Oral and Intravenous Administration of Omadacycline to Healthy Subjects

Sun, Haiying and Machineni, Surendra Kumar and Ting, Lillian and Praestgaard, Jens and Kuemmell, Andreas and Stein, Daniel and Sunkara, Gangadhar and Kovacs, Steven and 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

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