Key result
SHR2285 was well tolerated with mild adverse events (70.3% vs 66.7% in placebo) and no increased risk of bleeding when combined with dual antiplatelet therapy in healthy subjects.
Why the study?
To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of SHR2285, an oral FXIa inhibitor, combined with aspirin, clopidogrel, or ticagrelor in healthy subjects.
Does SHR2285 combined with dual antiplatelet therapy have acceptable safety, tolerability, and pharmacodynamic efficacy in healthy subjects?
RCT (n=52)
Double-blind
RTSM via SAS software (1:3 or 2:3 ratio)
No
Does SHR2285 combined with dual antiplatelet therapy have acceptable safety, tolerability, and pharmacodynamic efficacy in healthy subjects?
SHR2285, a novel oral FXIa inhibitor, demonstrated a favorable safety profile and predictable pharmacodynamics when combined with dual antiplatelet therapy in healthy subjects, supporting further clinical development.
Supports evaluation in patients on DAPT; extends FXIa inhibitor safety data from healthy subjects.
Purpose: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of SHR2285, the first oral coagulation factor XIa (FXIa) inhibitor developed in China in combination with aspirin, clopidogrel or ticagrelor in healthy subjects. Methods: This study was a single-center, randomized, double-blind, placebo-controlled (only SHR2285) design (NCT04945616). A total of 52 healthy subjects, 29 male and 23 female, were completed in this study. The subjects were divided into three groups: A, B and C, 16 subjects in group A [aspirin + clopidogrel + placebo or SHR2285 200 mg bid (1:3, 4 received placebo and 12 received SHR2285)] 16 subjects in group B [aspirin + clopidogrel + placebo or SHR2285 300 mg bid (1:3, 3 received placebo and 13 received SHR2285)] and 20 subjects in group C (aspirin + ticagrelor + placebo or SHR2285 300 mg bid (2:3, 8 received placebo and 12 received SHR2285)), respectively. All groups were administered orally for six consecutive days. Safety, tolerability, pharmacokinetics and pharmacodynamics parameters were assessed. Results: 1) SHR2285 was well tolerated, and all adverse events were mild. There was no evidence of an increased risk of bleeding. 2) After 6 days of twice-daily administration, SHR2285 could reach a steady state. The mean half-life of SHR2285 in group A, group B and group C was 13.9 h, 14.5 h and 13.8 h, respectively. 3) SHR2285 markedly inhibited FXI activity and prolonged activated partial thromboplastin time (APTT). In group A, group B and group C, the mean maximum inhibition rate of FXI activity was 84.8%, 89.3% and 92.2% and the mean maximum prolongation of APTT was 2.08-fold, 2.36-fold and 2.26-fold, respectively. Conclusion: These data suggest that SHR2285, a potential oral FXIa inhibitor, is expected to become a novel, safe and effective anticoagulant when combined with aspirin, clopidogrel or ticagrelor.
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Ma et al. (2022) conducted an RCT in Healthy subjects (n=52). SHR2285 vs. Placebo was evaluated on Incidence of treatment-emergent adverse events (TEAEs). SHR2285 was well tolerated with mild adverse events (70.3% vs 66.7% in placebo) and no increased risk of bleeding when combined with dual antiplatelet therapy in healthy subjects.
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