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.

Purpose: To evaluate the safety, tolerability, pharmacokinetics and immunogenicity of DS002 injection, an anti-nerve growth factor (anti-NGF) monoclonal antibody for treating pain conditions, in healthy Chinese subjects.Methods: This study was a single-center, randomized, double-blind, single-dose escalation, placebo-controlled design (CTR20210155). A total of 53 healthy subjects, 27 male and 26 female, were enrolled in this study, and one subject withdrew from the study before administration. Seven dose groups were set up, which were 0.5 mg, 1.0 mg, 2.0 mg, 4.0 mg, 7.0 mg, 12.0 mg and 20.0 mg, respectively. The drug was administered by single subcutaneous injection. Four subjects were enrolled in the first dose group (0.5 mg) received DS002. Other dose groups enrolled eight subjects each, six of whom received DS002 while the other two received a placebo. Safety, tolerability, pharmacokinetic parameters and immunogenicity of DS002 were assessed.Results: DS002 was well tolerated; all adverse events were Grade 1–2, and did not reach the termination standard of dose increment within the range of 0.5–20.0 mg. Adverse event rates were generally similar across treatments. After a single subcutaneous injection, the median Tmax in different dose groups ranged 167.77–337.38 h; mean t1/2 ranged 176.80–294.23 h, the volume of distribution (Vz) ranged 5265.42–7212.00 ml, and the clearance rate (CL) ranged 12.69–24.75 ml/h. In the dose range of 0.5–20.0 mg, Cmax ranged from 51.83 ± 22.74 ng/ml to 2048.86 ± 564.78 ng/ml, AUC0-t ranged from 20615.16 ± 5698.28 h·ng/mL to 1669608.11 ± 387246.36 h·ng/mL, and AUC0-inf ranged from 21852.45 ± 5920.21 h·ng/mL to 1673504.66 ± 389106.13 h·ng/mL. They all increased with dose escalation, and Cmax and AUC0-t did not have a significant dose-linear relationship, whilst AUC0-t was not dose-dependent at all. anti-drug antibody test results of each group of all subjects in this trial were negative.Conclusion: DS002 showed satisfactory safety within the dose range of 0.5 mg–20.0 mg. The absorption and metabolism of DS002 were slow, it exhibited a low volume of distribution and the clearance rate was low. These data suggest that DS002, by blocking nerve growth factor, is expected to become a novel, safe and non-addictive treatment for pain conditions.

Aim: 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. A total of 52 healthy subjects, 29 male and 23 female, were enrolled in this study. The subjects were divided into three groups: A, B and C, 16 subjects in group A (aspirin+clopidogrel+placebo or SHR2285 200mg bid (1:3)), 16 subjects in group B (aspirin+clopidogrel+placebo or SHR2285 300mg bid (1:3)) and 20 subjects in group C (aspirin+ticagrelor+placebo or SHR2285 300mg bid (2:3)), respectively. All groups were administered orally for 6 consecutive days. 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 half-life of SHR2285 was 13.9h, 14.5h and 13.8h respectively. 3. SHR2285 markedly inhibited FXI: C and prolonged APTT. The maximum inhibition rates of FXI: C in the three groups were 84.8%, 89.3% and 92.2% and the maximum prolongation time of APTT was 2.08-, 2.36-, and 2.26-fold, respectively. 4. The combination of aspirin, clopidogrel or ticagrelor had limited effect on the AUC of SHR2285. Conclusion: These data suggest that SHR2285, a potential oral FXIa inhibitor, is expected to become a novel, safe and effective anticoagulant.

This was a single‐dose, randomized, open‐label, 2‐period crossover study to evaluate the bioequivalence of the ACC008 (test formulation [T]) versus coadministered ainuovirine (ANV) 150 mg, lamivudine (3TC) 300 mg, and tenofovir disoproxil fumarate 300 mg (reference formulation [R]) in the fasted state among the Chinese healthy adults. Eligible subjects were randomized into 2 cohorts to received treatment in 1 of 2 sequences (T → R, R → T). PK samples were collected from 1 hour before dosing to 144 hours after dosing in each period. The concentrations of ANV, 3TC, and tenofovir in plasma were determined by liquid chromatography–tandem mass spectrometry. Phoenix WinNonlin software was used for pharmacokinetic parameter calculation and bioequivalence evaluation. All the 90% confidence intervals of maximum concentration, area under the concentration–time curve from time zero to the last detectable time, and area under the concentration–time curve from time zero to infinity fell within the bioequivalence range. The safety was comparable between the 2 treatments, with no Grade III/VI or serious adverse events. ACC008 was bioequivalent to administration of its individual components, including ANV 150 mg, 3TC 300 mg, and tenofovir disoproxil fumarate 300 mg with favorable safety profile.