HTX-019 via 2-min injection or 30-min infusion in healthy subjects.
Future Oncol
; 15(8): 865-874, 2019 Mar.
Article
em En
| MEDLINE
| ID: mdl-30574797
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; 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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vômito
/
Antagonistas dos Receptores de Neurocinina-1
/
Aprepitanto
/
Náusea
/
Antineoplásicos
Tipo de estudo:
Clinical_trials
/
Guideline
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article