Hepatic Impairment, Insomnia
Conditions
Brief summary
Primary Objectives: To evaluate the effect of the subjects with mild (Child Pugh A), moderate (Child Pugh B) and normal hepatic impairment on the pharmacokinetics of YZJ-1139 Secondary Objectives: To evaluate the safety of a single oral dose of YZJ-1139 in subjects with mild, moderate and normal hepatic impairment
Interventions
DRUGYZJ-1139
Single oral dose, 20 mg tablet
Sponsors
Shanghai Haiyan Pharmaceutical Technology Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Non-randomized
Intervention model description
Single dose
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. Voluntarily sign an informed consent form before the start of activities related to this trial, and be able to understand the procedures and methods of this trial, willing to strictly follow the clinical trial protocol to complete this trial; 2. The subjects (including partners) are willing to self screen and have no family planning within 3 months after the administration of the investigational drug, and voluntarily take contraceptive measures (see Appendix 1 for specific contraceptive measures); 3. On the day of signing the informed consent form, the age range is 18 to 70 years old (including both ends), both men and women are eligible; 4. The weight of male subjects shall not be less than 50 kg, and the weight of female subjects shall not be less than 45 kg; Body mass index (BMI) 18-32 kg/m2 (including both ends); 5. Creatinine clearance rate (calculated using Cockcroft Gault formula, see Appendix 2) ≥ 60 mL/min; Subjects with liver dysfunction also need to meet all the following conditions: 6. Chronic liver injury caused by primary liver diseases (such as hepatitis B, hepatitis C, autoimmune hepatitis, alcoholic liver disease, etc.) or clinically diagnosed as cirrhosis (see Appendix 3 for diagnostic criteria for cirrhosis), and liver dysfunction patients with Child Pugh grading of A or B (see Appendix 4 for Child Pugh grading). 7. Individuals who have a stable medication regimen for the treatment of liver dysfunction, complications, and other accompanying diseases for at least 14 days prior to taking the investigational drug, and whose medication does not need to be adjusted (including medication type, dosage, or frequency); Or those who have not taken medication; Subjects with normal liver function also need to meet all the following conditions: 8. The demographic mean of subjects in the normal liver function group (Group C) during screening must meet the following matching criteria: 1. Match the weight with the liver function impairment group (Group A+Group B), with a mean of ± 10 kg; 2. Age matched with the liver function impairment group (Group A+Group B), with a mean of ± 10 years; 3. Match with the liver function impairment group (Group A+Group B) by gender, with a mean of ± 1 case;
Exclusion criteria
1. Allergic constitution, such as those with a known history of allergies to two or more substances, or those with allergic diseases, or those with a history of allergies to experimental drugs or similar drugs or excipients; 2. Screening period electrocardiogram showed QTc interval (QTcF)\>470 msec in males and\>480 msec in females (corrected according to Fridericia's standard: QTcF=QT/(RR \^ 0.33), RR=60/heart rate); 3. Screening for individuals who have had severe infections, trauma, gastrointestinal surgery, or other surgical procedures within the first 4 weeks; 4. Individuals with a history of paroxysmal sleep disorder, obstructive sleep apnea, complex sleep behavior (such as dream walking, driving in dreams, etc.), severe unconscious hypoglycemia, stroke, epilepsy, and other psychiatric disorders (including anxiety, depression, etc.), convulsive diseases, and sudden onset of illness; 5. Individuals who have donated blood or lost ≥ 200 mL of blood within the first 3 months of screening, received blood transfusions or used blood products, or planned to donate blood during the trial period or within 1 month after the end of the trial; 6. Individuals who have used CYP3A4 enzyme inducers or inhibitors within one month prior to administration (or five half-lives, whichever is longer) (see Appendix 5); 7. Individuals who have consumed 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, 200mL per cup) within 2 weeks prior to administration; 8. 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% spirits, or 150 mL of wine) or those who have tested positive for alcohol screening; Screening for individuals who smoke an average of 10 or more cigarettes per day within the first 3 months; 9. Individuals with a history of drug use, drug abuse, or positive drug abuse screening; 10. Pregnant or lactating women, or women who test positive for pregnancy; 11. Patients with difficulty swallowing tablets and special dietary requirements who cannot accept a unified diet; 12. Individuals who cannot tolerate venous puncture or have a history of needle and blood fainting; 13. For other reasons, researchers believe that it is not suitable for inclusion; If a subject with liver function impairment meets any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Apparent Volume of Distribution (Vz/F) of Entrectinib | From Day 1 to Day 3 | Vz/F is defined as the apparent volume of distribution of the drug |
| Maximum Observed Plasma Concentration (Cmax) of YZJ-1139 | From Day 1 to Day 3 | Cmax is defined as the maximum concentration of drug |
| Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of YZJ-1139 | From Day 1 to Day 3 | AUCinf is defined as the concentration of drug extrapolated to infinite time |
| Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUClast) of YZJ-1139 | From Day 1 to Day 3 | AUClast is defined as the concentration of drug from time zero to the last observable concentration |
| Time of Maximum Observed Plasma Concentration (Tmax) of Entrectinib | From Day 1 to Day 3 | Tmax is defined as the time (observed time point) of Cmax. |
| Apparent Terminal Elimination Half-life (t1/2) of Entrectinib | From Day 1 to Day 3 | — |
| Apparent Oral Clearance (CL/F) of Entrectinib | From Day 1 to Day 3 | CL/F is defined as the apparent oral clearance following administration of the drug |
Secondary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | From Day 1 to Day 7 |
Countries
China
Outcome results
None listed