A dose-finding randomized Phase II study of oral netupitant in combination with palonosetron .75 mg intravenous for the prevention of chemotherapy-induced nausea and vomiting in Japanese patients receiving highly emetogenic chemotherapy

In this Phase II study, no dose–response relationship was observed after oral netupitant administration (30, 100 or 300 mg) in Japanese patients receiving highly emetogenic chemotherapy. Abstract Objective Netupitant is a novel, selective neurokinin-1 receptor antagonist used for prevention of chemotherapy-induced nausea and vomiting, a distressing side effect of chemotherapy. This double-blind, randomized, Phase II study investigated the dose–response of oral netupitant in Japanese patients receiving highly emetogenic chemotherapy. Methods Chemotherapy-naïve patients were randomized (1:1:1) to a single oral netupitant 30-, 100- or 300-mg dose before chemotherapy initiation. Patients received concomitant palonosetron (0.75 mg intravenously [i.v.] Day 1) and dexamethasone (9.9 mg i.v. Day 1, 8 mg orally Days 2–4). Results Overall, 402 patients (30 mg: 134; 100 mg: 135; 300 mg: 133) were treated and evaluable for efficacy and safety. The primary endpoint of overall (0–120 h after chemotherapy administration) complete response (CR) rate (no emesis, no rescue medication) was 64.2%, 60.0% and 54.9% in the 30-, 100- and 300-mg arms, respectively, without statistical significance for dose–response. The safety profile of netupitant was comparable in the three arms. The plasma concentrations of netupitant and its metabolites increased with the dose increase from 30 mg to 300 mg. Conclusions No dose–response relationship of netupitant in terms of overall CR rate was observed in this study. Netupitant was well tolerated at all doses without clinically harmful safety signals observed. Clinical trial registration JapicCTI-142 483