Pharmacokinetics and Safety of MDR-001 in Mild and Moderate Hepatic Impairment

Official title

A Phase I Clinical Study to Evaluate the Pharmacokinetics and Safety of MDR-001 Tablets in Patients With Mild and Moderate Hepatic Impairment and Matched Participants With Normal Hepatic Function

Overview

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

• Drug MDR-001
  Participants receive a single oral dose of MDR-001

Primary outcome measures

• Primary pharmacokinetic (PK) parameters of MDR-001 [Time frame: 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).]
• Primary pharmacokinetic (PK) parameters of MDR-001 [Time frame: 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).]
• Primary pharmacokinetic (PK) parameters of MDR-001 [Time frame: 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).]

Secondary outcome measures (4)

• Secondary pharmacokinetic parameters [Time frame: 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).]
• Secondary pharmacokinetic parameters [Time frame: 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).]
• Secondary pharmacokinetic parameters [Time frame: 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).]
• Secondary pharmacokinetic parameters [Time frame: 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).]

Eligibility criteria

Inclusion criteria

• 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.
• Participants (including their partners) must have no pregnancy plan and voluntarily take effective contraceptive measures from screening until 6 months after study drug administration.
• Age 18 to 70 years (inclusive), male or female.
• Male body weight ≥50 kg, female body weight ≥45 kg; body mass index (BMI) between 18 and 32 kg/m² (inclusive).
• Estimated glomerular filtration rate (eGFR, calculated by CKD-EPI formula) ≥60 mL/min/1.73m².
• 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

• Allergic constitution, including severe drug allergy or history of drug anaphylaxis; known allergy to the study drug or any of its components.
• 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.
• Dysphagia or any gastrointestinal disease affecting drug absorption, including frequent nausea or vomiting from any cause; active peptic ulcer; constipation.
• 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).
• 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.
• 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.
• 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.
• Use of another investigational drug within 3 months before screening, or planned participation in another clinical study during this study.
• Use of CYP3A4 inhibitors/inducers or P-gp inhibitors within 14 days before first dose, or planned use during the study.
• Pregnant or breastfeeding women, or positive pregnancy test.
• 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.
• Any other reason judged by the investigator as unsuitable for enrollment.

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 · 1 center

• The First Hospital of Jilin University — Changchun

Identifiers

NCT: NCT07550634 · MDR-001-CN-07

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗