| Title |
Bioequivalence of HTX-019 (aprepitant IV) and fosaprepitant in healthy subjects: a Phase I, open-label, randomized, two-way crossover evaluation
|
|---|---|
| Published in |
Drug Design, Development and Therapy, March 2018
|
| DOI | 10.2147/dddt.s155875 |
| Pubmed ID | |
| Authors |
Tom Ottoboni, Mary Rose Keller, Matt Cravets, Neil Clendeninn, Barry Quart |
| Abstract |
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. 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. 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. HTX-019 was bioequivalent to fosaprepitant and may provide a safer alternative to fosaprepitant for chemotherapy-induced nausea and vomiting prophylaxis. |
X Demographics
The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Netherlands | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 20 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 20 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 4 | 20% |
| Student > Master | 2 | 10% |
| Student > Doctoral Student | 1 | 5% |
| Student > Bachelor | 1 | 5% |
| Student > Ph. D. Student | 1 | 5% |
| Other | 3 | 15% |
| Unknown | 8 | 40% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 4 | 20% |
| Biochemistry, Genetics and Molecular Biology | 2 | 10% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 10% |
| Chemistry | 2 | 10% |
| Psychology | 1 | 5% |
| Other | 0 | 0% |
| Unknown | 9 | 45% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 March 2018.
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#20,663,600
of 25,382,440 outputs
Outputs from Drug Design, Development and Therapy
#1,436
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Outputs of similar age
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Outputs of similar age from Drug Design, Development and Therapy
#33
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