Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes

Robert F. Storey, Paul A. Gurbel, Jurrien ten Berg, Corine Bernaud, George D. Dangas, Jean Marie Frenoux, Diana A. Gorog, Abdel Hmissi, Vijay Kunadian, Stefan K. James, Jean Francois Tanguay, Henry Tran, Dietmar Trenk, Mike Ufer, Pim van der Harst, Arnoud W.J. Van't Hof, Dominick J. Angiolillo

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
9 Downloads (Pure)

Abstract

Aims To study the pharmacodynamics and pharmacokinetics of selatogrel, a novel P2Y12 receptor antagonist for subcutaneous administration, in patients with chronic coronary syndromes (CCS). Methods In this double-blind, randomized study of 345 patients with CCS on background oral antiplatelet therapy, subcuta- and results neous selatogrel (8 mg, n = 114; or 16 mg, n = 115) was compared with placebo (n = 116) (ClinicalTrials.gov: NCT03384966). Platelet aggregation was assessed over 24 h (VerifyNow assay) and 8 h (light transmittance aggregometry; LTA). Pharmacodynamic responders were defined as patients having P2Y12 reaction units (PRU) <100 at 30 min post-dose and lasting >_3 h. At 30 min post-dose, 89% of patients were responders to selatogrel 8 mg, 90% to selatogrel 16 mg, and 16% to placebo (P < 0.0001). PRU values (mean ± standard deviation) were 10 ± 25 (8 mg), 4 ± 10 (16 mg), and 163 ± 73 (placebo) at 15 min and remained <100 up to 8 h for both doses, returning to pre-dose or near pre-dose levels by 24 h post-dose. LTA data showed similarly rapid and potent inhibition of platelet aggregation. Selatogrel plasma concentrations peaked 30 min post-dose. Selatogrel was safe and well-tolerated with transient dyspnoea occurring overall in 7% (16/229) of patients (95% confidence interval: 4-11%). Conclusions Selatogrel was rapidly absorbed following subcutaneous administration in CCS patients, providing prompt, potent, and consistent platelet P2Y12 inhibition sustained for >_8 h and reversible within 24 h. Further studies of subcutaneous selatogrel are warranted in clinical scenarios where rapid platelet inhibition is desirable.

Original languageEnglish
Pages (from-to)3132-3140
Number of pages9
JournalEuropean Heart Journal
Volume41
Issue number33
Early online date14 Nov 2019
DOIs
Publication statusPublished - 1 Sept 2020

Keywords

  • Coronary artery disease
  • P2Y receptor antagonist
  • Pharmacodynamics
  • Pharmacokinetics
  • Platelet aggregation
  • Selatogrel

Fingerprint

Dive into the research topics of 'Pharmacodynamics, pharmacokinetics, and safety of single-dose subcutaneous administration of selatogrel, a novel P2Y12 receptor antagonist, in patients with chronic coronary syndromes'. Together they form a unique fingerprint.

Cite this