Hepatic Impairment (Mild and Moderate, Child-Pugh Class A and B), Hepatic Insufficiency (MeSH ID: D048550)
Conditions
Keywords
MDR-001, Hepatic impairment (mild, moderate), Child-Pugh A / Child-Pugh B, GLP-1 receptor agonist (GLP-1RA), Pharmacokinetics (PK), safety, Phase I clinical study, Matched healthy controls, Open-label
Brief summary
This is a Phase I, single-center, open-label, parallel-group study. A single oral dose of MDR-001, a GLP-1 receptor agonist, will be administered to participants with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment and to matched healthy controls. The study aims to evaluate the pharmacokinetics and safety of MDR-001 in these populations. Primary pharmacokinetic endpoints include AUC and Cmax; safety endpoints include adverse events, vital signs, ECG, and laboratory assessments.
Interventions
DRUGMDR-001
Participants receive a single oral dose of MDR-001
Sponsors
MindRank AI Ltd
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
1. Voluntary signed informed consent before any study-related activities, and ability to understand the study procedures and methods, and willingness to strictly comply with the protocol to complete the study. 2. Participants (including their partners) must have no pregnancy plan and voluntarily take effective contraceptive measures from screening until 6 months after study drug administration. 3. Age 18 to 70 years (inclusive), male or female. 4. Male body weight ≥50 kg, female body weight ≥45 kg; body mass index (BMI) between 18 and 32 kg/m² (inclusive). 5. Estimated glomerular filtration rate (eGFR, calculated by CKD-EPI formula) ≥60 mL/min/1.73m². 6. Additional criteria for participants with hepatic impairment: * Chronic liver injury caused by primary liver disease (e.g., hepatitis B, hepatitis C, autoimmune hepatitis, alcoholic liver disease, etc.). * Child-Pugh grade A or B (see Appendix 1); recent liver function and complications stable, no significant deterioration (e.g., abdominal pain, increased ascites, nausea, vomiting, anorexia, fever, or worsening of liver-related laboratory results). * Stable medication regimen (including type, dose, or frequency) for the treatment of hepatic impairment, complications, or other concomitant diseases for at least 14 days before study drug administration, with no need for adjustment (diuretics and insulin, etc., excepted); or not taking any such medications.
Exclusion criteria
1. Allergic constitution, including severe drug allergy or history of drug anaphylaxis; known allergy to the study drug or any of its components. 2. Screening ECG showing QTcF \>450 msec (males) or \>470 msec (females) (Fridericia correction); personal or family history of long QT syndrome; family history (parents, children, siblings) of sudden death before age 40; and/or personal history of unexplained syncope within 1 year before screening. 3. Dysphagia or any gastrointestinal disease affecting drug absorption, including frequent nausea or vomiting from any cause; active peptic ulcer; constipation. 4. Within 6 months before screening: severe gastrointestinal disease (e.g., active ulcer) or gastrointestinal surgery (except appendectomy, cholecystectomy, or other endoscopic procedures judged not to significantly affect gastrointestinal motility); clinically significant gastric emptying abnormality (e.g., pyloric obstruction, gastroparesis). 5. Any symptomatic bacterial, viral, parasitic, or fungal infection requiring treatment at screening (except hepatitis B or C); history of serious active infection within 1 month before screening. 6. Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2), or genetic disorders predisposing to medullary thyroid carcinoma. 7. Blood donation or blood loss ≥400 mL within 3 months before screening, or planned blood donation during the study or within 1 month after study completion. 8. Use of another investigational drug within 3 months before screening, or planned participation in another clinical study during this study. 9. Use of CYP3A4 inhibitors/inducers or P-gp inhibitors within 14 days before first dose, or planned use during the study. 10. Pregnant or breastfeeding women, or positive pregnancy test. 11. History of depression or other serious mental disorders (e.g., schizophrenia, bipolar disorder, or other severe mood or anxiety disorders); history of suicidal ideation or suicidal behavior. 12. Any other reason judged by the investigator as unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary pharmacokinetic (PK) parameters of MDR-001 | Baseline (Day 1 pre-dose) and at 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post-dose on Day 1 (single dose). | Maximum observed plasma concentration (Cmax) of MDR-001 following a single oral dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary pharmacokinetic parameters | Baseline (Day 1 pre-dose) and at 0.25, 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, and 48 hours post-dose on Day 1 (single dose). | Time to peak concentration (Tmax) |
Countries
China
Contacts
CONTACTGuodong Li, PhD
CONTACTWeixia Li, MD
PRINCIPAL_INVESTIGATORHong Zhang, MD
The First Hospital of Jilin University
Outcome results
None listed