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This is a Phase I clinical to evaluate the safety and tolerability of single and multiple intravenous infusions of AAPB at different doses over 7 consecutive days.
This is a dose-increasing, randomized, double-blind, placebo-controlled, single-dose/multiple-dose phase I clinical trial evaluating the safety, tolerability and pharmacokinetics of AAPB for injection in healthy Chinese subjects.
The objective of this study was to evaluate the safety, tolerability, and pharmacokinetic characteristics of single and multiple intravenous infusion of AAPB at different doses for 7 consecutive days, and to explore the metabolites and mass balance of AAPB for injection in vivo. It provides a research basis for exploring the efficacy and safety of AAPB for injection in the treatment of acute ischemic death.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single administration of-AAPB-10mg group | Experimental | 10mg of AAPB for injection was administered as a single intravenous drip |
|
| Single dose - placebo -10mg group | Placebo Comparator | 10mg of placebo was administered as a single intravenous infusion |
|
| Single administration of -AAPB-25mg group | Experimental | 25mg AAPB for injection.The drug was administered as a single intravenous drip |
|
| Single dose - placebo -25mg group | Placebo Comparator | 25mg of placebo was administered as a single intravenous infusion |
|
| Single administration of -AAPB-50mg group | Experimental | 50mg AAPB for injection.The drug was administered as a single intravenous drip |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Single dose, AAPB by injection, intravenous drip. | Drug | Subjects received a single intravenous infusion of AAPB for injection. Each dose of AAPB for injection was dissolved with 0.9% sodium chloride injection, the infusion volume was 100mL, once a day, and each time was continuously injected for 60 min±5min. |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse event | Incidence of Adverse Events | Simple ascending dose, follow-up visit from day 1 to day 3. Multiple Ascending Dose, follow-up visit from day 1 to day 8. |
| Measure | Description | Time Frame |
|---|---|---|
| Serum Human chorionic gonadotropin in female subjects of reproductive age | Screening period (day-14 ~ day-1),Baseline Period (day0),Final follow-up period(day3/day8) | |
| Maximum plasma concentration (Cmax) | Blood will be drawn from adult subjects pre-drug application(within 60min) and at 30min, 60min, 90min, 120min, 180min, 240min (4h), 480min (8h),720min (12h),1440min(24h). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zhao binjiang Director of Clinical Research | Contact | +86 15300025287 | zbj0601@kanion.com |
| Name | Affiliation | Role |
|---|---|---|
| Li shuya Director of Clinical Trial Center | Beijing Tiantan Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Beijing Tiantan Hospital, Capital Medical University | Beijing | Beijing Municipality | 100000 | China |
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| Single dose - placebo -50mg group |
| Placebo Comparator |
50mg of placebo was administered as a single intravenous infusion |
|
| Single administration of -AAPB-75mg group | Experimental | 75mg AAPB for injection.The drug was administered as a single intravenous drip |
|
| Single dose - placebo -75mg group | Placebo Comparator | 75mg of placebo was administered as a single intravenous infusion |
|
| Single administration of-AAPB-100mg group | Experimental | 100mg AAPB for injection.The drug was administered as a single intravenous drip |
|
| Single dose - placebo -100mg group | Placebo Comparator | 100mg of placebo was administered as a single intravenous infusion |
|
| Multiple administration-AAPB-A group for injection | Experimental | AAPB-A group dose for injection An intravenous drip. Once a day for 7 days |
|
| Multiple dosing -Placebo-A group | Placebo Comparator | Placebo, Group A dose, Intravenous infusion, Once a day for 7 days |
|
| Multiple administration-AAPB-B group for injection | Experimental | AAPB-B group dose for injection An intravenous drip. Once a day for 7 days |
|
| Multiple dosing -Placebo-B group | Placebo Comparator | Placebo, Group B dose, Intravenous infusion, Once a day for 7 days |
|
|
| Single dose, placebo, intravenous drip. | Other | Subjects received a single intravenous infusion of placebo. Each dose of placebo was dissolved by 0.9% sodium chloride injection with an infusion volume of 100mL once a day for 60 min±5min each time. |
|
| Multiple dosing, AAPB for injection, intravenous drip | Drug | Subjects received AAPB for injection with multiple intravenous drips. Each dose of AAPB for injection was dissolved with 0.9% sodium chloride injection, the infusion volume was 100mL, once a day, 60 min±5min each time, for 7 consecutive days. |
|
| Multiple dosing, placebo, IV drip | Other | Subjects received multiple intravenous doses of placebo. Each dose of placebo was dissolved by 0.9% sodium chloride injection with an infusion volume of 100mL once a day for 60 min±5min each time for 7 consecutive days. |
|
| Day1~day2 |
| Time to maximum plasma concentration (Tmax) | Blood will be drawn from adult subjects pre-drug application(within 60min) and at 30min, 60min, 90min, 120min, 180min, 240min (4h), 480min (8h),720min (12h),1440min(24h). | Day1-day2 |
| Elimination half-life (t1/2) | Blood will be drawn from adult subjects pre-drug application(within 60min) and at 30min, 60min, 90min, 120min, 180min, 240min (4h), 480min (8h),720min (12h),1440min(24h). | Day1-day2 |
| clearance, CL | Blood will be drawn from adult subjects pre-drug application(within 60min) and at 30min, 60min, 90min, 120min, 180min, 240min (4h), 480min (8h),720min (12h),1440min(24h). | Day1-day2 |
| Apparent distribution volume (Vz) | Blood will be drawn from adult subjects pre-drug application(within 60min) and at 30min, 60min, 90min, 120min, 180min, 240min (4h), 480min (8h),720min (12h),1440min(24h). | Day1-day2 |
| Steady statetime time to maximum plasma concentration (Tmax_ss) | Day1,blood will be drawn from adult subjects pre-drug application(within 60min) and at 30min, 60min, 80min, 100min, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h . Day4,5,6,7,blood will be drawn from adult subjects pre-drug application(within 15 min) . Day7, blood will be drawn from adult subjects pre-drug application 30min, 60min, 80min, 100min, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after administration. | Day1-day2, Day4-day8 |
| steady state minimal concentration(Cmin,ss) | Day1,blood will be drawn from adult subjects pre-drug application(within 60min) and at 30min, 60min, 80min, 100min, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h . Day4,5,6,7,blood will be drawn from adult subjects pre-drug application(within 15 min) . Day7, blood will be drawn from adult subjects pre-drug application 30min, 60min, 80min, 100min, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after administration. | Day1-day2, Day4-day8 |
| steady state maximum concentration(Cmax,ss) | Day1,blood will be drawn from adult subjects pre-drug application(within 60min) and at 30min, 60min, 80min, 100min, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h . Day4,5,6,7,blood will be drawn from adult subjects pre-drug application(within 15 min) . Day7, blood will be drawn from adult subjects pre-drug application 30min, 60min, 80min, 100min, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after administration. | Day1-day2, Day4-day8 |
| Fluctuation Factor (DF) | Day1,blood will be drawn from adult subjects pre-drug application(within 60min) and at 30min, 60min, 80min, 100min, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h . Day4,5,6,7,blood will be drawn from adult subjects pre-drug application(within 15 min) . Day7, blood will be drawn from adult subjects pre-drug application 30min, 60min, 80min, 100min, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after administration. | Day1-day2, Day4-day8 |
| steady state clearance(CLss) | Day1,blood will be drawn from adult subjects pre-drug application(within 60min) and at 30min, 60min, 80min, 100min, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h, 24h . Day4,5,6,7,blood will be drawn from adult subjects pre-drug application(within 15 min) . Day7, blood will be drawn from adult subjects pre-drug application 30min, 60min, 80min, 100min, 2h, 2.5h, 3h, 4h, 6h, 8h, 12h and 24h after administration. | Day1-day2, Day4-day8 |
| 12-lead electrocardiogram interpretation | Heart Rate,Cardiac rhythm, ECG RR interval,ECG QRS Interval, ECG PR Interval,ECG QTcF Interval, | Screening period (day-14 ~ day-1),Baseline Period (day0),Administration observation period (day1~3 /day1~8), Final follow-up period(day3/day8) |
| Blood pressure | Blood pressure is recorded in millimeters of mercury | Screening period (day-14 ~ day-1),Baseline Period (day0),Administration observation period (day1~3 /day1~8), Final follow-up period(day3/day8) |
| Respiration | The unit of recording is the number of breaths per minute. | Screening period (day-14 ~ day-1),Baseline Period (day0),Administration observation period (day1~3 /day1~8), Final follow-up period(day3/day8) |
| Heart rate | The unit of heart rate is the number of heartbeats per minute. | Screening period (day-14 ~ day-1),Baseline Period (day0),Administration observation period (day1~3 /day1~8), Final follow-up period(day3/day8) |
| Temperature | Body temperature is recorded in degrees Celsius | Screening period (day-14 ~ day-1),Baseline Period (day0),Administration observation period (day1~3 /day1~8), Final follow-up period(day3/day8) |
| ID | Term |
|---|---|
| D000083242 | Ischemic Stroke |
| ID | Term |
|---|---|
| D020521 | Stroke |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D007262 | Infusions, Intravenous |
| D007267 | Injections |
| ID | Term |
|---|---|
| D061605 | Administration, Intravenous |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D007263 | Infusions, Parenteral |
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