Back to Journals » Drug Design, Development and Therapy » Volume 12

Bioequivalence of HTX-019 (aprepitant IV) and fosaprepitant in healthy subjects: a Phase I, open-label, randomized, two-way crossover evaluation

Authors Ottoboni T, Keller MR, Cravets M, Clendeninn N, Quart B

Received 2 November 2017

Accepted for publication 5 January 2018

Published 1 March 2018 Volume 2018:12 Pages 429—435

DOI https://doi.org/10.2147/DDDT.S155875

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Palas Chanda

Peer reviewer comments 3

Editor who approved publication: Dr Tuo Deng


Video abstract presented by Thomas Ottoboni.

Views: 248

Tom Ottoboni,1 Mary Rose Keller,2 Matt Cravets,3 Neil Clendeninn,4 Barry Quart5

1Pharmaceutical and Translational Sciences, Heron Therapeutics, Inc., San Diego, CA, USA; 2Clinical Operations, Heron Therapeutics, Inc., San Diego, CA, USA; 3Biometrics, Heron Therapeutics, Inc., San Diego, CA, USA; 4Clinical, Heron Therapeutics, Inc., San Diego, CA, USA; 5Heron Therapeutics, Inc., San Diego, CA, USA


Introduction: Fosaprepitant, an intravenous (IV) aprepitant prodrug for chemotherapy-induced nausea and vomiting prophylaxis, is associated with systemic and infusion-site reactions attributed in part to its surfactant, polysorbate 80. HTX-019 is an IV aprepitant formulation free of polysorbate 80 and other synthetic surfactants.
Materials and methods: This open-label, single-dose, randomized, two-way crossover bioequivalence study compared pharmacokinetics and safety of HTX-019 and fosaprepitant. Healthy subjects received single-dose HTX-019 (130 mg) or fosaprepitant (150 mg) IV over 30 min, with ≥7-day washout between doses. Blood samples were evaluated for pharmacokinetics and bioequivalence; safety evaluation included treatment-emergent adverse events (TEAEs) and serious adverse events. Ninety-seven of one hundred enrolled subjects completed the study.
Results: Baseline characteristics were comparable between treatment sequences. For HTX-019, mean (percent coefficient of variation) area under the curve (AUC) from time 0 to time of last measurable plasma concentration (AUC0-t), AUC from time 0 to infinity (AUC0-inf), and plasma concentration at 12 h (C12 h) for HTX-019 were 43,729 h*ng/mL (32.7), 45,460 h*ng/mL (36.8), and 988.4 ng/mL (27.5), respectively; corresponding fosaprepitant values were 44,130 h*ng/mL (32.0), 46,163 h*ng/mL (36.6), and 1,022 ng/mL (28.5). Also, 90% CIs (94.186–101.354) were within bioequivalence bounds (80%–125%). Within 1 h following infusion start, one (1%) HTX-019 recipient reported one TEAE, while 20 (20%) fosaprepitant recipients reported 32 TEAEs. Dyspnea occurred in three fosaprepitant recipients (at <1 min in two subjects and at 18 min in one subject, considered study drug related) and one HTX-019 recipient (at 120 h, associated with a respiratory tract infection and considered not related to the study drug). No severe TEAEs, serious adverse events, or deaths occurred; all TEAEs resolved.
Conclusion: HTX-019 was bioequivalent to fosaprepitant and may provide a safer alternative to fosaprepitant for chemotherapy-induced nausea and vomiting prophylaxis.

Keywords: antiemetics, polysorbate 80, safety, surfactant

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]