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Drug Des Devel Ther. 2018 Mar 1;12:429-435. doi: 10.2147/DDDT.S155875. eCollection 2018.

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

Author information

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

Abstract

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

PMID:
29535504
PMCID:
PMC5837372
DOI:
10.2147/DDDT.S155875
[Indexed for MEDLINE]
Free PMC Article

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