Pharmacokinetics and Safety Study of YZJ-1139 in Subjects With Severe Renal Impairment and Normal Renal Impairment

A Phase 1 Open-Label Single-Dose Study to Assess the Pharmacokinetics and Safety of YZJ-1139 in Subjects With Severe Renal Impairment and Renal Impairment

Objective：

1. To evaluate the pharmacokinetics of YZJ-1139 tablets in patients with severe renal impairment and in subjects with normal renal impairment.
2. To evaluate the safety of YZJ-1139 tablets in patients with severe renal impairment and in subjects with normal renal impairment.

Study Overview

• Status: Active, not recruiting
• Conditions: Insomnia; Renal Impairment
• Intervention / Treatment: Drug: YZJ-1139

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Bengbu, China
    • The First Affiliated Hospital of Bengbu Medical University
  • Xuzhou, China
    • The First Affiliated hospital of Xuzhou Medical University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Zhongda Hospital Southeast University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Entry criteria（Group A-Severe Renal Impairment Group）:

1. Male or female subjects aged 18-65 years (inclusive).
2. Weight ≥ 50.0 kg for males, or ≥ 45.0 kg for females, and body mass index (BMI) in the range of 19.0 ~ 28.0 kg/m2 (inclusive).
3. Subjects has been diagnosed with chronic kidney disease (more than 3 months) and have stable renal function (absolute eGFR change within 25% at least 1 month at screening), absolute eGFR at screening meets the renal function classification criteria, severe renal insufficiency: 15 ~ 29 mL/min;.
4. Subjects of childbearing potential (including partners) have no family planning or donate sperm/eggs from 2 weeks before screening to 3 months after dosing, and voluntarily take appropriate contraceptive measures;
5. Subjects who are able to understand and willing to complete the study in strict compliance with the clinical protocol and sign the informed consent form

Exclusion criteria(Group A-Severe Renal Impairment Group):

1. Allergic constitution, such as those with a known history of allergies to drugs, food or other substances, or those with a history of allergies to YZJ-1139 tablets or similar orexin receptor antagonist drugs and excipients;
2. Subjects with difficulty swallowing tablets, and special dietary requirements who cannot accept a unified diet;
3. Subjects who have poor peripheral venous access or cannot tolerate venous puncture or have a history of needle and blood fainting;
4. Subjects who have undergone surgery within 30 days prior to screening, or plan to undergo surgery during the study;
5. 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;
6. Patients who have received kidney transplantation and/or require renal dialysis during the trial.
7. Except for the disease causing renal dysfunction itself, those who have previously or currently suffered from other serious systemic organ diseases, including respiratory, digestive, endocrine, malignant tumor, blood, mental/nervous system serious diseases, which were judged by the investigator to be unsuitable for participation in this trial;
8. Subjects with ALT and/or AST > 2 ULN and/or TBIL > 1.5 ULN, Hb < 80 g/L, QTcF > 450 ms in males and QTcF > 470 ms in females by ECG.
9. Subjects with poorly controlled hypertension (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg) or heart rate > 120bmp.
10. Patients with diabetic nephropathy HbAlc (glycosylated hemoglobin) > 8.5% or fasting blood glucose > 8.5 mmol/L, or stable treatment regimen for less than 1 month before screening.
11. Subjects with active HBV infection (HBV DNA copy number ≥ 104 copies/mL must be excluded if HBsAg is positive), or those who are positive in any index screening of HCV, human immunodeficiency virus antibody, syphilis antibody.
12. Subjects with a history of drug abuse, drug use within 6 months before screening, or positive drug abuse screening;
13. Subjects who frequently consume alcohol within 3 months prior to screening, i.e., consuming 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 who cannot stop using any alcohol products during the study, or alcohol breath test result > 0.0 mg/100 mL;
14. Subjects who have donated blood or experienced massive blood loss (> 400 mL) within 3 months prior to screening, received blood transfusions or used blood products, planned to donate blood during the trial period or within 1 month after the end of the trial;
15. Subjects who have consumed excessive tea, coffee and/or caffeine-containing beverages (more than 8 cups, 1 cup ≈ 250 mL) daily during the 3 months before screening;
16. Subjects smoke an average of 5 or more cigarettes per day within 3 months prior to screening, or those who cannot stop using any tobacco products during the study;
17. Subjects who have participated in any clinical trial and have used clinical trial drugs within 3 months prior to screening, or plan to participate in other clinical trials during the study;
18. Subjects who have received vaccination within 30 days prior to screening, or plan to receive vaccination during the study;
19. Subjects who have used any CYP3A4 enzyme inducer or inhibitor within 30 days (or 5 half-lives, whichever is longer) prior to administration;
20. Subjects who have used any prescription drugs, over-the-counter drugs, vitamin products, health products or Chinese herbal medicines other than those for the treatment of renal insufficiency and or its concomitant chronic diseases within 14 days before administration;
21. Subjects who started taking new drugs, dosage forms or adjusted current doses for the treatment of chronic kidney disease and its combined chronic diseases within 14 days before administration;
22. Subjects who have consumed special diets (including grapefruit, chocolate, xanthine-rich or alcohol-rich foods/beverages) within 48 h before administration;
23. Lactating women, or women who test positive for pregnancy;
24. Subjects with acute illness from screening to prior to administration;
25. Those who, in the opinion of the investigator, are not suitable for inclusion.

Entry criteria（Group B-Healthy Subject Group）:

1. Subjects aged 18 to 65 years (inclusive), matched with renal impairment for age and sex (each subject in Group B within± 10 years of the mean for Group A and with a mean of ± 1 case for Group A by gender)；
2. Weight ≥ 50.0 kg for males, or ≥ 45.0 kg for females, and body mass index (BMI) in the range of 19.0 ~ 28.0 kg/m2 (inclusive), matched to BMI with renal impairment group (each subject in Group B within ±15% of mean in Group A by BMI).
3. Normal renal function, 90 mL/min ≤ absolute eGFR < 130 mL/min;
4. Subjects with normal physical examination, vital signs (normal range refers to central SOP), 12-lead ECG, laboratory tests, imaging and abdominal ultrasonography results during the screening period or abnormal but no clinical significance as judged by the investigator;
5. Subjects of childbearing potential (including partners) have no family planning or donate sperm/eggs from 2 weeks before screening to 3 months after dosing, and voluntarily take appropriate contraceptive measures;
6. Subjects who are able to understand and willing to complete the study in strict compliance with the clinical protocol and sign the informed consent form.

Exclusion criteria(Group B-Healthy Subject Group):

1. Allergic constitution, such as those with a known history of allergies to drugs, food or other substances, or those with a history of allergies to YZJ-1139 tablets or similar orexin receptor antagonist drugs and excipients;
2. Subjects with difficulty swallowing tablets, and special dietary requirements who cannot accept a unified diet;
3. Subjects who have poor peripheral venous access or cannot tolerate venous puncture or have a history of needle and blood fainting;
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. Subjects who have a history of other serious diseases and chronic diseases such as respiratory system, circulatory system, digestive system, urinary system, blood system, endocrine system, immune system, nervous system, mental system;
6. Those who are positive in any index screening of hepatitis B virus surface antigen, Treponema pallidum-specific antibody, human immunodeficiency virus antibody,or hepatitis C virus antibody；
7. 12) Subjects with a history of drug abuse, drug use within 6 months before screening, or positive drug abuse screening;
8. Subjects who frequently consume alcohol within 3 months prior to screening, i.e., consuming more than 14 units of alcohol per week (1 unit = 360 mL of beer or 45 mL of 40% spirits, alcohol or 150 mL of wine), or who cannot stop using any alcohol products during the study, or whose alcohol breath test result > 0.0 mg/100 mL;
9. Subjects who have donated blood or experienced massive blood loss (> 400 mL) within 3 months prior to screening, received blood transfusions or used blood products, planned to donate blood during the trial period or within 1 month after the end of the trial;
10. Subjects who have consumed excessive tea, coffee and/or caffeine-containing beverages (more than 8 cups, 1 cup ≈ 250 mL) daily during the 3 months before screening;
11. Subjects smoke an average of 5 or more cigarettes per day within 3 months prior to screening, or those who cannot stop using any tobacco products during the study;
12. Subjects who have participated in any clinical trial and have used clinical trial drugs within 3 months prior to screening, or plan to participate in other clinical trials during the study;
13. Subjects who have undergone surgery within 30 days prior to screening, or plan to undergo surgery during the study;
14. Subjects who have received vaccination within 30 days prior to screening, or plan to receive vaccination during the study;
15. Subjects who have used any CYP3A4 enzyme inducer or inhibitor within 30 days (or 5 half-lives, whichever is longer) prior to administration;
16. Subjects who have taken any prescription drugs, over-the-counter drugs, health products, vitamins, and Chinese herbal medicines within 14 days before administration;
17. Subjects who have consumed special diets (including grapefruit, chocolate, xanthine-rich or alcohol-rich foods/beverages) within 48 h before administration;
18. Lactating women, or women who test positive for pregnancy;
19. Subjects with acute illness from screening period to pre-dose;
20. Those who, in the opinion of the investigator, are not suitable for inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: Severe Renal Impairment	Drug: YZJ-1139; Single oral dose, 20 mg tablet
Experimental: Group B: Normal Renal Impairment	Drug: YZJ-1139; Single oral dose, 20 mg tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of YZJ-1139	Cmax is defined as the maximum concentration of drug	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
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		From Day 1 to Day 7
Area Under the Plasma Concentration-time Curve From Time 0 to the Last Measurable Concentration (AUC0-t) 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
Area Under the Plasma Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-∞) of YZJ-1139	AUCinf is defined as the concentration of drug extrapolated to infinite time	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
Mean Residence Time (MRT0-t) of YZJ-1139		From Day 1 to Day 3
Renal Excretion (Ae) of YZJ-1139		From Day 1 to Day 3
renal clearance (CLR) of YZJ-1139		From Day 1 to Day 3

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2024
• Primary Completion (Estimated): November 10, 2024
• Study Completion (Estimated): December 25, 2024

Study Registration Dates

• First Submitted: October 31, 2024
• First Submitted That Met QC Criteria: October 31, 2024
• First Posted (Estimated): November 4, 2024

Study Record Updates

• Last Update Posted (Estimated): November 4, 2024
• Last Update Submitted That Met QC Criteria: October 31, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency
• Other Study ID Numbers: YZJ-1139-1-12

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No