Pharmacokinetics, pharmacodynamics, and tolerability of subcutaneous administration of a novel glycoprotein IIb/IIIa inhibitor, RUC-4, in patients with ST-segment elevation myocardial infarction

Willem L. Bor, Kai L. Zheng, Anne H. Tavenier, C. Michael Gibson, Christopher B. Granger, Ohad Bentur, Rita Lobatto, Sonja Postma, Barry S. Coller, Arnoud W. J. van 't Hof, Jurrien M. Ten Berg*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Web of Science)

Abstract

Background: Pre-hospital platelet inhibition in patients with ST-segment elevation myocardial infarction (STEMI) may improve outcomes. RUC-4 is a novel, second-generation glycoprotein IIb/IIIa inhibitor designed for first-point-of-medical-contact treatment for STEMI by subcutaneous injection.

Aims: The open-label, phase 2A, CEL-02 trial aimed to assess the pharmacodynamics (PD), pharmacokinetics (PK), and tolerability of RUC-4 in STEMI patients undergoing primary PCI (pPCI).

Methods: A total of 27 STEMI patients received a weight-adjusted subcutaneous injection of RUC-4 before pPCI in escalating doses (0.075 mg/kg [n = 8], 0.090 mg/kg [n = 9], or 0.110 mg/kg [n = 10]).

Results: The primary PD endpoint of high-grade (>= 77%) inhibition of the VerifyNow iso-TRAP assay at 15 minutes was met in 3/8, 7/8, and 7/8 patients in the three cohorts with a dose-response relationship (mean inhibition [min -max] of 77.5% [65.7%-90.6%], 87.5% [73.8%-93.1%], and 91.7% [76.4%-99.3%], respectively; ptrend = 0.002). Fifty percent (50%) inhibition remained after 89.1 (38.0-129.7), 104.2 (17.6-190.8), and 112.4 (19.7-205.0) minutes. Injection site reactions or bruising were observed in 1 (4%) and 11 (41%) patients, respectively. Mild access-site haematomas occurred in 6 (22%), and severe access-site haematomas occurred in 2 patients (7%). No thrombocytopaenia was observed within 72 hours post dose.

Conclusions: In patients with STEMI, a single subcutaneous dose of RUC-4 at 0.075, 0.090, and 0.110 mg/kg showed dose-response high-grade inhibition of platelet function within 15 minutes.

Original languageEnglish
Pages (from-to)401-410
Number of pages73
JournalEurointervention
Volume17
Issue number5
DOIs
Publication statusPublished - Aug 2021

Keywords

  • 2017 ESC
  • ANTIPLATELET THERAPY
  • IMPACT
  • PERCUTANEOUS CORONARY INTERVENTION
  • PREHOSPITAL INITIATION
  • PRIMARY ANGIOPLASTY
  • STEMI
  • THROMBOCYTOPENIA
  • TICAGRELOR
  • TIROFIBAN
  • adjunctive pharmacotherapy
  • clinical research
  • clinical trials
  • innovation
  • ALPHA-IIB-BETA-3 ANTAGONIST

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