L. Sayegh,1 J. M. Paquette,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 formulation of ondansetron for management of chemo- and radiotherapy-induced nausea and vomiting. This study assessed the bioavailability of a 24 mg MR formulation of RHB-102, with respect to a commercially-available 8 mg ondansetron IR formulation administered as 24 mg qd or 8 mg bid.
METHODS: In this open-label, three-period, three-sequence, crossover study, healthy subjects (n=18) were randomized to each oral treatment: A (RHB-102 24 mg qd for 5 days), B (Reference 8 mg bid, Day 1: 8-h interval, Day 2: 12-h interval) and C (Reference as a single 24 mg dose). Blood samples were collected over 24 h during the first days and for 48 h after the last RHB-102 dose. Safety was evaluated through AEs, vital signs, ECG, physical exam and laboratory tests. Ondansetron was assayed with a validated HPLC method (MS/MS detection). PK parameters were calculated using NCA.
RESULTS: AUC0-24 of RHB-102 was higher than treatment B on Day 1 and Day 2 (D1: 638 vs. 540 ng h/mL, D2: 797 vs. 610 ng h/mL, p<0.05). Ondansetron levels were generally similar to or higher after RHB-102 administration than after treatment B. AUC0-24 and Cmax of RHB-102 on Day 1 were lower than treatment C (AUC: 638 vs. 1058 ng h/mL, Cmax: 54 vs. 140 ng/mL; p<0.05). However, concentrations 24 h post-dose were higher for RHB-102 than for treatments B and C on Day 1 (11.5, 8.7 and 8.1 ng/mL; p<0.05). Steady-state was reached between Day 4 and Day 5, when AUC0-24 stabilized at ≈ 30%. The frequency of AEs was comparable between treatments. No SAEs were reported.
CONCLUSION: Bioavailability of RHB-102 is lower than ondansetron 24 mg qd and non-inferior to that of ondansetron 8 mg bid, the approved regimen in moderately emetogenic chemotherapy. Despite the longer RHB-102 treatment duration, the safety profiles were similar for all treatments.