PII-035 - A BIOEQUIVALENCE AND FOOD EFFECT CLINICAL STUDY OF ZOLIFLODACIN, FIRST-IN-CLASS ORAL ANTIBIOTIC, BEING DEVELOPED FOR THE TREATMENT OF UNCOMPLICATED GONORRHEA

N. Rayad¹, A. Luckey², M. Heep², S. Delhomme³, G. Kornmann², K.B. Larson⁴, J. Mueller⁴, J. O'Donnell⁴, S. O'Brien², R. Fuhr⁵, J.Y. Gillon³; ¹Parexel International, ²Global Antibiotic R&D Partnership (GARDP), ³Drugs for Neglected Diseases initiative (DNDi), ⁴Innoviva Specialty Therapeautics Inc., ⁵Parexel International GmbH.

Background: Uncomplicated gonorrhea is caused by Neisseria gonorrhoeae and is the second most common sexually transmitted infection worldwide, with drug-resistant N. gonorrhoeae being categorized as an “Urgent Threat” by the CDC. Zoliflodacin (Zoli) is a spiropyrimidinetrione antibacterial agent, and first-in-class oral gyrase inhibitor being developed for the treatment of uncomplicated gonorrhea. A Phase 1 clinical study was conducted to assess the bioequivalence (BE) of two formulations: test (commercial) formulation developed following API and drug product optimization and scale-up compared to the Phase 3 formulation. The effect of food on pharmacokinetic (PK) properties of zoliflodacin was also evaluated.

Methods: Thirty-two healthy adults were randomized to receive either ZoliDr (test [commercial]) or ZoliPa (reference [Phase 3]) under fed and fasted conditions in a 4x4, crossover design. A moderate-fat, moderate-calorie diet was used. Blood samples were collected over 48 hours post-dose and zoliflodacin plasma concentrations were analyzed using a validated liquid chromatography-tandem mass spectrometry assay. PK parameters were calculated using non-compartmental analysis. A statistical analysis was conducted to determine the BE and food effect according to regulatory guidance.

Results: The geometric mean ratio (GMR) and corresponding 90% confidence intervals (CIs) of PK parameters of ZoliDr vs ZoliPa were within the BE range of 80.00% - 125.00% under fasted and fed conditions (Table 1).
Food increased zoliflodacin exposure by approximately1.5-fold, with a 1.5-hour delay to reach maximum concentration for both formulations. The GMR (fed/fasted) and the 90% CIs for PK parameters were outside the range of 80.00% - 125.00%, indicating a positive food effect.
There were no clinically significant changes in laboratory values, vital signs, or ECGs. There were no deaths or serious treatment-emergent adverse events (TEAEs). One subject was withdrawn due to a TEAE (rash), which resolved.

Conclusion: Bioequivalence was established between the ZoliDr (test) and ZoliPa (reference) under both fasted and fed conditions. Zoliflodacin exposures increased when administered with a moderate-fat, moderate-calorie meal. Both ZoliDr and ZoliPa were generally well-tolerated, with one discontinuation due to rash, and no serious TEAEs reported.