A Phase I Clinical Trial to Evaluate the Pharmacokinetic Characteristics of Ammoxetine Hydrochloride Enteric-Coated Tablets in Participants With Moderate Renal Impairment and Normal Renal Function

A Single-Center, Non-Randomized, Open-Label, Parallel-Group Phase I Clinical Trial to Evaluate the Pharmacokinetic Characteristics of Multiple Doses of Ammoxetine Hydrochloride Enteric-Coated Tablets in Participants With Moderate Renal Impairment and Normal Renal Function

This study is a single-center, non-randomized, open-label, parallel-group, multiple-dose Phase I clinical trial evaluating the pharmacokinetic characteristics of ammoxetine hydrochloride enteric-coated tablets in participants with normal renal function and moderate renal impairment. The study enrolls 16 participants divided into two groups: Group A (participants with normal renal function) and Group B (participants with moderate renal impairment). Participants in both groups receive 60 mg of ammoxetine hydrochloride enteric-coated tablets daily at 1 hour after meals, from day 1 to day 6. Blood samples for pharmacokinetic (PK) analysis, urine samples, and safety parameters are collected before and after dosing according to the trial protocol.

Inclusion Criteria:

Inclusion criteria for participants with abnormal liver function (all 7 criteria must be met):

1. Adults aged 18 ~ 75 years (inclusive), regardless of gender
2. Body weight ≥ 45.0 kg (female) or ≥ 50.0 kg (male), body mass index (BMI) in the range of 19 ~ 32 kg/m2 (inclusive);
3. Participants whose medical history, vital signs, physical examination, laboratory tests (hematology, blood biochemistry, urinalysis, coagulation function, infectious disease screening, and other relevant tests), Chest X-ray and other examination must be deemed suitable for participation in this study by the investigator;
4. Participants and their partners must use effective contraception (such as condoms or an intrauterine device) from 2 weeks prior to screening until 6 months after the end of the study, unless they have already undergone permanent sterilization procedures, such as bilateral tubal ligation or vasectomy; furthermore, they must not donate sperm or eggs.
5. Participants who voluntarily sign the informed consent form and agree to cooperate in completing the trial according to the protocol.

Exclusion Criteria:

Participants meeting any of the following criteria will be excluded from this trial:

All participants:

1. Individuals with a history of allergies (allergic to two or more drugs, foods, or pollens);

2. Individuals with major psychiatric disorders, neurological disorders, or other systemic diseases that the investigator deems may affect trial results;

3. Participants who have had a severe infection or trauma within 4 weeks prior to screening, or who have undergone surgery (e.g., gastrectomy) that may affect drug absorption, distribution, metabolism, or excretion, or who are scheduled for surgery or hospitalization for other reasons during the trial period;

4. Participants who have experienced any of the following cardiovascular or cerebrovascular events within 6 months prior to screening: severe/unstable angina, myocardial infarction, symptomatic congestive heart failure (NYHA Class II-IV), a history of clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, or left ventricular dysfunction; transient ischemic attack or cerebrovascular accident (e.g., stroke);history of coronary artery bypass grafting or coronary stenting, or other cardiovascular diseases, and who are deemed unsuitable for participation in this clinical trial by the investigator;

5. Participants who have participated in other drug clinical trials within 3 months prior to screening (as determined by the date of administration);

6. Smokers or heavy drinkers (consumption of 14 units of alcohol per week within 4 weeks prior to screening: 1 unit = 285 mL of beer, 25 mL of spirits, or 150 mL of wine; smoking ≥5 cigarettes per day) or those with a history of substance or drug abuse within the past year;

7. Individuals who have donated or lost more than 200 mL of blood within 8 weeks prior to screening;

8. Individuals with a positive breathalyzer test for alcohol or a positive urine test for drug abuse during the screening period;

9. Individuals who habitually consumed excessive amounts of caffeinated beverages or foods within 4 weeks prior to screening. Examples include coffee, tea, chocolate, cola, and Red Bull (daily caffeine intake should not exceed 6 units).1 caffeine unit = 1 cup of coffee (177.4 mL) = 2 cans of cola (354.9 mL) = 1 cup of tea (354.9 mL) = 1/2 cup of energy drink = 85 g of chocolate;

10. Participants who used strong or moderate inhibitors of liver enzymes (CYP2D6) within 4 weeks prior to screening;

11. Pregnant or breastfeeding women, or female participants who test positive for pregnancy during the screening period;

12. Participants with QTcF on a 12-lead ECG exceeding the upper limit of normal (>450 ms for males or >470 ms for females), or those with ECG findings deemed clinically significant by the study physician, history of arrhythmia, syncope related to arrhythmia, or those using of a cardiac pacemaker or other cardiac-related conditions. Note: Conditions include but are not limited to: heart failure; hypokalemia; atrial fibrillation, atrial flutter, atrial premature beats, ventricular premature beats, non-sustained or sustained ventricular tachycardia; bradycardia or sick sinus syndrome; personal or family history of any cardiac conduction abnormalities; personal or family history of long QT syndrome (LQTS); or family history of sudden death;

13. Individuals with orthostatic hypotension (a decrease in systolic blood pressure of 20 mmHg or diastolic blood pressure of 10 mmHg upon standing compared to the supine position);

14. Individuals with a history of dysphagia or any gastrointestinal disease affecting drug absorption;

15. Patients with concurrent viral infections (anti-HCV positive, anti-HIV positive, HBsAg positive) or concurrent syphilis infection;

16. Participants with CYP2D6 poor metabolizer;

17. Participants deemed by the investigator to be unsuitable for this clinical trial for other reasons.

    Participants with renal impairment:

18. Participants who have undergone a kidney transplant or who require hemodialysis during the study;

19. Participants with urinary tract obstruction or difficulty urinating, urinary incontinence, or anuria;

20. Participants with acute diseases affecting any organ other than the condition causing renal impairment, or those with chronic diseases that may affect the pharmacokinetics of the study drug (e.g., hepatic impairment), who are deemed unsuitable for this trial by the investigator;

21. Participants with coagulation abnormalities (INR > 1.5 or prothrombin time (PT) > ULN + 4 seconds or APTT > 1.5 × ULN), or a history of clinically significant bleeding within the 3 months prior to screening, or a clear predisposition to bleeding, such as gastrointestinal bleeding or hemorrhagic gastric ulcers, or current treatment with thrombolytic or anticoagulant therapy;

22. Participants with systolic blood pressure >160 mmHg and diastolic blood pressure >100 mmHg; pulse rate >100 bpm, during the time of screening;

23. Patients with acute hepatitis, chronic liver disease, or levels of ALT, AST, or GGT exceeding twice the upper limit of normal (ULN), or total bilirubin exceeding 1.5 times the ULN;

24. At screening, patients with gallbladder disease that is determined by the investigator to affect bile excretion;

25. Patients with a history of malignancy, psychiatric disorders, anxiety, or epilepsy;

    Participants with normal renal function:

26. Participants who have used any prescription drugs, over-the-counter medications, or traditional Chinese medicine (herbal medicines, proprietary Chinese medicines) within 2 weeks prior to screening.