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

Publication ,  Journal Article
Bor, WL; Zheng, KL; Tavenier, AH; Gibson, CM; Granger, CB; Bentur, O; Lobatto, R; Postma, S; Coller, BS; van 't Hof, AWJ; Ten Berg, JM
Published in: EuroIntervention
August 6, 2021

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.

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Published In

EuroIntervention

DOI

EISSN

1969-6213

Publication Date

August 6, 2021

Volume

17

Issue

5

Start / End Page

e401 / e410

Location

France

Related Subject Headings

  • Treatment Outcome
  • ST Elevation Myocardial Infarction
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Platelet Function Tests
  • Platelet Aggregation Inhibitors
  • Percutaneous Coronary Intervention
  • Humans
  • 3201 Cardiovascular medicine and haematology
  • 0104 Statistics
 

Citation

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Bor, W. L., Zheng, K. L., Tavenier, A. H., Gibson, C. M., Granger, C. B., Bentur, O., … Ten Berg, J. M. (2021). Pharmacokinetics, pharmacodynamics, and tolerability of subcutaneous administration of a novel glycoprotein IIb/IIIa inhibitor, RUC-4, in patients with ST-segment elevation myocardial infarction. EuroIntervention, 17(5), e401–e410. https://doi.org/10.4244/EIJ-D-21-00287
Bor, Willem L., Kai L. Zheng, Anne H. Tavenier, C Michael Gibson, Christopher B. Granger, Ohad Bentur, Rita Lobatto, et al. “Pharmacokinetics, pharmacodynamics, and tolerability of subcutaneous administration of a novel glycoprotein IIb/IIIa inhibitor, RUC-4, in patients with ST-segment elevation myocardial infarction.EuroIntervention 17, no. 5 (August 6, 2021): e401–10. https://doi.org/10.4244/EIJ-D-21-00287.
Bor WL, Zheng KL, Tavenier AH, Gibson CM, Granger CB, Bentur O, Lobatto R, Postma S, Coller BS, van ’t Hof AWJ, Ten Berg JM. Pharmacokinetics, pharmacodynamics, and tolerability of subcutaneous administration of a novel glycoprotein IIb/IIIa inhibitor, RUC-4, in patients with ST-segment elevation myocardial infarction. EuroIntervention. 2021 Aug 6;17(5):e401–e410.

Published In

EuroIntervention

DOI

EISSN

1969-6213

Publication Date

August 6, 2021

Volume

17

Issue

5

Start / End Page

e401 / e410

Location

France

Related Subject Headings

  • Treatment Outcome
  • ST Elevation Myocardial Infarction
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Platelet Function Tests
  • Platelet Aggregation Inhibitors
  • Percutaneous Coronary Intervention
  • Humans
  • 3201 Cardiovascular medicine and haematology
  • 0104 Statistics