Pharmacokinetics of Huperzine A Oral Solution in Healthy Participants

A Single-Center, Randomized, Double-Blind, Multiple-Dose, Dose-Escalation Study to Evaluate the Pharmacokinetics of Huperzine A Oral Solution in Healthy Participants

In this study, 4 dose groups are planned: Group 1 (0.22 mg, QD), Group 2 (0.22 mg, BID), Group 3 (0.44 mg, QD), and Group 4 (0.44 mg, BID). Ten healthy study participants will be enrolled in each dose group, and randomized to the investigational drug group or the placebo group in a 4:1 ratio (i.e., 8 study participants in the investigational drug group and 2 study participants in the placebo group). An appropriate gender ratio will be ensured within each dose group.

Inclusion Criteria:

1. Participants must provide written informed consent prior to the study, with full understanding of the study's objectives, procedures, and potential adverse reactions;
2. Participants must be able to communicate effectively with the investigators and comply with the protocol requirements throughout the study.
3. Healthy male or female, aged 18 to 55 years (inclusive);
4. Body mass index (BMI) range: 19.0 to 26.0 kg/m2 [BMI = body weight/height2 (kg/m2)] (inclusive); male weight ≥50 kg, female weight ≥45 kg.

Exclusion Criteria:

1. History of allergy to huperzine A or any drug component (pharmaceutical-grade sodium benzoate); history of allergies to two or more drugs, foods, etc.;

2. History or suspected history of gastrointestinal bleeding, or conditions posing a risk of gastrointestinal bleeding (e.g., peptic ulcer, inflammatory bowel disease, diverticula, hemorrhoids, colonic polyps, etc.);

3. Currently diagnosed with or suspected of having epilepsy, angina pectoris, bronchial asthma, mechanical intestinal obstruction, renal insufficiency, or urinary tract obstruction;

4. Currently diagnosed with or suspected of having other serious diseases that, in the judgment of the investigator, make the individual unsuitable for participation in the study. These may include, but are not limited to, diseases related to the respiratory, circulatory, digestive, hematologic, endocrine, immune, integumentary, neuropsychiatric, or otorhinolaryngologic systems;

5. Underwent major surgery within 180 days prior to the first dose or plans to undergo surgery during the study period;

6. Participants with significant abnormalities in vital signs (normal reference ranges for vital signs (including critical values): body temperature (aural) 35.9 ℃ to 37.4 ℃, sitting systolic blood pressure 90 mmHg to 140 mmHg, sitting diastolic blood pressure 60 mmHg to 90 mmHg, sitting pulse 50 to 100 beats per minute, respiratory rate 12 to 20 breaths per minute), physical examination, electrocardiogram (QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 ms (males) or >460 ms (females)), or laboratory test results, and judged by the investigator as unsuitable for participation in this study;

7. History of hepatitis B, hepatitis C, HIV, or syphilis and/or those with one or more abnormal results in infectious disease screening (anti-HIV antibody, hepatitis B surface antigen, anti-hepatitis C virus antibody, anti-Treponema pallidum antibody) that are considered clinically significant by the investigator;

8. Study participants who have experienced blood loss (excluding normal physiological blood loss in females) or donated ≥200 mL of blood or donated blood components (e.g., plasma, platelets, peripheral blood stem cells, etc.) within 90 days prior to the first dose;

9. Individuals who used any drugs that alter hepatic enzyme activity within 30 days prior to the first dose (e.g., inducers such as barbiturates, carbamazepine, phenytoin sodium, dexamethasone; inhibitors such as selective serotonin reuptake inhibitors [SSRIs], ciprofloxacin, diltiazem, macrolides, metronidazole, ketoconazole, verapamil, fluoroquinolones, etc.), or non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., aspirin, ibuprofen, naproxen, etc.);

10. Use of any medications (including prescription drugs, over-the-counter drugs, and herbal medicines) and health supplements within 14 days prior to the first dose or within 5 half-lives of previous medication (whichever is longer), with the exception of topical medications and ophthalmic drops intended for local use.

11. Study participants who have been vaccinated within 30 days prior to the first dose or plan to be vaccinated within 30 days after the end of the study;

12. Participation in any clinical study within 90 days prior to the first dose;

13. History of drug abuse within 5 years prior to screening, and/or use of illicit drugs within 90 days prior to screening, and/or history of drug dependence, including herbal medicine, or positive urine drug screening;

14. Average daily smoking of more than 5 cigarettes within 90 days prior to screening, or unwillingness to avoid using any tobacco products within 48 h prior to the first dose and during hospitalization, or positive result in nicotine screening;

15. Regular alcohol consumption within 180 days prior to screening, defined as consuming more than 14 units of alcohol per week (1 unit of alcohol = 360 mL of beer or 45 mL of spirits or 150 mL of wine), or unwillingness to stop alcohol intake within 48 h prior to the first dose and during hospitalization, or positive result in alcohol breath test;

16. Excessive daily consumption of tea, coffee, and/or caffeine-containing beverages (more than 8 cups, 1 cup = 250 mL) within 90 days prior to screening, or unwillingness to abstain from tea, coffee, and/or caffeine-containing foods, grapefruit (pomelo) and/or grapefruit juice (pomelo juice), and/or poppy-containing products within 48 h prior to the first dose and during hospitalization;

17. Individuals who have plans for reproduction (including sperm or egg donation) from the time of signing the informed consent until 90 days after the last administration of the investigational product, and/or who do not agree to use effective non-pharmacological contraceptive methods during the study period;

18. Individuals unable to adhere to a standardized diet during the study or those with lactose intolerance (e.g., experiencing diarrhea after consuming milk);

19. Individuals with difficulty in venous blood collection (intolerance to venipuncture, history of needle or blood phobia, poor vascular condition, etc.);

20. Individuals who are otherwise unable to complete the study or are deemed unsuitable for inclusion by the investigator shall also be excluded.

    In addition to the aforementioned criteria, female participants meeting any of the following conditions shall also be excluded:

21. Currently pregnant or breastfeeding, or have a positive pregnancy test result;

22. Use of oral contraceptives within 30 days prior to the first dose;

23. Use of long-acting estrogen and/or progestin injections and/or implants within 180 days prior to the first dose;

24. Unprotected sexual intercourse with a partner within 14 days prior to the first dose.