Clinical trial NCT06679998: A Phase I Clinical Trial Evaluating the Safety, Tolerability and Pharmacokinetics of AAPB for Injection
Official title: 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.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Acute Ischemic Stroke (AIS)
Lead sponsor: Jiangsu Kanion Pharmaceutical Co., Ltd
Sponsor class: INDUSTRY
First posted: 2024-11-08
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse event
timeFrame: 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 outcomes:
measure: Serum Human chorionic gonadotropin in female subjects of reproductive age
timeFrame: Screening period (day-14 ~ day-1)，Baseline Period (day0)，Final follow-up period(day3/day8)
measure: Maximum plasma concentration (Cmax)
timeFrame: Day1~day2
measure: Time to maximum plasma concentration (Tmax)
timeFrame: Day1-day2
measure: Elimination half-life (t1/2)
timeFrame: Day1-day2
measure: clearance, CL
timeFrame: Day1-day2
measure: Apparent distribution volume (Vz)
timeFrame: Day1-day2
measure: Steady statetime time to maximum plasma concentration （Tmax_ss）
timeFrame: Day1-day2， Day4-day8
measure: steady state minimal concentration（Cmin,ss）
timeFrame: Day1-day2， Day4-day8
measure: steady state maximum concentration（Cmax,ss）
timeFrame: Day1-day2， Day4-day8
measure: Fluctuation Factor （DF）
timeFrame: Day1-day2， Day4-day8
measure: steady state clearance（CLss）
timeFrame: Day1-day2， Day4-day8
measure: 12-lead electrocardiogram interpretation
timeFrame: Screening period (day-14 ~ day-1)，Baseline Period (day0)，Administration observation period (day1~3 /day1~8)， Final follow-up period(day3/day8)
measure: Blood pressure
timeFrame: Screening period (day-14 ~ day-1)，Baseline Period (day0)，Administration observation period (day1~3 /day1~8)， Final follow-up period(day3/day8)
measure: Respiration
timeFrame: Screening period (day-14 ~ day-1)，Baseline Period (day0)，Administration observation period (day1~3 /day1~8)， Final follow-up period(day3/day8)
measure: Heart rate
timeFrame: Screening period (day-14 ~ day-1)，Baseline Period (day0)，Administration observation period (day1~3 /day1~8)， Final follow-up period(day3/day8)
measure: Temperature
timeFrame: Screening period (day-14 ~ day-1)，Baseline Period (day0)，Administration observation period (day1~3 /day1~8)， Final follow-up period(day3/day8)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
Study officials:
affiliation: Beijing Tiantan Hospital
name: Li shuya Director of Clinical Trial Center
role: PRINCIPAL_INVESTIGATOR
References: