Acute Ischemic Stroke (AIS)
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGSingle dose, AAPB by injection, intravenous drip.
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.
OTHERSingle dose, placebo, intravenous drip.
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.
DRUGMultiple dosing, AAPB for injection, intravenous drip
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.
OTHERMultiple dosing, placebo, IV drip
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.
Sponsors
Jiangsu Kanion Pharmaceutical Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy subjects, aged between 18 and 45 (both ends included), both male and female; 2. When screening patients, male weight ≥50kg, female weight ≥45kg, body mass index (BMI) in the range of 19-28 kg/m\^2 (including the upper and lower limits), BMI= weight (kg)/height (m) \^2; 3. Able to communicate well with researchers, willing and able to comply with the lifestyle restrictions specified in the program; 4. Women or men of reproductive age who agree to use investigatorial-approved contraceptive methods (such as Iuds, condoms, spermicide gel plus condoms, diaphragms, etc.) throughout the trial period; 5. Fully understand the purpose and requirements of the trial, voluntarily participate in the clinical trial and sign a written informed consent, and be able to complete the whole process of the trial according to the requirements of the trial.
Exclusion criteria
1. The investigator determines that the subject has a history of present disease and past disease or dysfunction affecting the clinical trial, including but not limited to diseases of the nervous system, cardiovascular system, respiratory system, digestive system, urinary system, endocrine system, metabolic disease, rheumatic disease, blood system, etc.; 2. Suffers from mental illness or has a history of mental illness; 3. Have a history of malignant tumors or other diseases that are not suitable for clinical trials; 4. History of cardiovascular disease (such as heart dysfunction, coronary artery disease, cardiomyopathy, valvular heart disease, family history of congenital long QT syndrome, family history of sudden death, etc.) or ECG results showing QTcF \> 450ms, or clinically significant conduction block or T wave changes; 5. Abnormal liver function (ALT, AST higher than the upper limit of normal reference value); 6. Any drugs that inhibit or induce liver drug metabolism enzymes (such as: inducers barbiturates, carbamazepine, phenytoin, glucocorticoids, omeprazole, etc.) were used within 30 days before drug administration; Inhibitors 5-hydroxyserotonin reuptake inhibitor (SSRI) antidepressants, cimetidine, Diltiazem, macrolides, nitroimidazoles, sedatives and hypnotics, verapamil, fluoroquinolones, antihistamines, etc. Or any prescription, over-the-counter, and herbal medicines other than those described above have been taken in the 14 days prior to drug administration; 7. Participated in any clinical trials within 3 months before enrollment; 8. Those who have special requirements for food and cannot comply with a unified diet; 9. People who consumed any caffeine-rich food or drink (coffee, tea, cola, chocolate, etc.) within 48 hours before the study drug administration, or who do not agree to prohibit the use of any caffeine-rich food or drink during the study period; 10. Known allergic history of test drug ingredients or similar drugs, allergic disease history or allergic constitution; 11. Smokers who smoked more than 10 cigarettes or equivalent cigarettes per day in the 1 year prior to screening, or those who could not comply with the prohibition of smoking during the test period; 12. Alcohol-addicted persons with an average weekly alcohol intake of more than 14 units (1 unit =285ml beer or 25ml spirits or 150ml wine) or positive for alcohol breath test in the year before screening; 13. Persons with a history of drug or drug abuse within the year prior to screening, or who test positive for drug abuse (screening items include: morphine, THC, methamphetamine, dimethylene dioxyamphetamine, ketamine and cocaine); 14. Complete physical examination, vital signs, laboratory examination, ECG examination determined by the investigator to be abnormal and clinically significant; 15. Hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), HIV antibody (HIV-AB), Treponema pallidum antibody (TP-Ab) any of the positive results; 16. Women who are pregnant or nursing, or who test positive for serum HCG before trial administration, or who are unable or unwilling to use investigator-approved contraception during the study period and for 3 months after the end of the study as directed by the investigator; 17. Study blood donation or blood loss ≥200ml within 3 months before drug administration, or have a history of blood product use; 18. Patients with a history of surgery within 3 months prior to study administration, or who have not recovered from surgery, or who have an anticipated surgical plan during the trial period; 19. Persons directly related to the clinical trial; 20. Patients who cannot tolerate venipunction and have a history of fainting needles and fainting blood; 21. Other subjects deemed unsuitable for this study by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse event | Simple ascending dose, follow-up visit from day 1 to day 3. Multiple Ascending Dose, follow-up visit from day 1 to day 8. | Incidence of Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration (Cmax) | Day1~day2 | 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). |
| Time to maximum plasma concentration (Tmax) | Day1-day2 | 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). |
| Elimination half-life (t1/2) | Day1-day2 | 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). |
| clearance, CL | Day1-day2 | 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). |
| Apparent distribution volume (Vz) | Day1-day2 | 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). |
| Steady statetime time to maximum plasma concentration （Tmax_ss） | Day1-day2， Day4-day8 | 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. |
| steady state minimal concentration（Cmin,ss） | Day1-day2， Day4-day8 | 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. |
| 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) | — |
| Fluctuation Factor （DF） | Day1-day2， Day4-day8 | 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. |
| steady state clearance（CLss） | Day1-day2， Day4-day8 | 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. |
| 12-lead electrocardiogram interpretation | Screening period (day-14 ~ day-1)，Baseline Period (day0)，Administration observation period (day1~3 /day1~8)， Final follow-up period(day3/day8) | Heart Rate，Cardiac rhythm， ECG RR interval，ECG QRS Interval， ECG PR Interval，ECG QTcF Interval， |
| Blood pressure | Screening period (day-14 ~ day-1)，Baseline Period (day0)，Administration observation period (day1~3 /day1~8)， Final follow-up period(day3/day8) | Blood pressure is recorded in millimeters of mercury |
| Respiration | Screening period (day-14 ~ day-1)，Baseline Period (day0)，Administration observation period (day1~3 /day1~8)， Final follow-up period(day3/day8) | The unit of recording is the number of breaths per minute. |
| Heart rate | Screening period (day-14 ~ day-1)，Baseline Period (day0)，Administration observation period (day1~3 /day1~8)， Final follow-up period(day3/day8) | The unit of heart rate is the number of heartbeats per minute. |
| Temperature | Screening period (day-14 ~ day-1)，Baseline Period (day0)，Administration observation period (day1~3 /day1~8)， Final follow-up period(day3/day8) | Body temperature is recorded in degrees Celsius |
| steady state maximum concentration（Cmax,ss） | Day1-day2， Day4-day8 | 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. |
Countries
China
Contacts
Primary ContactZhao binjiang Director of Clinical Research
Outcome results
None listed