title: Effect of Food on the Bioavailability of Omadacycline in Healthy Participants.
abstract: Omadacycline is a first-in-class aminomethylcycline antibiotic being evaluated in phase 3 studies as oral and intravenous monotherapy for bacterial infections. This was a phase 1, randomized, open-label, 4-period, crossover study that evaluated the effect of food consumption on the bioavailability of omadacycline. Healthy participant were randomized to 1 of 4 sequences, which included the following predose conditions in different orders (A) ≥6-hour fast, (B) high-fat, nondairy meal 4 hours before dosing, (C) high-fat, nondairy meal 2 hours before dosing, and (D) high-fat meal containing dairy 2 hours before dosing. Participants received a single 300-mg oral dose of omadacycline during each treatment period; periods were separated by ≥5 days. Blood samples for pharmacokinetic (PK) analysis were collected over 24 hours after each dose, and safety assessments were performed during each treatment period. Least-squares mean and 90% confidence intervals were compared for fed state vs fasted state. Thirty-one participants were included in the PK analysis. Fasted AUC0-∞, AUC0-t, and AUC0-24were 10.2, 7.2, and 7.2 μg·h/mL, respectively, and Cmaxwas 0.6 μg/mL. Compared with a fasted dose, bioavailability was reduced by 15% to 17% by a nondairy meal 4 hours before dosing, 40% to 42% by a nondairy meal 2 hours before dosing, and 59% to 63% for a dairy meal 2 hours before dosing. Two participants experienced adverse events (mild nausea, mild somnolence). A 300-mg oral dose of omadacycline administered within 2 to 4 hours after food had reduced bioavailability compared with the fasted state. Oral omadacycline should be administered in a fasted state.
authors.affiliation: Paratek Pharmaceuticals, King of Prussia, PA, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Tzanis
authors.affiliation: Paratek Pharmaceuticals, King of Prussia, PA, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Manley
authors.affiliation: Paratek Pharmaceuticals, King of Prussia, PA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Villano
authors.affiliation: Paratek Pharmaceuticals, King of Prussia, PA, USA.
authors.forename: S Ken
authors.initials: SK
authors.lastname: Tanaka
authors.affiliation: Paratek Pharmaceuticals, King of Prussia, PA, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Bai
authors.affiliation: Paratek Pharmaceuticals, King of Prussia, PA, USA.
authors.forename: Evan
authors.initials: E
authors.lastname: Loh
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004041:Dietary Fats / Q000378:metabolism; D005215:Fasting / Q000502:physiology; D005260:Female; D018565:Food-Drug Interactions; D006207:Half-Life; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D013754:Tetracyclines / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D004041:Dietary Fats; D013754:Tetracyclines; C000591640:omadacycline
keywords: bioavailability; fasted; food effect; omadacycline; pharmacokinetics