A Phase 1, Open-label Trial to Evaluate the Pharmacokinetics and Safety Following a Single Dose of Emraclidine in Adult Participants With Mild, Moderate, and Severe Hepatic Impairment Compared With Adult Participants With Normal Hepatic Function

AbbVie3 个研究点分布在 1 个国家目标入组 38 人开始时间: 2023年6月30日最近更新: 2025年4月4日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方
入组人数: 38
试验地点: 3
主要终点: Maximum Observed Unbound Plasma Concentration (Cmax,u) of Emraclidine

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The primary purpose of this study is to assess the effect of hepatic impairment on the pharmacokinetics (PK) of emraclidine following administration of a single oral dose in participants with mild, moderate, and severe hepatic impairment relative to matched participants with normal hepatic function.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 75 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 是

入选标准

•All Participants
•Male and female participants, body mass index of ≥18.0 to 42.0 kilograms per meter square (kg/m^2), inclusive, and a total body weight ≥50 kilograms (kg) (110 pounds [lbs]).
•Additional Inclusion Criteria for Participants With Normal Hepatic Function
•Participants who are healthy, having no clinically relevant abnormalities. Have normal hepatic function.
•Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin and prothrombin time ≤ upper limit of normal (ULN) and albumin ≥ lower limit of normal (LLN) and ≤ ULN. Participants with a history of Gilbert syndrome are eligible provided direct bilirubin fraction is <20% of total bilirubin, and hemoglobin, and reticulocyte counts are all ≤ ULN.
•Additional Inclusion Criteria for Participants With Hepatic Impairment - Participants with stable hepatic impairment that meets the criteria for Class A, Class B, or Class C of the modified Child-Pugh Classification. Stable hepatic disease defined as no clinically significant change in disease status in the last 28 days prior to the screening visit.

排除标准

•For All Participants
•Any condition or surgery that could possibly affect drug absorption, including, but not limited to, bowel resections, bariatric weight loss surgery/procedures, gastrectomy, and cholecystectomy.
•Receipt of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination or booster within 7 days of planned dosing.
•Have recently been diagnosed with symptomatic coronavirus disease 2019 (COVID-19) or test positive for SARS-CoV-2 within 15 days prior to signing the informed consent form (ICF).
•Positive drug screen or a positive test for alcohol at Screening or Baseline (Check-in/Day -1) Visits.
•Use of prohibited medications prior to randomization or likely to require prohibited concomitant therapy during the trial.
•Current use of tobacco or nicotine-containing products (cigarettes, cigars, chewing tobacco, snuff, e-cigarettes, etc). Note: Light smokers (<5 cigarettes/day or equivalent) are allowed provided they abstain from the use of tobacco- or nicotine-containing products for at least 2 hours prior to PK assessments.
•Known allergy or hypersensitivity to the investigational medicinal product (IMP), closely related compounds, or any of their specified ingredients.
•Has received IMP in a clinical trial of emraclidine within 12 months of signing the ICF.
•Participants with a 12-lead ECG demonstrating any of the following at the Screening Visit and at Check-in (Day -1):
•QT interval corrected for heart rate using Fridericia's formula (QTcF) interval >470 milliseconds (ms)
•QRS interval >120 ms (unless right bundle branch block)
•PR interval >200 ms
•Left ventricular hypertrophy (LVH) with ST depressions and/or T wave inversions in leads with relatively tall R waves (ie, LVH with associated ST-T wave abnormalities)
•Type 2 second-degree or third-degree atrioventricular block
•Heart rate <45 beats per minute (bpm) or >100 bpm
•Abnormal ECG changes (such as clinically significant ST depression or elevation or T wave inversion).
•Abnormal heart rhythm (such as atrial fibrillation and atrial flutter)
•Blood pressure measurements demonstrating any of the following at the Screening Visit and/or at Check-in (Day -1):
•Supine systolic blood pressure ≥140 millimeters of mercury (mmHg) and/or diastolic blood pressure ≥90 mmHg
•Standing systolic and/or diastolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg
•Orthostatic hypotension, defined as a decrease of ≥20 mmHg in systolic blood pressure and/or ≥10 mmHg in diastolic blood pressure after at least 2 minutes of standing compared with the average of the resting supine blood pressure measurements.
•Additional Exclusion Criteria for Participants with Hepatic Impairment
•Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m^2 based on the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation at Screening or Check-in (Day -1) visits
•Acute hepatitis
•Grade ≥2 hepatic encephalopathy
•Participants who have received an organ transplant or are currently waiting for an organ transplant and are listed on the national transplant list.
•Primary biliary cholangitis or primary sclerosing cholangitis
•ALT or AST >5 × ULN or alkaline phosphatase >2 × ULN. Participants with a history of Gilbert syndrome are eligible provided direct bilirubin fraction is <20% of total bilirubin.

研究组 & 干预措施

Severe Hepatic Impairment

Experimental

Participants will receive a single oral dose of 10 milligrams (mg) emraclidine.

干预措施: Emraclidine (Drug)

Moderate Hepatic Impairment

Experimental

Participants will receive a single oral dose of 10 mg emraclidine.

干预措施: Emraclidine (Drug)

Mild Hepatic Impairment

Experimental

Participants will receive a single oral dose of 10 mg emraclidine.

干预措施: Emraclidine (Drug)

Normal Hepatic Function

Experimental

Participants will receive a single oral dose of 10 mg emraclidine.

干预措施: Emraclidine (Drug)