Liver Dysfunction
Conditions
Brief summary
To evaluate the pharmacokinetic difference of anlotinib hydrochloride capsule between mild/moderate liver dysfunction subjects and healthy subjects, and to provide basis for formulating the clinical drug regimen for patients with liver dysfunction.
Interventions
Anlotinib hydrochloride is a muti-target tyrosine kinase inhibitor
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Criteria 1 to 4 are applicable to all subjects. 1. The subjects volunteered to participate in the study, signed the informed consent, and had good compliance; 2. Age: 18-75 years old (including both end values) (the healthy subject group and the liver dysfunction group are age matched, the mean is ± 10 years); Both male and female (healthy subjects group and liver dysfunction group were matched by gender, mean ± 1 case); 3. Body mass index (BMI) ≥ 18 and ≤ 30 kg / m2, and male weight ≥ 50 kg or female weight ≥ 45 kg (weight matching between healthy subjects and liver dysfunction group, mean ± 10%); 4. Female subjects of childbearing age should agree to use contraceptive measures (such as IUDs, contraceptives or condoms) during the study and within 6 months after the end of the study; Serum pregnancy test was negative within 7 days before study enrollment, and must be a non lactating subject; Male subjects should agree to use contraceptives during the study period and within 6 months after the end of the study period; * Criteria 5 to 8 are applicable to subjects with liver dysfunction. 5. For the subjects with liver dysfunction, they are diagnosed as chronic (≥ 6 months) stable liver function impairment through past medical history, physical examination, serological indicators (such as albumin, bilirubin, glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, prothrombin time, etc.), liver biopsy or imaging (such as computed tomography, magnetic resonance imaging, ultrasound, laparoscopy, etc.); 6. Subjects with liver dysfunction caused by previous primary liver diseases and assessed as grade A / mild (5-6 points) or grade B / moderate (7-9 points) according to child Pugh grading score (albumin was not used within 14 days); 7. The main organs have good functions and meet the following standards: The blood routine examination shall meet the following standards (no blood transfusion or correction with hematopoietic stimulator drugs within 7 days before screening): hemoglobin (Hgb) ≥ 90g / L; Neutrophil absolute value (neut) ≥ 1.5 × 109/L; Biochemical examination shall meet the following standards: serum creatinine (CR) ≤ 1.5 × ULN or creatinine clearance rate (CCR) ≥ 60ml / min; Liver function test shall meet the following standards: alanine transferase (ALT) and aspartate transferase (AST) ≤ 5 × ULN; Coagulation function test shall meet the following standards: prothrombin time (PT) extension ≤ 6S, prothrombin activity (PTA) ≥ 40%; Cardiac color Doppler evaluation: left ventricular ejection fraction (LVEF) ≥ 50%; 8. No drugs affecting CYP3A4 were used within 2 weeks before the study; * Criteria 9, 10 are applicable to healthy subjects. 9. Main organ function is good, laboratory examination (blood routine, blood biochemistry, coagulation function, etc.), cardiac color ultrasound, 12 lead electrocardiogram, abdominal B-ultrasound and other examinations are normal or abnormal, but they are judged by the investigator to be of no clinical significance; 10. Those who did not use any prescription drugs, over-the-counter drugs, Chinese herbal medicines or food supplements within 2 weeks before the study medication;
Exclusion criteria
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak concentration (Cmax) | predose, 1,2,4,8,11,24,48,96,144,192,240,336 hours after administration | Maximum plasma drug concentration |
| Area under curve (0-t) | predose, 1,2,4,8,11,24,48,96,144,192,240,336 hours after administration | Area under the plasma concentration-time curve from time 0 to last time of quantifiable concentration |
| Area under curve (0-∞) | predose, 1,2,4,8,11,24,48,96,144,192,240,336 hours after administration | Area under the plasma concentration-time curve from time 0 and extrapolated to infinite time |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent distribution volume (Vd/F) | predose, 1,2,4,8,11,24,48,96,144,192,240,336,hours after administration | Apparent distribution volume (Vd/F) |
| Time to reach maximum concentration (TMAX) | predose, 1,2,4,8,11,24,48,96,144,192,240,336,hours after administration | Time to reach maximum concentration (TMAX) |
| Adverse event rate | From the first administration to 15 days after the administration | Incidence and severity of adverse events and serious adverse events, and abnormal laboratory examination indicators |
| Elimination half life (t1/2) | predose, 1,2,4,8,11,24,48,96,144,192,240,336,hours after administration | Elimination half life (t1/2) |
| Apparent clearance (CL/F) | predose, 1,2,4,8,11,24,48,96,144,192,240,336,hours after administration | Apparent clearance (CL/F) |
Countries
China
Contacts
Primary ContactHong Ren, Master of Medicine
Backup ContactNong Yang, Master of Medicine
Outcome results
None listed