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

Официальное название

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.

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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.
• Другое 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.
• Препарат 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.
• Другое 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.

Первичные конечные точки

• Adverse event [Срок оценки: Simple ascending dose, follow-up visit from day 1 to day 3. Multiple Ascending Dose, follow-up visit from day 1 to day 8.]

Вторичные конечные точки (12)

• Serum Human chorionic gonadotropin in female subjects of reproductive age [Срок оценки: Screening period (day-14 ~ day-1)，Baseline Period (day0)，Final follow-up period(day3/day8)]
• Maximum plasma concentration (Cmax) [Срок оценки: Day1~day2]
• Time to maximum plasma concentration (Tmax) [Срок оценки: Day1-day2]
• Elimination half-life (t1/2) [Срок оценки: Day1-day2]
• clearance, CL [Срок оценки: Day1-day2]
• Apparent distribution volume (Vz) [Срок оценки: Day1-day2]
• Steady statetime time to maximum plasma concentration （Tmax_ss） [Срок оценки: Day1-day2， Day4-day8]
• steady state minimal concentration（Cmin,ss） [Срок оценки: Day1-day2， Day4-day8]
• steady state maximum concentration（Cmax,ss） [Срок оценки: Day1-day2， Day4-day8]
• Fluctuation Factor （DF） [Срок оценки: Day1-day2， Day4-day8]
• steady state clearance（CLss） [Срок оценки: Day1-day2， Day4-day8]
• 12-lead electrocardiogram interpretation [Срок оценки: Screening period (day-14 ~ day-1)，Baseline Period (day0)，Administration observation period (day1~3 /day1~8)， Final follow-up period(day3/day8)]

Критерии участия

Критерии включения

• Healthy subjects, aged between 18 and 45 (both ends included), both male and female;
• 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;
• Able to communicate well with researchers, willing and able to comply with the lifestyle restrictions specified in the program;
• 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;
• 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.

Критерии исключения

• 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.;
• Suffers from mental illness or has a history of mental illness;
• Have a history of malignant tumors or other diseases that are not suitable for clinical trials;
• 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;
• Abnormal liver function (ALT, AST higher than the upper limit of normal reference value);
• 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;
• Participated in any clinical trials within 3 months before enrollment;
• Those who have special requirements for food and cannot comply with a unified diet;
• 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;
• Known allergic history of test drug ingredients or similar drugs, allergic disease history or allergic constitution;
• 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;
• 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;
• 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);
• Complete physical examination, vital signs, laboratory examination, ECG examination determined by the investigator to be abnormal and clinically significant;
• Hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), HIV antibody (HIV-AB), Treponema pallidum antibody (TP-Ab) any of the positive results;
• 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;
• Study blood donation or blood loss ≥200ml within 3 months before drug administration, or have a history of blood product use;
• 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;
• Persons directly related to the clinical trial;
• Patients who cannot tolerate venipunction and have a history of fainting needles and fainting blood;
• Other subjects deemed unsuitable for this study by the investigator.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Beijing Tiantan Hospital, Capital Medical University — Пекин

Идентификаторы

NCT: NCT06679998 · AAPB-Ⅰ-KY001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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