Pharmacokinetics and Safety Study of YZJ-1139 in Subjects With Mild, Moderate and Normal Hepatic Impairment

NCT06671509 | Completed Phase 1

• 1 other identifier: YZJ-1139-1-11
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Conditions

Insomnia; Hepatic Impairment

Outcome Measures

Primary Outcomes (7)

• Maximum Observed Plasma Concentration (Cmax) of YZJ-1139

  Cmax is defined as the maximum concentration of drug

  From Day 1 to Day 3

• Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUCinf) of YZJ-1139

  AUCinf is defined as the concentration of drug extrapolated to infinite time

  From Day 1 to Day 3

• Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUClast) of YZJ-1139

  AUClast is defined as the concentration of drug from time zero to the last observable concentration

  From Day 1 to Day 3

• Time of Maximum Observed Plasma Concentration (Tmax) of Entrectinib

  Tmax is defined as the time (observed time point) of Cmax.

  From Day 1 to Day 3

• Apparent Terminal Elimination Half-life (t1/2) of Entrectinib

  From Day 1 to Day 3

• Apparent Oral Clearance (CL/F) of Entrectinib

  CL/F is defined as the apparent oral clearance following administration of the drug

  From Day 1 to Day 3

• The Apparent Volume of Distribution (Vz/F) of Entrectinib

  Vz/F is defined as the apparent volume of distribution of the drug

  From Day 1 to Day 3

Secondary Outcomes (1)

• Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  From Day 1 to Day 7

Study Arms (3)

Group A: Mild Hepatic Impairment

EXPERIMENTAL

Drug: YZJ-1139

Group B: Moderate Hepatic Impairment

EXPERIMENTAL

Drug: YZJ-1139

Group C: Normal Hepatic Impairment

EXPERIMENTAL

Drug: YZJ-1139

Interventions

YZJ-1139 DRUG

Single oral dose, 20 mg tablet

Group A: Mild Hepatic Impairment; Group B: Moderate Hepatic Impairment; Group C: Normal Hepatic Impairment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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);
• 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;
• 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);
• 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:
• 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).
• 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:
• The demographic mean of subjects in the normal liver function group (Group C) during screening must meet the following matching criteria:
• Match the weight with the liver function impairment group (Group A+Group B), with a mean of ± 10 kg;
• Age matched with the liver function impairment group (Group A+Group B), with a mean of ± 10 years;
• Match with the liver function impairment group (Group A+Group B) by gender, with a mean of ± 1 case;

You may not qualify if:

• 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;
• 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);
• Screening for individuals who have had severe infections, trauma, gastrointestinal surgery, or other surgical procedures within the first 4 weeks;
• 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;
• 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;
• 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);
• 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;
• 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;
• Individuals with a history of drug use, drug abuse, or positive drug abuse screening;
• Pregnant or lactating women, or women who test positive for pregnancy;
• Patients with difficulty swallowing tablets and special dietary requirements who cannot accept a unified diet;
• Individuals who cannot tolerate venous puncture or have a history of needle and blood fainting;
• The subject has any of the following conditions: drug-induced liver injury; History of liver transplantation; Cirrhotic patients with liver failure, hepatic encephalopathy, hepatocellular carcinoma (excluding those with Barcelona stage 0 or curative treatment), hepatorenal syndrome, esophageal and gastric variceal bleeding and other complications deemed inappropriate by researchers;
• Patients with primary biliary cirrhosis and biliary obstruction;
• The laboratory test results during screening meet any of the following criteria: (a) alanine aminotransferase (ALT) or aspartate aminotransferase (AST)\>10 × ULN; (b) Absolute value of neutrophils (NE #)\<0.75 × 109/L; (c) Hemoglobin (HGB)\<60 g/L; (d) Alpha fetoprotein (AFP)\>100 ng/mL;

Sponsors & Collaborators

• Shanghai Haiyan Pharmaceutical Technology Co., Ltd.: lead

Study Sites (1)

The First Hospital of Jilin University

Changchun, Jilin, China

Location

MeSH Terms

Conditions

Sleep Initiation and Maintenance Disorders

Condition Hierarchy (Ancestors)

Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Mental Disorders

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Non-randomized
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single dose

Study Record Dates

• First Submitted: November 1, 2024
• First Posted: November 4, 2024
• Study Start: March 22, 2024
• Primary Completion: April 18, 2024
• Study Completion: August 7, 2024
• Last Updated: November 4, 2024

Record last verified: 2024-10

Locations

CN (1)