Purpose <p>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.</p> Methods <p>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&#xa0;mg netupitant/0.5&#xa0;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 AUC_0-t bioequivalence of netupitant and palonosetron after a single dose of Test and Reference formulations.</p> Results <p>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 AUC_0-t geometric means of both analytes were similar for the Test and Reference formulations. The 90% confidence interval of the Test/Reference ratios for AUC_0-t of netupitant and palonosetron were within the acceptance range for bioequivalence of 80–125%. The AUC_0-t variability was moderate for netupitant and low for palonosetron. Both formulations were well tolerated.</p> Conclusion <p>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.</p> <p>EUCT Number: 2023–504355-28–00 (25/08/2023).</p>