To Evaluate the Pharmacokinetics and Safety of TQ05105 Tablet in Hepatic Impairment Subjects

Official title

Phase I Clinical Study to Evaluate the Pharmacokinetics and Safety of TQ05105 in Participants With Mild Hepatic Impairment (Child-Pugh A), Moderate Hepatic Impairment (Child-Pugh B), and Healthy Subjects

Overview

This is an open, open-label, parallel, single-dose, phase I clinical study designed to evaluate the pharmacokinetic (PK) profile of TQ05105 tablet in patients with hepatic impairment after a single dose, and to evaluate the safety of the drug in these patients after a single dose.

Interventions

• Drug TQ05105
  Janus Kinase Inhibitors/Rho-associated Kinase (JAK/ROCK) inhibitors

Primary outcome measures

• Peak concentration (Cmax) [Time frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration]
• Area under the concentration-time curve (AUC) [Time frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration]

Secondary outcome measures (8)

• Time-to-maximum concentration( Tmax) of TQ05105 and TQ12550 [Time frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration]
• Plasma half life (t1/2) [Time frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24, 48hours after administration]
• Apparent volume of distribution (Vz/F) [Time frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24, 48hours after administration]
• Terminal elimination rate (λz) [Time frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24 hours after administration]
• Curve extrapolated to infinity (AUC_%Extrap) [Time frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24 hours after administration]
• Apparent Clearance (CL/F) [Time frame: Before administration, 10, 20, 30, 45 minuets，1, 2, 3, 4, 6, 8, 12, 24 hours after administration]
• Fraction unbound(fu%) [Time frame: 0.5, 2, 6 hours after administration]
• Adverse event rate [Time frame: Baseline up to day7]

Eligibility criteria

Inclusion criteria

• Voluntarily participate in the clinical trial and sign the informed consent form, with full understanding of the trial content, procedures, and potential adverse reactions.
• Patients (including partners) have no pregnancy plans or sperm/egg donation plans from screening until 6 months after the last dose of the investigational drug, and agree to use effective contraception.
• Aged 18-75 years (inclusive), regardless of gender.
• Male participants weigh ≥50.0 kg; female participants weigh ≥45.0 kg. Body mass index (BMI) = weight (kg)/height² (m²), with BMI ranging 18.0-32.0 kg/m² (inclusive).
• Patients can communicate effectively with investigators and comply with the trial protocol.

Additional Criteria for Participants with Normal Liver Function:

• Negative serum HBsAg and Hepatitis C Virus (HCV) antibody test results.
• Weight within ±10 kg of the average weight of groups A/B; age within ±10 years of the average age of groups A/B; gender distribution similar to groups A/B (±1 participant per gender).

Additional Criteria for Participants with Impaired Liver Function:

• Chronic liver injury caused by primary liver diseases (e.g., hepatitis B/C, non-alcoholic fatty liver disease, alcoholic liver disease) or clinically diagnosed cirrhosis, classified as Child-Pugh Grade A or B.
• Stable condition within 2 weeks prior to dosing as judged by the investigator.
• No medication within 4 weeks before screening, or stable treatment regimen for underlying diseases (including liver-protective therapy).

Exclusion criteria

• History or current diagnosis of severe/chronic diseases (e.g., digestive, respiratory, neurological, cardiovascular, hematological, endocrine, oncological, immunological, or psychiatric disorders) deemed unsuitable by the investigator (except primary liver diseases and complications in participants with impaired liver function).
• Conditions affecting drug absorption, distribution, metabolism, or excretion (e.g., dysphagia) or prior gastrointestinal resection impacting these processes.
• Use of strong/moderate CYP3A4, CYP2C9, or CYP2C19 inducers/inhibitors within 4 weeks before screening.
• Known hypersensitivity to TQ05105 tablet components or allergic constitution (e.g., allergy to ≥2 substances, drug allergy history, or prone to rash/eczema/asthma).
• Average daily smoking >5 cigarettes within 3 months before screening.
• Drug abuse history or positive urine drug screen within 3 months.
• For alcoholic liver disease participants: history of excessive drinking (>2 alcohol units/day) within 1 year; for others: such history within 3 months.
• Blood donation/loss ≥200 mL or plasmapheresis within 4 weeks before screening.
• Consumption of alcohol (or positive breath test), grapefruit juice, coffee, tea, cola, or chocolate within 48 hours before dosing.
• Creatinine clearance (CLcr) <60 mL/min.
• Pregnant/lactating women, positive pregnancy test, or unprotected sex within 2 weeks before screening.
• Positive HIV antibody or Treponema pallidum-specific antibody.
• Other factors deemed unsuitable by the investigator.

Additional Exclusions for Normal Liver Function Participants:

• Use of prescription/non-prescription drugs, herbal medicines, or supplements (e.g., vitamins) within 2 weeks before screening.
• The results of physical examination during the screening period, vital signs, clinical laboratory tests (blood cell analysis (five categories), blood biochemistry, coagulation function, urine routine examination with sediment), electrocardiogram, frontal and lateral chest X-rays, abdominal ultrasound (liver, gallbladder, pancreas, spleen), and urinary system ultrasound, etc., which showed abnormal results and were determined by the research doctor to have clinical significance.
• Patients in other drug trials within 3 months or 5 half-lives (whichever longer) before screening.

Additional Exclusions for Impaired Liver Function Participants:

• Had a history of liver transplantation;
• Patients with hepatic coma within 30 days before screening;
• Patients who had used drugs that might cause acute hepatotoxicity (such as halothane and methotrexate) within 3 months before screening;
• Patients with acute liver disease caused by drug or viral infection within 2 months before screening;
• With biliary cirrhosis, liver/bile duct obstruction, cholestatic liver disease and other diseases affecting biliary excretion;
• Patients with liver failure or liver cancer, or patients with a history of esophagogastric variceal bleeding, hepatic encephalopathy, severe portal hypertension, or a portasystemic shunt within 1 year before screening who were judged by the investigator to be ineligible for the trial;
• Patients with abnormal physical examination, vital signs, clinical laboratory tests (blood cell analysis (five classification), blood biochemistry, coagulation function, urine routine and sediment), AFP, electrocardiogram, chest X-ray, echocardiography, abdominal ultrasound (liver, gallbladder, pancreas and spleen), urinary ultrasound, and routine electroencephalogram (EEG) during the screening period and judged by the research doctors as not suitable for the study;
• Patients with massive ascites on ultrasound during the screening period who were assessed by the investigators as not suitable for the trial;
• Who participated in and used any investigational drug within 1 month before screening.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• The First Affiliated Hospital of Henan University of Science & Technology — Luoyang
• The First Affiliated Hospital of Shandong First Medical University (Qianfoshan Hospital) — Jinan

Identifiers

NCT: NCT07480824 · TQ05105-I-08

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗