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

  title={Randomized, Open-Label Study of the Pharmacokinetics and Safety of Oral and Intravenous Administration of Omadacycline to Healthy Subjects},
  author={Haiying Sun and Lillian S. L. Ting and Surendra Machineni and Jens Praestgaard and Andreas Kuemmell and Daniel S. Stein and Gangadhar Sunkara and Steven J. Kovacs and Stephen A. Villano and S. Ken Tanaka},
  journal={Antimicrobial Agents and Chemotherapy},
  pages={7431 - 7435}
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 a phase 3 tablet formulation relative to that obtained via intravenous (i.v.) administration (and of other oral formulations relative… Expand
Safety and Pharmacokinetics of the Aminomethylcycline Antibiotic Omadacycline Administered to Healthy Subjects in Oral Multiple-Dose Regimens
All doses were generally well tolerated, but the 600-mg dose was associated with more gastrointestinal adverse events than the other doses, and the kinetics of omadacycline plasma accumulation were similar between dose levels. Expand
Pharmacokinetics and Pharmacodynamics of Oral and Intravenous Omadacycline
  • K. Rodvold, M. Pai
  • Medicine
  • Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2019
Omadacycline formulations approved in the United States for treating acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia in adults support once-daily dosing, and fAUC0–24/MIC ratio is identified as the parameter that correlates with in vivo efficacy. Expand
Pharmacokinetics and Safety of Omadacycline in Subjects with Impaired Renal Function
This study demonstrates that no dose adjustment is necessary for omadacycline in patients with impaired renal function or on days when patients are receiving hemodialysis, and generally safe and well tolerated in both ESRD and healthy subjects. Expand
The Effect of Verapamil, a P-gp Inhibitor, on the Pharmacokinetics, Safety, and Tolerability of Omadacycline in Healthy Adults: A Phase I, Open-Label, Single-Sequence Study
Findings suggest that, if given with a known P-gp inhibitor, dose adjustment of oral omadacycline is not warranted based on small increases in absorption and systemic exposure. Expand
Omadacycline: A Review of the Clinical Pharmacokinetics and Pharmacodynamics
A population pharmacokinetic model was developed with data from healthy subjects and infected patients and used to establish interpretive criteria for in vitro susceptibility testing and dosing regimens of omadacycline for treating acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Expand
An Open-Label Study of the Impact of Hepatic Impairment on the Pharmacokinetics and Safety of Single Oral and Intravenous Doses of Omadacycline
It is suggested that no omadacycline dose adjustment is warranted in patients with hepatic impairment and healthy subjects following i.v. or oral administration, and asymptomatic increases in heart rate were observed; none was considered an AE. Expand
Pharmacokinetics, Safety, and Clinical Outcomes of Omadacycline in Women with Cystitis: Results from a Phase 1b Study
Preliminary results indicate that omadacycline warrants further evaluation in larger controlled UTI studies, as it appears to be safe and well tolerated. Expand
Randomized, Double-Blind, Placebo- and Positive-Controlled Crossover Study of the Effects of Omadacycline on QT/QTc Intervals in Healthy Subjects
Omadacycline had no effect on cardiac conduction (PR and QRS intervals) but caused an increase in heart rate and the possibility of an effect on placebo-corrected ΔQTcS exceeding 10 ms can be excluded at omadacyCline concentrations in plasma of up to ∼8 μg/ml. Expand
Omadacycline: A Novel Oral and Intravenous Aminomethylcycline Antibiotic Agent
Omadacycline possesses broad-spectrum antibacterial activity against Gram-positive and Gram-negative aerobic, anaerobic, and atypical bacteria, and remains active against bacterial isolates possessing common tetracyCline resistance mechanisms such as efflux pumps and ribosomal protection proteins. Expand
Omadacycline: A New Tetracycline Antibiotic
Omadacycline provides clinicians with an additional parenteral and oral option for the treatment of adults with ABSSSI and CABP, and is well tolerated, with nausea being a common adverse effect, but is associated with food and drug interactions. Expand


Pharmacokinetics and bioequivalence study of doxycycline capsules in healthy male subjects.
Bioequivalence between test and reference preparation was demonstrated since for both parameters AUC and Cmax the 90% confidence intervals of the T/R ratios of logarithmically transformed data were in the generally accepted range of 80 0%-125%. Expand
Bioequivalence study of two minocycline capsule formulations in healthy volunteers.
It can be concluded that the two minocycline capsules (test drug and reference drug) are bioequivalent in terms of the rate and extent of absorption. Expand
A Randomized, Evaluator-Blind, Phase 2 Study Comparing the Safety and Efficacy of Omadacycline to Those of Linezolid for Treatment of Complicated Skin and Skin Structure Infections
It is concluded that omadacycline is well tolerated in cSSSI patients and that this aminomethylcycline has potential to be an effective treatment for serious skin infections. Expand
In Vitro and In Vivo Assessments of Cardiovascular Effects with Omadacycline
Overall, omadacycline appears to attenuate the parasympathetic influence on the heart rate but has a low potential to induce cardiac arrhythmia or to have clinically significant cardiovascular toxicity. Expand
In Vitro and In Vivo Antibacterial Activities of Omadacycline, a Novel Aminomethylcycline
  • A. Macone, B. Caruso, +5 authors S. B. Levy
  • Biology, Medicine
  • Antimicrobial Agents and Chemotherapy
  • 2013
Omadacycline demonstrated in vitro activity against a broad range of Gram-positive and select Gram-negative pathogens, including resistance determinant-containing strains, and this activity translated to potent efficacy in vivo, demonstrating potent in vivo efficacy. Expand
Mechanism of Action of the Novel Aminomethylcycline Antibiotic Omadacycline
ABSTRACT Omadacycline is a novel first-in-class aminomethylcycline with potent activity against important skin and pneumonia pathogens, including community-acquired methicillin-resistantExpand
Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines.
Though incompletely understood, the pharmacodynamic properties of the tetracyclines and glycylcyclines are summarized. Expand
In Vitro Evaluation of PTK796 Activity Tested against Staphylococcus aureus, Including Hospital- and Community-Associated MRSA Strains from the USA and Europe
PTK796 is a broad-spectrum agent with proven efficacy in animal models for treating clinically prevalent infections caused by Gram-positive and Gram-negative bacteria, including those with multidrug resistance (MDR). Expand
Pharmacokinetics of intravenous and oral PTK796, a new aminomethylcycline antibiotic, abstr K-124
  • Abstr 50th Intersci Conf Antimicrob Agents Chemother
  • 2010
In vitro and in vivo assessment of cardiovascular effects with omadacycline. Antimicrob Agents Chemother http://dx.doi.org/10.1128/AAC.00320-16
  • 2016