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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Web of Science)


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 AND RESULTS : In this double-blind, randomized study of 345 patients with CCS on background oral antiplatelet therapy, subcutaneous selatogrel (8 mg, n = 114; or 16 mg, n = 115) was compared with placebo (n = 116) ( 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
Article numberehz807
Pages (from-to)3132-3140
Number of pages9
JournalEuropean Heart Journal
Issue number33
Early online date14 Nov 2019
Publication statusPublished - 1 Sep 2020


  • Selatogrel
  • Platelet aggregation
  • Coronary artery disease
  • P2Y(12) receptor antagonist
  • Pharmacodynamics
  • Pharmacokinetics
  • ACT-246475

Cite this