HTX-019 via 2-min injection or 30-min infusion in healthy subjects.

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HTX-019 via 2-min injection or 30-min infusion in healthy subjects.

Future Oncol. 2018 Dec 21;:

Authors: Ottoboni T, Lauw M, Keller MR, Cravets M, Manhard K, Clendeninn N, Quart B

Abstract
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; 8 subjects experienced 11 TEAEs (6 related) following injection and 9 experienced 14 TEAEs (9 related) following infusion. Headache and fatigue were the most prevalent treatment-related TEAEs; 1 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.

PMID: 30574797 [PubMed - as supplied by publisher]

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