A Phase I Clinical Trial Evaluating the Safety, Tolerability and Pharmacokinetics of AAPB for Injection (AAPB)

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.

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke (AIS)
• Intervention / Treatment: Drug: Single dose, AAPB by injection, intravenous drip.; Other: Single dose, placebo, intravenous drip.; Drug: Multiple dosing, AAPB for injection, intravenous drip; Other: Multiple dosing, placebo, IV drip

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.

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhao binjiang Director of Clinical Research; Phone Number: +86 15300025287; Email: zbj0601@kanion.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Beijing Tiantan Hospital, Capital Medical University
      • Contact: Li shuya Director of the clinical Trial Center; Phone Number: +86 13601367028; Email: shuyali85@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single administration of-AAPB-10mg group; 10mg of AAPB for injection was administered as a single intravenous drip	Drug: Single 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.
Placebo Comparator: Single dose - placebo -10mg group; 10mg of placebo was administered as a single intravenous infusion	Other: Single 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.
Experimental: Single administration of -AAPB-25mg group; 25mg AAPB for injection.The drug was administered as a single intravenous drip	Drug: Single 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.
Placebo Comparator: Single dose - placebo -25mg group; 25mg of placebo was administered as a single intravenous infusion	Other: Single 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.
Experimental: Single administration of -AAPB-50mg group; 50mg AAPB for injection.The drug was administered as a single intravenous drip	Drug: Single 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.
Placebo Comparator: Single dose - placebo -50mg group; 50mg of placebo was administered as a single intravenous infusion	Other: Single 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.
Experimental: Single administration of -AAPB-75mg group; 75mg AAPB for injection.The drug was administered as a single intravenous drip	Drug: Single 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.
Placebo Comparator: Single dose - placebo -75mg group; 75mg of placebo was administered as a single intravenous infusion	Other: Single 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.
Experimental: Single administration of-AAPB-100mg group; 100mg AAPB for injection.The drug was administered as a single intravenous drip	Drug: Single 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.
Placebo Comparator: Single dose - placebo -100mg group; 100mg of placebo was administered as a single intravenous infusion	Other: Single 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.
Experimental: Multiple administration-AAPB-A group for injection; AAPB-A group dose for injection An intravenous drip. Once a day for 7 days	Drug: Multiple 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.
Placebo Comparator: Multiple dosing -Placebo-A group; Placebo, Group A dose, Intravenous infusion, Once a day for 7 days	Other: Multiple 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.
Experimental: Multiple administration-AAPB-B group for injection; AAPB-B group dose for injection An intravenous drip. Once a day for 7 days	Drug: Multiple 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.
Placebo Comparator: Multiple dosing -Placebo-B group; Placebo, Group B dose, Intravenous infusion, Once a day for 7 days	Other: Multiple 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.

Secondary Outcome Measures

Outcome Measure	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).	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)

Collaborators and Investigators

• Sponsor: Jiangsu Kanion Pharmaceutical Co., Ltd
• Investigators: Principal Investigator: Li shuya Director of Clinical Trial Center, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): November 14, 2024
• Primary Completion (Estimated): January 12, 2026
• Study Completion (Estimated): March 26, 2026

Study Registration Dates

• First Submitted: November 4, 2024
• First Submitted That Met QC Criteria: November 6, 2024
• First Posted (Estimated): November 8, 2024

Study Record Updates

• Last Update Posted (Estimated): November 8, 2024
• Last Update Submitted That Met QC Criteria: November 6, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: AAPB-Ⅰ-KY001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No