Mild Hepatic Insufficiency, Moderate Hepatic Insufficiency, Normal Hepatic Function, Pharmacokinetic Differences, Saftey, Y-3
Conditions
Brief summary
The goal of this clinical trial is to assess the pharmacokinetic profiles and safety of Y-3 in subjects with mild hepatic insufficiency (Child-Pugh: grade A), moderate hepatic insufficiency (Child-Pugh: grade B) and gender, age, and weight matching normal hepatic function, so as to provide a scientific basis for rational clinical medication in patients with hepatic insufficiency. The main questions it aims to answer are: What the pharmacokinetic profiles of Y-3 (40 mg ) in subjects with mild hepatic insufficiency (Child-Pugh: grade A), moderate hepatic insufficiency (Child-Pugh: grade B) and gender, age, and weight matching normal hepatic function？ If drug Y-3 (40mg ) is safe and tolerate in subjects with mild hepatic insufficiency (Child-Pugh: grade A), moderate hepatic insufficiency (Child-Pugh: grade B) and gender, age, and weight matching normal hepatic function. Investigators will compare pharmacokinetic safety profiles of Y-3 (40 mg ) in subjects with different hepatic functions( mild hepatic insufficiency, moderate hepatic insufficiency, normal. Participants will: Take drug Y-3 (40 mg) only once. Answer questions regarding your medical history. Comply with the study procedures and requests. Complete all tests and collections of PK Sampling. Fasting for more than 10 hours before administration, water abstinence for 1 h before and after administration, and eating standard lunch and dinner 4 hours and 10 hours after starting administration. Must not use of nicotine-containing products (including nicotine patches). Must not do strenuous exercise for 1 hour before each clinical laboratory test blood draw. Subjects may engage in light recreational activities for the duration of the study. Follow your doctor's instructions, answer the investigator's questions about your health status truthfully, and cooperate with the test-related tests. During the experiment, the test should be completed in strict accordance with the requirements of the investigator, and the test-related work such as drug administration and sample collection should be conscientiously cooperated, and the research center should not leave the research center without authorization, and the rules and regulations of the research center and the investigator 's propaganda and education should be observed. Any medication taken should be reported truthfully. Must come to the hospital at the agreed follow-up time with the investigator and you. Inform the investigator or relevant person about any changes in your health status, including any favorable or unfavorable changes. Must not participate in any other drug clinical trials during this trial. Must tell your investigator about all medical treatments you plan to receive during the study, such as elective surgery or radiation therapy. In addition to yourself, at least one member of your family is expected to be aware of the clinical research you will be involved in and care about your health, and will be able to provide feedback to your doctor about your health during follow-up visits. Your family should promptly notify your study physician if you become seriously unwell, including hospitalization for treatment. Notify your investigator if your address, phone number, or other contact information changes. Must not use medications that may interfere with PK or safety.
Interventions
DRUGY-3 for injection（40mg）
The investigational drug (Y-3) consists of two parts: Y-3 for injection (lyophilized powder) and Solvent for Y-3 for injection (concentrated solution). Name: Y-3 for injection Strength: 20 mg Dosage Form: Lyophilized powder for injection Storage Condition: 2-8°C Supplier: Neurodawn Pharmaceutical Co., Ltd. Name: Reconstitution diluent for Y-3 for injection Strength: 3ml (containing 0.6 g propylene glycol) Dosage Form: Concentrated solution for injection Storage Condition: 2-8°C Supplier: Neurodawn Pharmaceutical Co., Ltd.
Sponsors
Neurodawn Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects must meet all of the following criteria for inclusion: 1. The subject fully understands the purpose and requirements of this trial, voluntarily participates in the clinical trial and signs a written ICF, strictly abide by the clinical study protocols and requirements to complete the whole study process; 2. Be 18\ 70 years old (including the boundary value) on the day of signing the ICF, both male and female; 3. At screening, the weight of male subjects ≥ 50kg, the weight of female subjects ≥ 45kg, and the body mass index \[BMI=Weight (kg)/height 2 (m2)\] within the range of 18.0\ 30.0kg/m2 (including boundary value); 4. Subjects (including their spouses or partners) have no sperm or egg donation programs, no fertility plans, and voluntary strict contraceptive use during the trial and within 3 months after the completion of the trial, see Appendix 1: Contraceptive measures administration and contraceptive requirements; 5. The estimated glomerular filtration rate (eGFR) calculated using the modification of diet in renal disease (MDRD) formula ≥ 80 ml/min/1.73 m2. (See Appendix 2: Glomerular Filtration Rate Calculation Formula); Subjects with hepatic insufficiency must also meet all of the following criteria: 6. Chronic liver injury caused by primary liver disease (such as hepatitis B, hepatitis C, autoimmune hepatitis, alcoholic liver disease, non-alcoholic liver disease, fatty liver, etc.) or clinical diagnosis of liver cirrhosis (see Appendix 3: Diagnostic Criteria for Liver Cirrhosis) caused by primary liver disease, Child-Pugh grade A or B patients with hepatic insufficiency (see Appendix 4: Liver Function Assessment for Child-Pugh classification), and have not used albumin within 14 days before screening, and the investigator judged that patients with mild hepatic insufficiency need to be clinically stable ≥for 28 days before taking the investigational products, and patients with moderate hepatic insufficiency need to be clinically ≥stable for 14 days before taking the investigational products, and the investigator judges that the subject's liver function status is stable from 2 weeks before screening to the end of the study, and no obvious deterioration will occur; 7. Have not taken any medication within 1 week before screening; or those who require long-term treatment for liver damage, complications and/or other concomitant diseases should have stable medication for at least 4 weeks (stable medication is judged by the investigator, except for drugs prohibited by the protocol). Subjects with normal liver function also need to meet all of the following criteria: 8. The demographic mean of subjects in the normal hepatic function group (Group C) at screening must meet the following matching standard: 1. Sex matching with liver insufficiency group (group A and group B), with a mean value of ±1 case; 2. Age matching with hepatic insufficiency group (Group A and Group B) with a mean ± 10 years; 3. Body weight matching with hepatic insufficiency group (group A and group B) with a mean of ±10%.
Exclusion criteria
* Subjects who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Cmax of Y-3 (40 mg ) in subjects with mild hepatic insufficiency , moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by venous blood and Phoenix WinNonlin | single-dose administration period (Day1-Day6) | Maximum observed plasma concentration. It was obtained directly from the measured plasma concentration-time data. |
| Evaluate the AUC 0-t of of Y-3 (40 mg ) in subjects with mild hepatic insufficiency , moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by venous blood and Phoenix WinNonlin. | single-dose administration period (Day1-Day6) | Area under the concentration-time curve from time 0 to the time of the last quantifiable concentration. Calculated according to linearity trapezoidal rule: AUC (i, i+1) = (Ti+1-Ti) (Ci+Ci+1) /2, and AUC0-t is the sum of all AUC (i, i + 1). |
| Evaluate the AUC 0-∞ of Y-3 (40 mg) in subjects with mild hepatic insufficiency , moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by venous blood and Phoenix WinNonlin. | single-dose administration period (Day1-Day6) | Area under the concentration-time curve from time 0 to infinity (extrapolated). AUC 0-∞ =AUC 0-t + Ct/λz (Ct is the last measured plasma concentration). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the AUC_%Extrap of Y-3 (40 mg ) in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by venous blood and Phoenix WinNonlin. | single-dose administration period (Day1-Day6) | The percentage of the AUC0-inf that has been extrapolated. AUC\_%Extrap = \[(AUC0-∞-AUC0-t)/AUC0-∞\] × 100% |
| Evaluate the Vz of Y-3 (40 mg) in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by venous blood and Phoenix WinNonlin. | single-dose administration period (Day1-Day6) | Volume of distribution. Vz = Div/AUC0-∞/λz |
| Evaluate the CL of Y-3 (40 mg) in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by venous blood and Phoenix WinNonlin. | single-dose administration period (Day1-Day6) | Total body clearance. CLz = Div /AUC0-∞ |
| Evaluate the MRT 0-t of Y-3 (40 mg) in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by venous blood and Phoenix WinNonlin. | single-dose administration period (Day1-Day6) | Mean residence time within the time from time zero to the lowest testing plasma concentration. MRT0-t = AUMC0-t/AUC0-t. |
| Evaluate the MRT 0-∞ of Y-3 (40 mg ) in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by venous blood and Phoenix WinNonlin. | single-dose administration period (Day1-Day6) | Mean residence time extrapolated from zero to infinity. MRT 0-∞ = AUMC 0-∞/AUC 0-∞. |
| Evaluate the safety of Y-3 (40 mg) in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic by Incidence of subject getting abnormal results of physical examinations after treatment. | This study comprises a screening period (Day -28 to Day -1), a baseline period (Day -1), a treatment period (Day1 - Day6), and a safety follow-up period (Day10±1). | Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. Physical examinations will be conduct by the investigator through observation. |
| Evaluate the Tmax of Y-3 (40 mg ) in subjects with mild hepatic insufficiency , moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by venous blood and Phoenix WinNonlin. | single-dose administration period (Day1-Day6) | Time to reach maximum observed plasma concentration. It was obtained directly from the measured plasma concentration-time data. |
| Evaluate the safety of Y-3 (40 mg) in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic functionby Incidence of subject getting abnormal results of respiration after treatment. | This study comprises a screening period (Day -28 to Day -1), a baseline period (Day -1), a treatment period (Day1 - Day6), and a safety follow-up period (Day10±1). | Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. respiration will be assessed by nurses. |
| Evaluate the safety of Y-3 (40 mg) in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic functionby Incidence of subject getting abnormal results of pulse after treatment. | This study comprises a screening period (Day -28 to Day -1), a baseline period (Day -1), a treatment period (Day1 - Day6), and a safety follow-up period (Day10±1). | Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. pulse will be assessed by nurses. |
| Evaluate the safety of Y-3 in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by Incidence of subject getting abnormal results of body temperature after treatment. | This study comprises a screening period (Day -28 to Day -1), a baseline period (Day -1), a treatment period (Day1 - Day6), and a safety follow-up period (Day10±1). | Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. body temperature will be assessed by thermometer. |
| Evaluate the safety of Y-3 (40 mg ) in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by Incidence of subject getting abnormal results of 12-lead ECG after treatment. | This study comprises a screening period (Day -28 to Day -1), a baseline period (Day -1), a treatment period (Day1 - Day6), and a safety follow-up period (Day10±1). | Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. 12-lead ECG will be analyzed by single RR Heart Rate, aggregate PR Interval, aggregate QRS Duration, aggregate RR Interval, aggregate QT Interval, aggregate QTC Interval. Normal range is provided by the site. |
| Evaluate the safety of Y-3 (40 mg) in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by Incidence of abnormal results of laboratory tests after treatment. | This study comprises a screening period (Day -28 to Day -1), a baseline period (Day -1), a treatment period (Day1 - Day6), and a safety follow-up period (Day10±1). | Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. Laboratory tests are composed of hematology, urinalysis, serum chemistry, coagulation test. Normal range is provided by the site. |
| Evaluate the safety of Y-3 (40 mg) in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by the rates of adverse events after treatment. | This study comprises a screening period (Day -28 to Day -1), a baseline period (Day -1), a treatment period (Day1 - Day6), and a safety follow-up period (Day10±1). | An AE is defined as any untoward medical event that occurs after receiving a drug or treatment or any deterioration of a disease or symptom that existed before receiving the investigational product or treatment (excluding the disease studied in this trial) in a subject or a clinical investigation subject, whether or not considered related to the investigational product or treatment. Therefore, an AE can be a discomfort sign (including an abnormal laboratory finding), symptom, or transient disease beyond any indication, whether or not related to the investigational product or treatment. The investigator will name each AE reported during the study by MedDRA PT and evaluate their severity using the criteria of mild, moderate and severe. The relevance evaluation is divided into 5 grades: 1-certainly related; 2- probably/likely related; 3-possibly related; 4-unlikely related; 5 not related. |
| Evaluate the safety of Y-3 in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic functionby Incidence of subject getting abnormal results of blood pressure after treatment. | This study comprises a screening period (Day -28 to Day -1), a baseline period (Day -1), a treatment period (Day1 - Day6), and a safety follow-up period (Day10±1). | Record changes from baseline to post-treatment, listing deviations from normal ranges post-treatment. blood pressure will be assessed by electronic sphygmomanometer. |
| Evaluate the t1/2 of Y-3 (40 mg ) in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by venous blood and Phoenix WinNonlin. | single-dose administration period (Day1-Day6) | Terminal elimination half-life. t1/2 = ln2/λ |
| Evaluate the λz of Y-3 (40 mg ) in subjects with mild hepatic insufficiency, moderate hepatic insufficiency and gender, age, and weight matching normal hepatic function by venous blood and Phoenix WinNonlin. | single-dose administration period (Day1-Day6) | Terminal-phase elimination rate constant, slope of curves terminal segment at semi-log concentration-time curve calculated by linear regression. |
Contacts
Primary ContactShuang Li
Outcome results
None listed