HTX-019 via 2-min injection or 30-min infusion in healthy subjects
| Autor: | Michael Lauw, Thomas Ottoboni, Kimberly Manhard, Barry D. Quart, Neil J. Clendeninn, Matt Cravets, Mary Rose Keller |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Cancer Research Time Factors Vomiting Antineoplastic Agents Pilot Projects Bioequivalence Fosaprepitant 03 medical and health sciences Young Adult 0302 clinical medicine Pharmacokinetics Neurokinin-1 Receptor Antagonists Medicine Humans Adverse effect Infusions Intravenous Aprepitant Fatigue Cross-Over Studies business.industry Headache Nausea General Medicine Middle Aged Crossover study Healthy Volunteers 030104 developmental biology Treatment Outcome Oncology Tolerability 030220 oncology & carcinogenesis Anesthesia Cohort Injections Intravenous Female business medicine.drug |
| Zdroj: | Future oncology (London, England). 15(8) |
| ISSN: | 1744-8301 |
| Popis: | Aim: HTX-019 (CINVANTI® [aprepitant injectable emulsion]) is a neurokinin 1 receptor antagonist approved for preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV). HTX-019 is free of polysorbate 80 and other synthetic surfactants and showed bioequivalence to and a more favorable safety profile than fosaprepitant when administered as a 30-min infusion in healthy subjects. The shortage of small-volume parenteral solutions led to a recommendation to administer HTX-019 by intravenous push. The objectives were to evaluate pharmacokinetics, tolerability and safety following HTX-019 administration by injection versus infusion. Materials & methods: Study comprised Part A, a pilot Phase I, single-center, randomized, pharmacokinetic, safety and tolerability, open-label study, followed by Part B, a two-sequence crossover study of HTX-019 130 mg in healthy adults, via injection and infusion. Blood samples were evaluated for aprepitant pharmacokinetics and bioequivalence. Safety evaluations included treatment-emergent adverse events (TEAEs), vital signs, clinical laboratory testing and electrocardiograms. Results: In Part A, 24 subjects were randomly assigned to three cohorts (n = 8 per cohort) and received HTX-019 130 mg, administered intravenously over 15 min (cohort 1), 5 min (cohort 2) or 2 min (cohort 3). Progression to Part B occurred after acceptable tolerability was established in cohorts 2 and 3. In Part B, 50 randomized subjects received a 2-min injection (9 ml/min) and 30-min infusion (296 ml/h) of HTX-019 130 mg. Bioequivalence was demonstrated for HTX-019 injection and infusion. Both administration methods via a peripheral line were well tolerated; eight subjects experienced 11 TEAEs (six related) following injection and nine experienced 14 TEAEs (nine related) following infusion. Headache and fatigue were the most prevalent treatment-related TEAEs; one subject per group experienced feeling hot ≤30 min after drug administration. Conclusion: Pharmacokinetic and tolerability profiles of 2-min HTX-019 injection support this potential alternative administration method for CINV prevention. |
| Databáze: | OpenAIRE |
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