title: Evaluation of the effect of food and age on the pharmacokinetics of oral netupitant and palonosetron in healthy subjects: A randomized, open-label, crossover phase 1 study.
abstract: Antiemetic treatment compliance is important to prevent chemotherapy-induced nausea and vomiting, a feared chemotherapy side effect. NEPA, a new oral fixed combination of netupitant, a highly selective NK1 receptor antagonist (RA), and palonosetron, a second-generation 5-HT3 RA, targets dual antiemetic pathways with a single dose. This study investigated the effect of food intake and age on NEPA pharmacokinetics (PK) and safety. In this open-label, single-center, randomized, phase 1 study, 24 adults (18-45 years) received NEPA in a fed or fasted state during the first treatment period and in the alternative state in the next treatment period. Twelve elderly subjects (≥65 years) received NEPA in a fasted state. Blood samples were taken for netupitant and palonosetron PK analysis. In the fed condition, netupitant plasma exposure increased, whereas palonosetron PK parameters were not affected. Furthermore, elderly subjects showed increased netupitant and palonosetron exposure compared with adults. All adverse events were mild/moderate, with constipation and headache the most common. Although food intake and age altered NEPA PK, dose adjustments were not needed, as netupitant and palonosetron exposure increases did not lead to safety concerns in healthy subjects.
authors.affiliation: Helsinn Healthcare SA, Lugano/Pazzallo, Switzerland.
authors.forename: Selma
authors.initials: S
authors.lastname: Calcagnile
authors.affiliation: Helsinn Healthcare SA, Lugano/Pazzallo, Switzerland.
authors.forename: Corinna
authors.initials: C
authors.lastname: Lanzarotti
authors.affiliation: Helsinn Healthcare SA, Lugano/Pazzallo, Switzerland.
authors.forename: Michaela
authors.initials: M
authors.lastname: Gutacker
authors.affiliation: CRS Clinical Research Services Mannheim GmbH, Grünstadt, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Jakob-Rodamer
authors.affiliation: CRS Clinical Research Services Mannheim GmbH, Mannheim, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Peter Kammerer
authors.affiliation: CRS Clinical Research Services Mannheim GmbH, Mannheim, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Timmer
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000367:Age Factors; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004338:Drug Combinations; D005215:Fasting / Q000097:blood; D005260:Female; D018565:Food-Drug Interactions; D005858:Germany; D064368:Healthy Volunteers; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011812:Quinuclidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000932:Antiemetics; D004338:Drug Combinations; D007546:Isoquinolines; D011725:Pyridines; D011812:Quinuclidines; C000595957:netupitant, palosentron drug combination
keywords: NEPA; food/age effect study; netupitant; palonosetron; pharmacokinetics