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

Официальное название

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

Обзор

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.

Вмешательства

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

Первичные конечные точки

• Primary pharmacokinetic (PK) parameters of MDR-001 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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).]

Вторичные конечные точки (4)

• Secondary pharmacokinetic parameters [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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).]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The First Hospital of Jilin University — Changchun

Идентификаторы

NCT: NCT07550634 · MDR-001-CN-07

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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