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The trial used single-center, randomized, double-blind, placebo-controlled, single-dose ascending study.
The trial planned to enroll fifty-six healthy volunteers. The subjects were allocated to eight dose groups, including 0.5 mg (3+1), 1 mg (3+1), 2.5 mg (6+2), 5 mg (6+2), 10 mg (6+2), 20 mg (6+2), 35 mg(6+2) and 50 mg (6+2). Each dose group was allocated test drugs and placebos according to the proportion of subjects in the brackets mentioned above.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1:SYHA136 0.5 mg or Placebo matching SYHA136 0.5 mg | Experimental | Participants will receive a single oral dose of SYHA136 0.5 mg or Placebo matching SYHA136 0.5 mg under fasted conditions. |
|
| Cohort 2:SYHA136 1 mg or Placebo matching SYHA136 1 mg | Experimental | Participants will receive a single oral dose of SYHA136 1 mg or Placebo matching SYHA136 1 mg under fasted conditions. |
|
| Cohort 3:SYHA136 2.5 mg or Placebo matching SYHA136 2.5 mg | Experimental | Participants will receive a single oral dose of SYHA136 2.5 mg or Placebo matching SYHA136 2.5 mg under fasted conditions. |
|
| Cohort 4:SYHA136 5 mg or Placebo matching SYHA136 5 mg | Experimental | Participants will receive a single oral dose of SYHA136 5 mg or Placebo matching SYHA136 5 mg under fasted conditions. |
|
| Cohort 5:SYHA136 10 mg or Placebo matching SYHA136 10 mg | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SYHA136 0.5 mg | Drug | oral tablet |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events (AEs) | Number of participants that experience Adverse Events (AEs) | From Screening period to 12 Days Post dose |
| Serious Adverse Events (SAEs) | Number of participants that experience Serious Adverse Events (SAEs) | From Screening period to 12 Days Post dose |
| clinically significant laboratory assessment abnormalities | Number of participants with clinically significant laboratory assessment abnormalities | Up to 72 hours Post dose |
| clinically significant 12-lead electrocardiograms (ECGs) abnormalities | Number of participants with clinically significant 12-lead electrocardiograms (ECGs) abnormalities | Up to 72 hours Post dose |
| clinically significant physical examination abnormalities | Number of participants with clinically significant physical examination abnormalities | Up to 72 hours Post dose |
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the concentration-time curve from time zero to time of the Last Measurable Concentration (AUC0-tlast) | PK Assessment - Area Under the concentration-time curve from time zero to time of the Last Measurable Concentration (AUC0-tlast) | Up to 72 hours Post dose |
| Area under the concentration-time curve from time 0 to infinity (AUCinf) |
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Inclusion Criteria:
Exclusion Criteria:
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Participants will receive a single oral dose of SYHA136 10 mg or Placebo matching SYHA136 10 mg under fasted conditions.
|
| Cohort 6:SYHA136 20 mg or Placebo matching SYHA136 20 mg | Experimental | Participants will receive a single oral dose of SYHA136 20 mg or Placebo matching SYHA136 20 mg under fasted conditions. |
|
| Cohort 7:SYHA136 35 mg or Placebo matching SYHA136 35 mg | Experimental | Participants will receive a single oral dose of SYHA136 35 mg or Placebo matching SYHA136 35 mg under fasted conditions. |
|
| Cohort 1:SYHA136 50 mg or Placebo matching SYHA136 50 mg | Experimental | Participants will receive a single oral dose of SYHA136 50 mg or Placebo matching SYHA136 50 mg under fasted conditions. |
|
| SYHA136 1 mg |
| Drug |
oral tablet |
|
| SYHA136 2.5 mg | Drug | oral tablet |
|
| SYHA136 5 mg | Drug | oral tablet |
|
| SYHA136 10 mg | Drug | oral tablet |
|
| SYHA136 20 mg | Drug | oral tablet |
|
| SYHA136 35 mg | Drug | oral tablet |
|
| SYHA136 50 mg | Drug | oral tablet |
|
| Placebo matching SYHA136 0.5 mg | Drug | oral tablet |
|
| Placebo matching SYHA136 1 mg | Drug | oral tablet |
|
| Placebo matching SYHA136 2.5 mg | Drug | oral tablet |
|
| Placebo matching SYHA136 5 mg | Drug | oral tablet |
|
| Placebo matching SYHA136 10 mg | Drug | oral tablet |
|
| Placebo matching SYHA136 20 mg | Drug | oral tablet |
|
| Placebo matching SYHA136 35 mg | Drug | oral tablet |
|
| Placebo matching SYHA136 50 mg | Drug | oral tablet |
|
PK Assessment - Area under the concentration-time curve from time 0 to infinity (AUCinf) |
| Up to 72 hours Post dose |
| Maximum observed concentration (Cmax) | PK Assessment - Maximum observed concentration (Cmax) | Up to 72 hours Post dose |
| Time to reach maximum observed concentration (Tmax) | PK Assessment - Time to reach maximum observed concentration (Tmax) | Up to 72 hours Post dose |
| Terminal elimination half-life (t1/2) | PK Assessment - Terminal elimination half-life (t1/2) | Up to 72 hours Post dose |
| Apparent total body clearance (CL/F) | PK Assessment - Apparent total body clearance (CL/F) | Up to 72 hours Post dose |
| Apparent volume of distribution (Vz/F) | PK Assessment - Apparent volume of distribution (Vz/F) | Up to 72 hours Post dose |
| Amount of SYHA136 excreted in urine (Aeu) | PK Assessment - Amount of SYHA136 excreted in urine (Aeu) | Up to 72 hours Post dose |
| Renal clearance (CLr) | PK Assessment - Renal clearance (CLr) | Up to 72 hours Post dose |
| Activated Partial Thromboplastin Time(aPTT) | PD Assessment-Activated Partial Thromboplastin Time(aPTT) | Up to 48 hours Post dose |
| Fibrinogen(Fbg) | PD Assessment-Fibrinogen(Fbg) | Up to 48 hours Post dose |
| Thrombin Time(TT) | PD Assessment-Thrombin Time(TT) | Up to 48 hours Post dose |
| International Normalized Ratio(INR) | PD Assessment-International Normalized Ratio(INR) | Up to 48 hours Post dose |
| Anti-coagulation Factor Xa assays(AXA) | PD Assessment-Anti-coagulation Factor Xa assays(AXA) | Up to 48 hours Post dose |
| ID | Term |
|---|---|
| D020246 | Venous Thrombosis |
| ID | Term |
|---|---|
| D013927 | Thrombosis |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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