Effect of food on the pharmacokinetics of zoliflodacin granules for oral suspension: Phase I open-label randomized cross-over study in healthy subjects.

ABSTRACT

Gonorrhea is a sexually transmitted infection for which antibiotic treatment options have declined due to increasing antibiotic resistance. Zoliflodacin, an investigational oral spiropyrimidinetrione antibiotic with activity against Neisseria gonorrhoeae strains that are multidrug-resistant, including to third-generation cephalosporins, is in phase III development for uncomplicated gonorrhea. This phase I, parallel, open-label, randomized, crossover study in healthy adults evaluated the effect of food on the pharmacokinetics of single 3 or 4 g doses of zoliflodacin administered as granules for oral suspension in the fasted state or after consumption of a standardized high-fat meal. Forty-seven out of 48 randomized subjects completed the study. Oral administration of zoliflodacin with food delayed the absorption rate, compared with fasted state, with time to maximum concentration (Tmax ) increasing from 3 to 6 h for the 3 g dose, and 2.5 to 4 h for the 4 g dose, but had no impact on the elimination of zoliflodacin. The maximum concentration (Cmax ) and area under the plasma concentration-time curve from time 0 to 24 h (AUC(0-24) ) significantly increased with food by 52% and 94% for the 3 g dose, and by 89% and 108% for the 4 g dose. Forty-two percent of participants reported a total of 34 treatment-emergent adverse events (TEAEs), which were all considered mild in severity. Headache was the most common TEAE (22/48 subjects, 45.8%) and the only TEAE reported in more than one subject. In conclusion, administration of single 3 and 4 g doses of zoliflodacin as granules for oral suspension, with a high-fat meal was well-tolerated and resulted in statistically significant increases in peak and overall systemic exposure to zoliflodacin.