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

Abstract

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 and results In this double-blind, randomized study of 345 patients with CCS on background oral antiplatelet therapy, subcutaneous selatogrel (8\u2009mg, n\u2009=\u2009114; or 16\u2009mg, n\u2009=\u2009115) was compared with placebo (n\u2009=\u2009116) (ClinicalTrials.gov: NCT03384966). Platelet aggregation was assessed over 24\u2009h (VerifyNow assay) and 8\u2009h (light transmittance aggregometry; LTA). Pharmacodynamic responders were defined as patients having P2Y12 reaction units (PRU) <100 at 30 min post-dose and lasting ≥3\u2009h. At 30 min post-dose, 89% of patients were responders to selatogrel 8\u2009mg, 90% to selatogrel 16\u2009mg, and 16% to placebo (P\u2009<\u20090.0001). PRU values (mean ± standard deviation) were 10\u2009±\u200925 (8\u2009mg), 4\u2009±\u200910 (16\u2009mg), and 163\u2009±\u200973 (placebo) at 15 min and remained <100 up to 8\u2009h for both doses, returning to pre-dose or near pre-dose levels by 24\u2009h 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\u2009h and reversible within 24\u2009h. Further studies of subcutaneous selatogrel are warranted in clinical scenarios where rapid platelet inhibition is desirable.