Crossover safety study of aprepitant: 2-min injection vs 30-min infusion in cancer patients receiving emetogenic chemotherapy
Authors Navari RM, Mosier MC
Received 16 January 2019
Accepted for publication 10 March 2019
Published 30 April 2019 Volume 2019:12 Pages 3277—3284
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Ms Aruna Narula
Peer reviewer comments 2
Editor who approved publication: Dr Sanjay Singh
Rudolph M Navari,1 Michael C Mosier2
1Department of Medicine, University of Alabama Birmingham, Birmingham, AL, USA; 2Biostatistics, EMB Statistical Solutions, LLC, Overland Park, KS, USA
Introduction: HTX-019 (CINVANTI®) is a novel injectable emulsion formulation of the neurokinin 1 receptor antagonist (RA) aprepitant, approved for preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV). HTX-019 has demonstrated a tolerable safety profile when administered via 30-min intravenous (IV) infusion and 2-min IV injection in healthy volunteers. This prospective study evaluated the safety of HTX-019 administered via 30-min IV infusion and 2-min injection (IV push) in patients with cancer.
Materials and methods: This prospective single-center, randomized, safety, 2-sequence, 2-period, crossover study evaluated HTX-019 130 mg within a guideline-recommended 3-drug regimen for CINV prophylaxis in patients receiving highly (HEC) or moderately emetogenic chemotherapy (MEC). Treatment-emergent adverse events (TEAEs) were assessed at 0–30 (primary endpoint), 30–60, and >60 mins (chemotherapy administration period) following the initiation of the HTX-019 administration, focusing on infusion-site adverse events and hypersensitivity reactions (dyspnea, anaphylaxis).
Results: Among 135 patients (35 MEC, 100 HEC), the most common diagnoses were ovarian (32), lung (17), endometrial (17), and colorectal (15) cancer. Patients were randomized 1:1 to a 2-min injection and a 30-min infusion of HTX-019 (sequence AB or BA), followed by a 5-hydroxytryptamine type 3 RA IV (palonosetron 0.25 mg for 30 s or ondansetron 8–16 mg for 5–10 mins), dexamethasone IV (8–12 mg for 15 mins), and the chemotherapy regimen. Both administration methods were generally well tolerated. No TEAEs occurred within 30 mins after start of HTX-019 administration. All TEAEs occurred during chemotherapy administration; 2 patients experienced 2 TEAEs following injection, and 5 experienced 8 TEAEs following infusion. Three adverse events following infusion (2 dyspnea, 1 throat closing) were considered serious. No TEAEs were considered related to HTX-019.
Conclusion: Short injection of HTX-019 has a tolerable safety profile in patients with cancer, and represents an alternative method of HTX-019 administration for CINV prevention.
Keywords: aprepitant, bag shortage, CINV, HTX-019, real world, short injection
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