Normal Liver Function Subject, Subjects With Liver Function Injury
Conditions
Brief summary
Evaluate the pharmacokinetic differences of the main metabolite 116-N1 of JT001 in subjects with mild and moderate liver function impairment and those with normal liver function, providing a basis for formulating clinical medication plans for patients with liver function impairment;
Detailed description
This study adopts a non randomized, open, parallel controlled, single dose experimental design and is divided into three experimental groups: mild liver function impairment group (Group A), moderate liver function impairment group (Group B), and normal liver function subject group (Group C). Subjects in each experimental group took 0.3g of JT001 orally on an empty stomach and collected blood samples before and after administration for pharmacokinetic analysis. After both groups A and B were enrolled, Group C subjects will be enrolled subsequently and should be matched with subjects with liver function impairment (Group A and Group B) as following: The average body weight of Group C is within ± 10 kg of the average body weight of the group of subjects with liver function impairment (Groups A and B). The average age of Group C is within ± 10 years of the average age of the group of subjects with liver function impairment (Groups A and B). The number of subjects of each gender in Group C is similar to that in the liver function impairment group (A and B groups) (± 1 subject/gender). The study is divided into three stages: screening period, baseline period, and experimental period.
Interventions
JT001 single dose, 0.3g
Sponsors
Sponsor GmbH
Shanghai Vinnerna Biosciences Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Parallel
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. On the day of signing the informed consent form, the age range is 18 to 70 years (including both ends), both male and female are eligible; 2. Male subjects weighing no less than 50 kg and female subjects weighing no less than 45 kg; Body mass index (BMI) 18-32 kg/m2 (including both ends), where BMI=weight (kg)/height 2 (m2); Subjects with normal liver function also need to meet all the following conditions: 3. When screening, the following demographic matching criteria must be met: 1. Match the weight with the liver function impairment group, with a mean of ± 10 kg; 2. Age matched with the liver function impairment group, with a mean of ± 10 years; 3. Gender matching was performed with the liver function impairment group, with a mean of ± 1 case; Subjects with liver function impairment also need to meet all the following conditions: 4. Patients with chronic liver injury caused by primary liver diseases (such as hepatitis B, hepatitis C, autoimmune hepatitis, alcoholic liver disease, etc.) and stable liver function (without any liver disease related medical records within 14 days before taking the study drug, except for regular follow-up and medication) with liver dysfunction classified as A or B by Child-Pugh ; 5. Clinically diagnosed as liver cirrhosis; 6. Those who have a stable medication plan for the treatment of liver function damage, complications, and other accompanying diseases for at least 14 days before taking the study drug, and the medication does not need to be adjusted (including medication type, dosage, or frequency); Or those who have not taken medication; 7. Estimated Glomerular filtration rate (eGFR, calculated using the CKD-EPI formula) ≥ 60 mL/min/1.73m2;
Exclusion criteria
1. The electrocardiogram shows a QTc interval (QTcF) of\>450 msec for males and\>470 msec for females (corrected according to Fridericia's standard); 2. Screening for individuals with severe infections, trauma, gastrointestinal surgery, or other major surgical procedures within the first 4 weeks; 3. Those who have received the vaccine within 14 days before screening or plan to receive the vaccine during the study period; 4. Those who donate blood or have a blood loss of ≥ 400 mL within the first 3 months of screening, or intend to donate blood during or within 1 month after the trial; 5. Screening for potent inhibitors or inducers of Pg-P or BCRP that have been used within the previous month (see Attachment 4); 6. Those who have taken a special diet (including dragon fruit, mango, grapefruit, and/or xanthine diet, chocolate) and/or consumed excessive amounts of tea, coffee, grapefruit/grapefruit juice, and/or caffeinated beverages (an average of 8 or more cups per day, 200 mL per cup) within 2 weeks before administration; 7. Screening for alcoholics within the first three months, i.e. those who consume more than 14 units of alcohol per week (1 unit=360 mL of beer, or 45 mL of 40% alcohol or 150 mL of wine) or those who are positive for alcohol screening; 8. Individuals who smoke an average of 10 or more cigarettes per day within the first 3 months of screening; Subjects with normal liver function who meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tmax of the main metabolite 116-N1 of JT001; | From time zero up to 72 hours post-dose following oral administration of JT001 | Time to maximum observed concentration of the main metabolite 116-N1 of JT001; |
| The Cmax of the main metabolite 116-N1 of JT001; | From time zero up to 72 hours post-dose following oral administration of JT001 | maximum observed plasma concentration |
| The AUC0-t of the main metabolite 116-N1 of JT001; | From time zero up to 72 hours post-dose following oral administration of JT001 | area under the curve from time zero to the last measurable concentration |
| The AUC0-inf of the main metabolite 116-N1 of JT001; | From time zero up to 72 hours post-dose following oral administration of JT001 | area under curve from time zero to infinity |
| t1/2 of the main metabolite 116-N1 of JT001; | From time zero up to 72 hours post-dose following oral administration of JT001 | Terminal phase half-life of the main metabolite 116-N1 of JT001; |
| CL/F of the main metabolite 116-N1 of JT001; | From time zero up to 72 hours post-dose following oral administration of JT001 | The clearance of the main metabolite 116-N1 of JT001; |
| Vz/F of the main metabolite 116-N1 of JT001; | From time zero up to 72 hours post-dose following oral administration of JT001 | The apparent volume of distribution of the main metabolite 116-N1 of JT001; |
| The severity of SAE | From Day 1(first dose) to Day7 | The severity of SAE |
| The Number of participants with SAE | From Day 1(first dose) to Day7 | The Number of participants with SAE |
| The severity ofclinical symptoms abnormalities(e.g.,Dizziness, headache, nausea, abdominal pain, fatigue, drowsiness） | From Day 1(first dose) to Day7 | The severity ofclinical symptoms abnormalities(e.g.,Dizziness, headache, nausea, abdominal pain, fatigue, drowsiness） |
| The Number of participantswith abnormal clinical symptoms(e.g.,Dizziness, headache, nausea, abdominal pain, fatigue, drowsiness） | From Day 1(first dose) to Day7 | The Number of participantswith abnormal clinical symptoms(e.g.,Dizziness, headache, nausea, abdominal pain, fatigue, drowsiness） |
| The severity of vital signs abnormalities | From Day 1(first dose) to Day7 | The severity of Pulse abnormalities |
| The Number of participantswith abnormal vital signs | From Day 1(first dose) to Day7 | The Number of participantswith abnormal Pulse |
| The severity of abnormal physical examinations findings | From Day 1(first dose) to Day7 | The severity of abnormal physical examinations findings |
| The Number of participantswith abnormal physical examinations findings | From Day 1(first dose) to Day7 | The Number of participantswith abnormal physical examinations findings |
| The severity of abnormal laboratory tests results | From Day 1(first dose) to Day7 | The severity of abnormal laboratory tests results |
| The Number of participantswith abnormal laboratory tests results | From Day 1(first dose) to Day7 | The Number of participantswith abnormal laboratory tests results |
| The severity of electrocardiogram (ECG) abnormalities | From Day 1(first dose) to Day7 | The severity of Heart rate abnormalities |
| The Number of participants with electrocardiogram (ECG) abnormalities | From Day 1(first dose) to Day7 | The Number of participants with Heart rate abnormalities |
Countries
China
Outcome results
None listed