Bioequivalence of netupitant and palonosetron (NEPA) oral suspension and hard capsules in healthy individuals: results from an open-label, randomized, two-treatment, four-period, two-sequence replicative design trial.

PURPOSE: NEPA, a fixed-antiemetic combination of netupitant and palonosetron, is available via two administration routes (oral and intravenous). A new oral suspension was developed to offer a more convenient option for patients. This study evaluated the bioequivalence between the oral capsule and the oral suspension.

METHODS

Open-label, randomized, single-center phase I trial conducted according to a two-treatment, four-period, two-sequence replicative design. Two treatments were investigated for bioequivalence: a 10-mL oral suspension (Test [T]) and the hard capsule (Reference [R]), both containing 300 mg netupitant/0.5 mg palonosetron. Healthy individuals were randomized (1:1) to receive two doses of both Test and Reference formulations, in either T-R-T-R or R-T-R-T sequence. The primary objective was to demonstrate AUC0-t bioequivalence of netupitant and palonosetron after a single dose of Test and Reference formulations.

RESULTS

In total, 72 participants were included. The geometric mean plasma concentration-time profiles of netupitant and palonosetron were similar for the Test and Reference formulations. The AUC0-t geometric means of both analytes were similar for the Test and Reference formulations. The 90% confidence interval of the Test/Reference ratios for AUC0-t of netupitant and palonosetron were within the acceptance range for bioequivalence of 80-125%. The AUC0-t variability was moderate for netupitant and low for palonosetron. Both formulations were well tolerated.

CONCLUSION

The NEPA oral suspension is pharmacokinetically bioequivalent to the capsule formulation in healthy individuals, with no new safety concerns. These findings support NEPA oral suspension as a potentially beneficial option for patients who prefer an oral suspension over a hard capsule and for those with swallowing difficulties. EUCT Number: 2023-504355-28-00 (25/08/2023).