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TQD3606 is a fixed-dose combination of meropenem and avibatam. This study is a phase I clinical study to evaluate the safety, tolerability and pharmacokinetic characteristics of TQD3606 injection in a single center, randomized, double-blind, placebo-controlled, single and multiple administration in healthy subjects, and to explore the excretion of TQD3606 in urine. To evaluate the tolerability and safety of injectable TQD3606 after single and multiple dosing in healthy subjects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| The injectable TQD3606 | Experimental | received a single dose of 0.75g TQD3606 for injection |
|
| The injectable TQD3606+ meropenem | Active Comparator | First, a single dose of 0.5g of meropenem for injection was administered for 0.5h intravenous infusion; after washout for at least 2 days, 0.75g of TQD3606 for injection was administered for 1h intravenous infusion; for at least 2 days of washout, 0.75g was administered A single dose of TQD3606 for injection was administered for 2 hours, and the elution time was at least 2 days. Finally, a single dose of 0.75 g of TQD3606 for injection was administered, and the duration of intravenous infusion was 3 hours. |
|
| The injectable TQD3606+ meropenem+ Avibactam Sodium | Active Comparator | According to the random table, they were divided into two groups, A and B, Group A was given 1.0g meropenem for injection (Mepin) in the first cycle, and 0.5g avibactam sodium for injection in the second cycle. The third cycle was given 1.5g TQD3606 for injection; group B was given 0.5g avibactam sodium for injection in the first cycle, 1.0g meropenem (Mepin) for injection in the second cycle, and 1.5g for injection in the third cycle TQD3606. |
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| The injectable TQD3606-1 | Experimental | First, 0.75g TQD3606 for injection was administered multiple times (Dosing every 8 hours, 3 consecutive doses), and at least 2 days were washed out after the last dose; then 1.125g TQD3606 for injection was administered multiple times (Dosing every 12 hours, 2 consecutive doses) times), wash out at least 2 days after the last administration; finally, a single administration of 2.25 g of TQD3606 for injection (Dosing every 12 hours, once administered). Intravenous infusion for 3 hours. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| The injectable TQD3606 | Drug | TQD3606 is a fixed-dose combination of meropenem and avibatam. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Concentration (Cmax) | Maximum Concentration | 1 hour before administration,to 24 hours after administration. |
| Area under the plasma concentration-time curve from initial dosing to 24 hours (AUC0-24) | Area under the plasma concentration-time curve from initial dosing to 24 hours | 1 hour before administration,to 24 hours after administration. |
| Measure | Description | Time Frame |
|---|---|---|
| Time to maximum concentration following drug administration (Tmax) | Time to maximum concentration following drug administration | 1 hour before administration,to 24 hours after administration. |
| Apparent terminal elimination half-life following drug administration (t1/2) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Haimiao Yang, Master | Contact | 0431-86177635 | czfyyq728@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Affiliated Hospital of Changchun University of Traditional Chinese Medicine | Changchun | Jilin | 130103 | China |
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| ID | Term |
|---|---|
| D007239 | Infections |
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| ID | Term |
|---|---|
| D000077731 | Meropenem |
| ID | Term |
|---|---|
| D013845 | Thienamycins |
| D015780 | Carbapenems |
| D047090 | beta-Lactams |
| D007769 | Lactams |
| D000577 |
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| The injectable TQD3606/ Placebo | Placebo Comparator | First, a single dose of 3.0g TQD3606 for injection/placebo was administered, intravenous infusion for 3hours, and washout for at least 3 days; then multiple doses of 3.0g TQD3606 for injection/placebo were administered (Dosing every 8 hours, 10 consecutive doses) , the intravenous infusion duration is 3hours. |
|
| meropenem | Drug | Meropenem is a carbapenem antibiotic |
|
| Avibactam Sodium | Drug | Avibactam is beta-lactamase inhibitor. |
|
| Placebo | Drug | It is a placebo. |
|
Apparent terminal elimination half-life following drug administration |
| 1 hour before administration,to 24 hours after administration. |
| Area under plasma concentration-time curve from first dosing to last measurable concentration point (AUC0-t) | Area under plasma concentration-time curve from first dosing to last measurable concentration point | 1 hour before administration,to 24 hours after administration. |
| The amount of drug excreted through urine 24 hours after administration (Ae0-24) | The amount of drug excreted through urine 24 hours after administration | 1 hour before administration,to 24 hours after administration. |
| Cumulative excretion rate of drugs through urine | Cumulative excretion rate of drugs through urine | 1 hour before administration,to 24 hours after administration. |
| The total clearance (CLt) The total clearance (CLt) | The total clearance | 1 hour before administration,to 24 hours after administration. |
| Renal clearance (CLr) | Renal clearance | 1 hour before administration,to 24 hours after administration. |
| Elimination rate constant(λz) | Elimination rate constant | 1 hour before administration,to 24 hours after administration. |
| Apparent volume of distribution (Vd/F) | Apparent volume of distribution | 1 hour before administration,to 24 hours after administration. |
| Mean residence time (MRT) | Mean residence time | 1 hour before administration,to 24 hours after administration. |
| Valley concentration (Cmin,ss) | Valley concentration | Within 60 minutes before 8th to 10th administration and 24 hours after 10th administration |
| Accumulation index | Accumulation index | Within 60 minutes before 8th to 10th administration and 24 hours after 10th administration |
| Adverse event rate | The occurrence of all adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs). | Baseline up to 24 hours after administration |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 | Monitor the safety indicators of subjects during the trial | Baseline up to 24 hours after administration |
| Body temperature | Monitor the safety indicators of subjects during the trial | 1 hour before administration and 24 hours after administration |
| Pulse | Monitor the safety indicators of subjects during the trial | 1 hour before administration and 24 hours after administration |
| Systolic and diastolic blood pressure | Monitor the safety indicators of subjects during the trial | 1 hour before administration and 24 hours after administration |
| Number of participants with abnormal laboratory test results | Monitor the safety indicators of subjects during the trial | Baseline up to 24 hours after administration |
| Amides |
| D009930 | Organic Chemicals |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |