Advanced Solid Tumor, Esophageal Cancer
Conditions
Brief summary
To evaluate the pharmacokinetics and safety of Larotinib in subjects with mild and moderate hepatic function impairment and healthy subjects in a single-center, non-randomized, open, single-dose administration
Detailed description
A phase I, a single-center, non-randomized, open, single-dose administration study to explore the safety, pharmacokinetics of Larotinib in subjects with mild and moderate hepatic function impairment and healthy subjects with normal hepatic function. This study is divided into four cohorts, cohort A and cohort C in healthy subjects, cohort B for mild hepatic function impairment participants, cohort D for moderate hepatic function impairment, participants in cohort A and cohort B, group C and group D should be matched in terms of sex, age, and body mass index (BMI). A total of 32 subjects, 8 in each cohort, both male and female, are planned to be enrolled. If a complete PK blood sample is not collected due to subjects' early withdrawal from the study, new subjects will be enrolled to meet the pharmacokinetic parameters that can be evaluated for each cohort of 8 subjects.
Interventions
DRUGLarotinib
Capsules, Oral, 350 mg, single dose, one day
Sponsors
Sunshine Lake Pharma Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study is divided into four cohorts: healthy subjects in cohort A and C, mild liver function impairment subjects in cohort B, and moderateliver function impairment subjects in cohort D. Cohorts A and B, C and D should be matched in terms of gender, age, and body mass index (BMI).
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* healthy subjects with normal hepatic function (cohorts A and C) : * 1\. Sign the informed consent form before the trial； * 2\. subjects and must be 18 to 70 years of age inclusive, Male or female. body weight \>50 kg (male) or ≥45 kg (female) at screening. (BMI) : 18-30 kg/m\^2, (including critical value) \[BMI= weight (kg)/height\^2 (m\^2)\] (BMI matching ±15% with liver dysfunction cohort); * 3.Must be in good health as determined by past medical history, physical examination, vital signs, ECG, and laboratory tests at Screening； * 4.Subjects (including partners) have no pregnancy plan within 6 months after the last dose of study drug and voluntarily take effective contraceptive measures. * Subjects with mild/ Moderate hepatic Impairment (cohorts B and D) : * 1\. Sign the informed consent form before the trial. * 2\. subjects and must be 18 to 70 years of age inclusive, Male or female. body weight \>50 kg (male) or ≥45 kg (female) at screening. (BMI) : 18-30 kg/m\^2； * 3\. Must satisfy the criteria for hepatic Impairment as evidenced by a Child-Pugh class of A or B at Screening:Class A; Mild; Child-Pugh score 5-6；Class B; Moderate; Child-Pugh score 7-9 * 4\. The liver function status of the subjects was determined to be stable between 1 month before taking the experimental drug and the end of the study, with no significant change. * 5\. Subjects (including partners) have no pregnancy plan within 6 months after the last dose of study drug and voluntarily take effective contraceptive measures.
Exclusion criteria
* ALL subjects * 1\. The subject has been diagnosed with acquired immune deficiency syndrome (AIDS), or tests positive for human immunodeficiency virus (HIV). * 2\. Currently suffering from any bleeding disease, such as gastric and duodenal ulcer * 3\. Those who had undergone major surgery within 6 months before the screening period or the surgical incision did not completely heal; * 4\. History of hand foot syndrome; * 5\. Those who have a history of liver cancer or other malignant tumors before signing the informed consent * 6\. Those who have a history of gastrointestinal and renal diseases or surgery that may affect drug absorption, distribution, metabolism and excretion within 6 months before screening, or have diseases that can reduce compliance * 7\. Take any food or beverage products containing alcohol, caffeine, xanthine and grapefruit within 48 hours prior to the first dose. * 8\. The subject has received blood within 1 month, or donated loss of blood over 400 mL within 3 months prior to the screening * 9\. Have a history of alcoholism or positive alcohol breath test during the screening period; * 10\. Those who smoke more than 5 cigarettes a day or habitually use nicotine containing products 3 months before screening * 11\. Those who had a history of drug abuse or used drugs within 2 years before screening or those who were positive for urinary drug screening during the screening period Allergic constitution * 12\. Allergic constitution * 13\. Within 28 days before screening, inhibitors or inducers of CYP3A4, cyp2c8, CYP2C19 and P-gp were used * 14\. Participated in any other intervention clinical trial within 3 months before screening * 15\. Female subjects with positive pregnancy test results or breastfeeding during screening; * 16\. Any other circumstances that the investigator considers unsuitable for participation in this study * The following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | Day 1 to Day 7 | Maximum plasma concentration of study drugs |
| Area Under Curve From 0 to Infinity (AUC0-infinity) | Day 1 to Day 7 | AUC0-infinity represents the area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event | Day-7 to Day 14 | New abnormal findings or worsening of baseline conditions were reported as Adverse Events. |
Countries
China
Contacts
CONTACTJia Miao, MD
CONTACTHong Tang, MD
PRINCIPAL_INVESTIGATORJia Miao, MD
West China Hospital
Outcome results
None listed