Healthy Participants, Participants With Mild Hepatic Impairment, Participants With Moderate Hepatic Impairment
Conditions
Brief summary
Use these resources to provide understandable information about this study to patients, families, and health care providers:This study is a multi-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 mild hepatic impairment (Child-Pugh Class A), moderate hepatic impairment (Child-Pugh Class B), and participants with normal liver function who are matched for age, weight, and gender. Participants in all groups receive 20 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, and safety parameters are collected before and after dosing according to the trial protocol.
Detailed description
Avoid duplicating information that will be entered or uploaded elsewhere in the record.
Interventions
Oral administration; 20 mg
Sponsors
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Drug: ammoxetine hydrochloride enteric-coated tablets .
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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, abdominal color Doppler ultrasound, electroencephalogram (EEG), alpha-fetoprotein (AFP), plasma ammonia, abnormal prothrombin, and other examination must be deemed suitable for participation in this study by the investigator; 4. Participants and their partners must use effective contraception (e.g., condoms, inert intrauterine devices, etc.) 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 must have not taken any medications within 2 weeks prior to screening, or must have been on a stable medication regimen for at least 4 weeks for the treatment of liver impairment and/or other comorbidities; 6. Participants who have mild or moderate hepatic impairment according to the Child-Pugh classification, resulting from chronic hepatic insufficiency or cirrhosis caused by a history of primary liver disease (e.g., viral hepatitis, alcoholic liver disease, autoimmune hepatitis, etc.), with the investigator determining that the patients liver function would remain stable for ≥1 month based on clinical presentation; 7. Participants who voluntarily sign the informed consent form and agree to cooperate in completing the trial according to the protocol. Inclusion criteria for participants with normal liver function (all 6 criteria must be met)： 1. Adults aged 18 \~ 75 years (inclusive), regardless of gender(matched for age and gender with the hepatic impairment group); 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, abdominal color Doppler ultrasound, and other examination must be deemed suitable for participation in this study by the investigator; 4. Participants and their partners must use effective contraception (e.g., condoms, inert intrauterine devices, etc.) 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 must have not taken any medications within 2 weeks prior to screening, or must have been on a stable medication regimen for at least 4 weeks for the treatment of other comorbidities; 6. 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: 1. Individuals with a history of allergies (allergic to two or more drugs, foods, or pollens); 2. Individuals with major psychiatric disorders, renal disease, neurological disorders, or other systemic diseases that the investigator deems may affect trial results; 3. 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); 4. Participants with a 12-lead ECG QTcF\>470 ms, or those with abnormal ECG findings that the study physician determines may influence the study results, or those with a history of severe arrhythmias, arrhythmia-related syncope, use of a cardiac pacemaker, or other cardiac-related conditions. Conditions include but are not limited to: heart failure; non-sustained or sustained ventricular tachycardia; sick sinus syndrome; or a family history of sudden death; 5. Smokers or heavy drinkers within 4 weeks prior to screening (consuming 14 units of alcohol per week: 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; 6. Individuals with a history of dysphagia or any gastrointestinal disease affecting drug absorption; 7. Participants with CYP2D6 poor metabolizer; 8. Individuals with a positive breathalyzer test for alcohol or a positive urine test for drug abuse during the screening period; 9. Individuals who have donated or lost more than 200 mL of blood within 8 weeks prior to screening; 10. Participants who have participated in other drug clinical trials within 3 months prior to screening (as determined by the date of administration); 11. 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; 12. Participants who used strong or moderate inhibitors of liver enzymes (CYP2D6) within 4 weeks prior to screening; 13. Individuals who have consumed dragon fruit, mango, pomelo, grapefruit, lime, star fruit, pomegranate, or foods or beverages prepared from these fruits within 7 days prior to screening; 14. Pregnant or breastfeeding women, or female participants who test positive for pregnancy during the screening period; 15. Individuals with estimated glomerular filtration rate (eGFR) \< 75 mL/min/1.73 m²calculated using the 2021 CKD-EPI formula based on serum creatinine levels during the screening period; 16. Participants with uncontrolled bacterial, viral, parasitic, or fungal infections requiring treatment at screening (excluding hepatitis B), or a history of severe active infection within 1 month prior to screening; 17. Participants deemed by the investigator to be unsuitable for this clinical trial for other reasons. Additional
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the concentration vs. time curve for one dosing interval at steady-state (AUCtau,ss) | Within 120 hours after the last dose |
| Maximum concentration observed during dosing interval at steady-state (Cmax,ss) | Within 120 hours after the last dose |
Secondary
| Measure | Time frame |
|---|---|
| The incidence of adverse events (AEs) | Up to 120 hours after the last dose |
| Minimum concentration observed during dosing interval at steady-state (Cmin,ss) | Up to 120 hours after the last dose |
| Half-Life (t1/2) | Up to 120 hours after the last dose |
| Mean concentration observed during dosing interval at steady-state (Cav,ss) | Up to 120 hours after the last dose |
| Plasma Maximum concentration (Cmax) | Within 24 hours after the first dose |
| Area under the concentration-time curve up to the last sampling point(AUClast) | Within 24 hours after the first dose |
| Accumulation index of AUC(RAUC) | Within 24 hours after the first dose |
Countries
China
Contacts
CONTACTClinical Trials Information Group officer
Outcome results
None listed