Clinical trial NCT06570655: The Study of Pharmacokinetics and Pharmacodynamics of Huperzine a Injection in Healthy Chinese Subjects
Official title: The Study of Pharmacokinetics and Pharmacodynamics of Huperzine a Injection in Healthy Chinese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Subjects
Lead sponsor: Wanbangde Pharmaceutical Group Co., LTD
Sponsor class: INDUSTRY
Collaborators: name: Zhejiang Hospital
First posted: 2024-08-26
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The study used a single-center, open, sequential single-dose design. To evaluate the pharmacokinetics and dose-exposure relationship of huperzine A injection

Detailed description: The study was divided into four modes of administration. Administration method of A: intravenous injection (non-blood collection arm), intravenous injection of 0.2mg huperzine A injection. B, C, D Administration methods: 0.1mg, 0.2mg, 0.4mg huperzine A injection was injected intramuscularly into the deltoid muscle of the upper arm (the arm on the non-blood collection side). In each cycle, after fasting for at least 10 hours, the subjects received different dosing regimens according to A sequential single dosing method, that is, each subject received dosing method A first, followed by dosing method B after the cleaning period, dosing method C after the cleaning period, and dosing method D after the cleaning period. The wash-out period between the two doses was 7 days for each subject. To evaluate the pharmacokinetics and dose-exposure relationship of huperzine A injection.

Eligibility criteria: Inclusion Criteria:

1. The subject voluntarily confirms his or her willingness to participate in a particular trial and signed the written informed consent, after having been informed of all aspects of the trial that are relevant to the subject\&#39;s decision to participate.They were fully aware of the adverse reactions and voluntarily signed the written informed consent.
2. The subjects were able to communicate well with the investigators and complete the trial in accordance with the protocol;
3. Gender: Chinese male or female;
4. Age: 18-45 years old (including boundary value);
5. Body mass index (BMI) 19.0-26.0 kg/m2 \[BMI = weight/height 2 (kg/m2)\] (including boundary values), body weight ≥50kg for men and ≥45kg for women.

Exclusion Criteria:

1. Allergic history to huperzine A or any of its components; Patients with a history of allergy to two or more drugs or foods;
2. patients who have the following clinically significant diseases at present, including but not limited to diseases of the respiratory system, circulatory system, digestive system, blood system, endocrine system, immune system, skin system, mental nervous system, ENT and other related diseases;
3. existing or suspected existing epilepsy, angina pectoris, bronchial asthma, mechanical intestinal obstruction, renal insufficiency, urinary obstruction;
4. underwent major surgical procedures within 6 months before screening or planned to undergo surgical procedures during the trial;
5. if the vital signs, physical examination, electrocardiogram and laboratory findings are clinically significant;
6. patients with a history of hepatitis B, hepatitis C, AIDS, syphilis and/or clinically significant abnormalities in one or more of the four hemodialysis tests;
7. those who had lost blood within 3 months before screening (except physiological blood loss in women) or donated blood ≥200mL or donated blood components (such as plasma, platelets, peripheral blood stem cells, etc.) within 3 months;
8. use of any drugs that alter liver enzyme activity within 30 days before screening (e.g., inductors-barbiturates, carbamazepine, phenytoin, dexamethasone, etc.; \&#34;Inhibitors - SSRI antidepressants, ciprofloxacin, diltiazem, macrolides, metronidazole, ketoconazole, verapamil.

   Rice, fluoroquinolones);
9. patients who had used any drugs (including prescription drugs, over-the-counter drugs, Chinese herbal medicine) and health products within 14 days before screening, except topical drugs and eye drops;
10. vaccinated within 1 month before screening or during the planned trial period and within 1 month after the end of the trial;
11. participants who participated in a clinical trial and took a drug within 3 months before screening;
12. had a history of drug abuse within 5 years, and/or used drugs within 3 months before screening, and/or had a history of drug dependence, including herbal medicine, or screened positive for drug abuse;
13. smokers or those who did not agree to avoid using any tobacco products 48 hours before administration and during hospitalization, or who screened positive for nicotine at the first admission;
14. Regular drinkers in the preceding 6 months, defined as consuming more than 14 units of alcohol per week (1 unit =360mL of 5% beer or 45mL of 40% spirits or 150mL of 12% wine), Or did not agree to stop alcohol intake 48 hours before administration and during hospitalization, or had a positive breath alcohol test at first admission;
15. subjects who consumed excessive amounts of tea, coffee and/or caffeinated beverages (\&gt; 8 cups, 1 cup =250mL) per day before screening or disagreed with the prohibition of tea, coffee and/or caffeinated beverages 48 hours before drug administration and during hospitalization Or caffeinated foods, grapefruit (grapefruit) and/or grapefruit juice (grapefruit juice), and/or products containing poppy;
16. have a fertility plan (including sperm and egg donation plans) and/or do not agree to use an effective contraceptive method (non-drug during the trial) from the time of signing the informed consent until 3 months after the last dose of medication.

    Of;
17. difficulty in venous blood collection (unable to tolerate venipuncture, with a history of dizzy with needles and blood, poor vascular conditions, etc.);
18. subjects may not be able to complete the study for other reasons or should not be included according to the investigator\&#39;s opinion.

    In addition to the above requirements, female subjects who meet the following conditions should also be excluded:
19. pregnant or lactating women or those with a positive pregnancy test;
20. who used oral contraceptives within 30 days before screening;
21. using long-acting estrogen and/or progestin injections and/or implants within 6 months before screening;
22. had unprotected sex with a partner within 14 days before screening.

Primary outcomes:
measure: Pharmacokinetics (PK): Maximum blood concentration of Huperzine A(Cmax)
timeFrame: Day1、Day8、Day15、Day22
measure: PK: Area under the Huperzine A blood concentration-time curve from 0min to the time of last concentration(AUC0-t)
timeFrame: Day1、Day8、Day15、Day22
measure: PK：Area under the Huperzine A blood concentration-time curve from 0min to the infinity time (AUC0-∞)
timeFrame: Day1、Day8、Day15、Day22
Secondary outcomes:
measure: PD: maximum efficacy(Emax)
timeFrame: Day1、Day8、Day15、Day22
measure: PD: Area under the efficacy curve(AUEC)
timeFrame: Day1、Day8、Day15、Day22
measure: PD: Time to reach maximum efficacy(Tmax)
timeFrame: Day1、Day8、Day15、Day22
measure: PK: Time to peak maximum concentration of the Huperzine A(Tmax)
timeFrame: Day1、Day8、Day15、Day22
measure: PK: half life of Huperzine A(t1/2)
timeFrame: Day1、Day8、Day15、Day22
measure: PK: λz
timeFrame: Day1、Day8、Day15、Day22
measure: PK: Area under the curve(AUC_%Extrap)
timeFrame: Day1、Day8、Day15、Day22
measure: PK: Clearance(CL)
timeFrame: Day1、Day8、Day15、Day22
measure: PK：Apparent volume of distribution(Vd)
timeFrame: Day1、Day8、Day15、Day22
measure: PK：Bioavailability(F)
timeFrame: Day1、Day8、Day15、Day22
measure: Urine excretion of Huperzine A.(UE)
timeFrame: Baseline、Day15-Day17
measure: Cumulative urinary excretion of Huperzine A(CUE)
timeFrame: Baseline、Day15-Day17
measure: Urine excretion rate(UER)
timeFrame: Baseline、Day15-Day17
measure: Cumulative urinary excretion rate(CUER)
timeFrame: Baseline、Day15-Day17
measure: Faeces excretion(FE)
timeFrame: Baseline、Day15-Day17
measure: Faeces excretion rate(FER)
timeFrame: Baseline、Day15-Day17
measure: Metabolites of Huperzine A
timeFrame: Day15、Day22
measure: Number of participants with adverse events (AEs) or serious adverse events (SAEs) as assessed by NCI-CTCAE v5.0.
timeFrame: Day1-Day28
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: Clinical trial institution of the Zhejiang Xiaoshan hospital
state: China/Zhejiang
Study officials:
References: