Safety of HTX-019 (intravenous aprepitant) and fosaprepitant in healthy subjects

• Published in: Future oncology (London, England) Vol. 14; no. 27; pp. 2849 - 2859
• Main Authors: Ottoboni, Tom, Lauw, Michael, Keller, Mary Rose, Cravets, Matt, Manhard, Kimberly, Clendeninn, Neil, Quart, Barry
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.11.2018
• Subjects: Adult; Anaphylaxis; antiemetics; Antiemetics - administration & dosage; Antiemetics - adverse effects; Antineoplastic Agents - adverse effects; aprepitant; Aprepitant - administration & dosage; Aprepitant - adverse effects; Cancer therapies; Chemotherapy; Cross-Over Studies; Drug dosages; Dyspnea - chemically induced; Dyspnea - epidemiology; Family medical history; FDA approval; Female; Healthy Volunteers; Humans; Infusions, Intravenous; Male; Middle Aged; Morpholines - administration & dosage; Morpholines - adverse effects; Nausea; Nausea - chemically induced; Nausea - drug therapy; Neoplasms - drug therapy; Neurokinin-1 Receptor Antagonists - administration & dosage; Neurokinin-1 Receptor Antagonists - adverse effects; Oncology; Polyethylene glycol; safety; Studies; Surfactants; Treatment Outcome; Vomiting; Vomiting - chemically induced; Vomiting - drug therapy; Young Adult; United States > US; aprepitant; safety; antiemetics
• ISSN: 1479-6694; 1744-8301
• DOI: 10.2217/fon-2018-0311

Evaluate safety of HTX-019, a novel polysorbate 80- and synthetic surfactant-free intravenous formulation of neurokinin 1 receptor antagonist aprepitant for chemotherapy-induced nausea and vomiting. Two open-label, randomized, two-way crossover studies evaluated treatment-emergent adverse events (TEAEs) in 200 healthy subjects. Subjects received HTX-019 130 mg (30-min infusion) and fosaprepitant 150 mg (20- or 30-min infusion), with ≥7-day washout between doses. Less than or equal to 30 min after start of infusion, TEAEs occurred in 5 (3%) HTX-019 and 30 (15%) fosaprepitant recipients. No HTX-019 recipients had infusion-site adverse events, versus 15 (8%) fosaprepitant recipients. Treatment-related dyspnea occurred in one HTX-019 and six fosaprepitant recipients. No severe/serious TEAEs occurred; all TEAEs resolved. HTX-019 may provide a safer aprepitant formulation than fosaprepitant for chemotherapy-induced nausea and vomiting prevention.