A randomized, open-label, crossover study evaluating bioequivalence of two N-acetylcysteine 2% oral solution formulations in healthy subjects

2018 ◽  
Vol 56 (09) ◽  
pp. 417-425
Author(s):  
Frank Donath ◽  
Marianna Armogida ◽  
Lucy Shneyer
Keyword(s):  
Crossover Study ◽  
Healthy Subjects ◽  
Oral Solution ◽  
Open Label

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

2016 ◽  
pp. AAC.01393-16 ◽  
Author(s):  
Haiying Sun ◽  
Lillian Ting ◽  
Surendra Machineni ◽  
Jens Praestgaard ◽  
Andreas Kuemmell ◽  
...  
Keyword(s):  
Healthy Subjects ◽  
Geometric Mean ◽  
Oral Solution ◽  
Tablet Formulation ◽  
Absolute Bioavailability ◽  
Open Label ◽  
Phase 3 ◽  
Total Exposure ◽  
Oral Formulations ◽  
Tablet Formulations

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 intravenous (IV) administration (and of other oral formulations relative to the Phase 3 tablet) 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 two 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 each other. The Phase 3 tablet produced equivalent exposure to the 100 mg IV dose with geometric mean ratio (90% confidence intervals [CI]) for AUCinfof 1.00 (0.93,1.07). 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.

Sign in / Sign up

Export Citation Format

Share Document