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This study is divided into two parts. The first part adopts a single-center, randomized, single-blind, placebo-controlled dose escalation trial design to investigate the safety, tolerability, pharmacokinetics (PK), and effects on the QTc interval in healthy subjects after a single administration of HRS-9190 for injection at doses of 3 times or 6 times the ED95.
The second part uses a single-center, open-label trial design to examine the safety, tolerability, PK, pharmacodynamics (PD), and reversal effect of neostigmine (in combination with atropine) after intravenous bolus injection and continuous intravenous infusion of the loading dose (2 times the ED95) of HRS-9190 under different anesthesia regimens.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A: Intravenous injection, 3×ED95 | Experimental |
| |
| Group B: Intravenous injection, 6×ED95 | Experimental |
| |
| Group C: 2×ED95 (intravenous bolus) + intravenous infusion | Experimental |
| |
| Group D: 2×ED95 (intravenous bolus) + intravenous infusion | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HRS-9190 | Drug | HRS-9190 |
|
| Measure | Description | Time Frame |
|---|---|---|
| The incidence and severity of adverse events | from ICF signing date to Day 7 | |
| Plasma histamine levels | 10 minutes before midazolam administration and 40 minutes after administration |
| Measure | Description | Time Frame |
|---|---|---|
| AUC0-t of HRS-9190 | 0 hour to 8 hour after administration | |
| AUC0 inf of HRS-9190 | 0 hour to 8 hour after administration | |
| Cmax of HRS-9190 |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Third Xiangya Hospital of Central South University | Changsha | Hunan | 410013 | China |
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| 0 hour to 8 hour after administration |
| Tmax of HRS-9190 | 0 hour to 8 hour after administration |
| t1/2 of HRS-9190 | 0 hour to 8 hour after administration |
| CL of HRS-9190 | 0 hour to 8 hour after administration |
| λz of HRS-9190 | 0 hour to 8 hour after administration |
| VZ of HRS-9190 | 0 hour to 8 hour after administration |
| VSS of HRS-9190 | 0 hour to 8 hour after administration |
| MRTinf of HRS-9190 | 0 hour to 8 hour after administration |
| AUC%Extrap of HRS-9190 | 0 hour to 8 hour after administration |
| The C-QTc relationship of HRS-9190. | At least 90 minutes before the administration of midazolam to 24 hours after the administration of the investigational product |
| The maximum percentage of T1 suppression | 0 hour to about 1 hour after the end of infusion |
| Onset time | 0 hour to about 1 hour after the end of infusion |
| Duration of action | 0 hour to about 1 hour after the end of infusion |
| Recovery time | 0 hour to about 1 hour after the end of infusion |
| Recovery index | 0 hour to about 1 hour after the end of infusion |