1555P - Pharmacokinetic (PK) study of a single oral dose of NEPA in Chinese healthy volunteers (HVs)

Date 10 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Pharmacology
Supportive Care
Palliative and Supportive Care
Presenter Rui Chen
Citation Annals of Oncology (2017) 28 (suppl_5): v543-v567. 10.1093/annonc/mdx388
Authors R. Chen1, S. Chessari2, C. Lanzarotti2, A. Bernareggi3, P. Hu1
  • 1Clinical Pharmacology Research Center, Peking Union Medical College Hospital (PUMCH), 100032 - Beijing/CN
  • 2Corporate Clinical Development, Helsinn Healthcare SA, Lugano/CH
  • 3R & D Innovation And Strategy, Helsinn Healthcare SA, Lugano/CH



NEPA, a combined neurokinin-1 receptor antagonist (RA) netupitant (NETU; 300 mg) and 5-HT3–RA palonosetron (PALO; 0.50 mg), is the first approved oral combination antiemetic. NEPA has shown superior efficacy over PALO in preventing chemotherapy-induced nausea and vomiting (CINV), in cisplatin and AC-chemotherapy settings, leading to its approval in the US and Europe (with 85% of patients Caucasian in the clinical trials). A recent phase 3 registration trial in Asian patients demonstrated non-inferiority of a single oral dose of NEPA in preventing CINV compared with a 3-day oral aprepitant/granisetron regimen. The present study was undertaken to assess the PK profile of NETU and PALO in Chinese HVs.


Eligible HVs received a single oral dose of NEPA administered as a hard gelatin capsule on day 1, after 10-h fasting. Blood samples for PK analysis were collected pre-dose and at 1, 2, 3, 4, 4.5, 5, 5.5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168, 192, and 240 h post-dose. The plasma concentration of NETU and PALO was determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS). PK parameters were estimated via non-compartmental analysis using the WinNonlin 6.3 software (Certara Inc., Princeton, NJ, USA).


A total of 18 subjects were enrolled (16 male; median body weight 62.7 kg [52.6–75.2 kg]; median age 27 y [21–37 y]). After a single oral dose of NEPA, mean (±SD) values of peak plasma concentration (Cmax) for NETU were 698±217 ng/mL at a median of 4.5 h (Tmax; 3–6 h), with mean (±SD) overall exposure up to the last measurable concentration (AUC0–t) of 20.2±3.93 h*mg/L. PALO plasma concentrations reached mean (±SD) Cmax of 1800±252 ng/mL at 3 h (2–6 h) with mean (±SD) AUC0–t of 77.6±13.3 h*µg/L. NEPA was well tolerated in all HVs.


In Chinese HVs the PK profile of NETU was comparable to that previously observed in Caucasians. For PALO, Cmax and AUC0–t were higher in these Chinese HVs compared to Caucasians, which may be explained by CYP2D6 (involved in the metabolism of PALO) polymorphism. However, the similar efficacy and safety for PALO and NEPA in pivotal studies in both populations suggests that the higher exposure to PALO in Chinese HVs is unlikely to be clinically relevant.

Clinical trial identification

Legal entity responsible for the study

Helsinn Healthcare SA


Helsinn Healthcare SA


S. Chessari, C. Lanzarotti, A. Bernareggi: Helsinn Healthcare SA employee


All other authors have declared no conflicts of interest.