L. Sayegh,1 R. Essalihi,1 E. Sicard,1 M. Noumeir,1 J. Massicotte,1 M. Lefebvre,1 R. Fathi,2 T. F. Plasse,2 G. Raday2; 1Algorithme Pharma, Laval, QC, Canada, 2RedHill Biopharma Ltd., Tel-Aviv, Israel
BACKGROUND: RHB-102 is a new drug product developed for the management of nausea and vomiting induced by cytotoxic chemotherapy and radiotherapy. A study was conducted to evaluate the influence of food on the PK of the once-daily 24 mg extended-release RHB-102 formulation.
METHODS: Fourteen healthy subjects were randomized in a single center, laboratory-blinded, two‑treatment, two-sequence, single-dose, crossover study. Blood samples were collected over a 72 h period and a washout period of 7 days separated drug administrations. Safety was evaluated through AEs, vital signs, ECG, physical examination and laboratory tests. Ondansetron was assayed with a validated HPLC-MS/MS method and PK parameters were evaluated using a NCA approach. The geometric mean ratio of the main PK parameters was derived using an ANOVA model.
RESULTS: The bioavailability of RHB-102 administered after a standardized high fat meal was greater than in fasted subjects, as indicated by the Cmax and AUC fed to fast ratio of geometric LSmeans (90% CI): 140% [128, 152] and 120% [109, 133], respectively. The difference in Cmax is somewhat larger and the difference in AUC is similar to those noted with IR ondansetron. Tmax was delayed under fed conditions (by 3 h). In contrast, the Thalf and concentrations at 24-h post-dose were similar with and without food (10.29 to 10.97 h and 12.9 to 13.8 ng/mL, respectively). There were no SAEs, and treatment was well tolerated in both states.
CONCLUSION: Consistent with the PK of the commercially-available 8 mg ondansetron IR formulation, food delayed the absorption of RHB-102, and increased the maximal concentrations and extent of absorption of ondansetron. Despite these increases, the number and severity of adverse events was lower under fed conditions.