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This is a single-center, Phase 1, placebo and positive-controlled, randomized, partial-blind, integrated, sequential ascending dose / multiple ascending dose study.The safety, tolerability, pharmacokinetics and pharmacodynamics of multiple continuous IV infusion ascending doses of HSK36273 in healthy volunteers will be evaluated.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HSK36273 | Experimental | Multiple continuous IV infusion ascending doses in cohort 1-5 |
|
| Placebo | Placebo Comparator | 5 cohorts with matching placebo to HSK36273 |
|
| Heparin sodium injection | Active Comparator | Cohort 1-2 with matching positive control to HSK36273 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HSK36273 | Drug | Multiple continuous IV infusion ascending doses for 5 days |
| |
| Measure | Description | Time Frame |
|---|---|---|
| The number and severity of treatment emergent adverse events (TEAEs) . | To assess the safety and tolerability of multiple of HSK36273 following 24-hour continuous IV infusions administered over 5 consecutive days with ascending doses in healthy subjects | Day1 to Day8 |
| Measure | Description | Time Frame |
|---|---|---|
| AUC0-24h | Area under the drug concentration-time curve, from time 0h to 24h | within 1 hour before administration until 24 hours after starting administration |
| AUC0-144h | Area under the drug concentration-time curve, from time 0h to 144h |
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Inclusion Criteria:
Adult males and females, 18 to 45 years of age (inclusive) at Screening.
Body Mass Index (BMI) ≥ 18.0 and ≤ 28.0 kg/m2 and a weight of at least 45 kg for female and 50 kg for male.
The subject must be willing and able to provide written informed consent
Medically healthy without clinically significant abnormalities at Screening and predose on Day 1, including:
Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
Willing and able to comply with all study evaluations and adhere to protocol schedules and constraints.
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| the Second Affiliated Hospital Zhejiang University School of Medicine | Hangzhou | Zhejiang | China |
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| ID | Term |
|---|---|
| D006493 | Heparin |
| ID | Term |
|---|---|
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |
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| Placebo |
| Drug |
Matching placebo |
|
| Heparin sodium injection | Drug | Matching positive control |
|
| within 1 hour before administration until 144 hours after administration |
| Css | Steady-State Concentration with a the Initiation of Continuous IV 5-day Infusion of HSK36273 | within 1 hour before administration until 144 hours after administration |
| Tss | Time to Reach a Steady-State Concentration Following a the Initiation of Continuous IV 5-day Infusion of HSK36273 | within 1 hour before administration until 144 hours after administration |
| t1/2 | Apparent terminal half-life | 24 hours after administration |
| CL | Apparent total clearance of drug | 24 hours after administration |
| Vd | Apparent volume of distribution | 24 hours after administration |
| Activated Partial Thromboplastin Time (aPTT) | Clotting Biomarker Activated Partial Thromboplastin Time During the Course of a Continuous IV 5-day Infusion of HSK36273 | within 1 hour before administration until 144 hours after administration |
| Prothrombin Time (PT) | Clotting Biomarker Prothrombin During the Course of a Continuous IV 5-day Infusion of HSK36273 | within 1 hour before administration until 144 hours after administration |
| Activated Clotting Time (ACT) | Clotting Biomarker Activated Clotting Time During the Course of a Continuous IV 5-day Infusion of HSK36273 | within 1 hour before administration until 144 hours after administration |
| FXIa | Change from baseline in factor XI activity | within 1 hour before administration until 144 hours after administration |