A Phase 1, Open-label, Single-dose, Multi-center, Parallel Group Study to Evaluate the Pharmacokinetics of TNO155 in Participants With Mild, Moderate, or Severe Hepatic Impairment Compared to Matched Healthy Control Participants

Novartis Pharmaceuticals0 个研究点开始时间: 2025年3月6日最近更新: 2024年2月29日

适应症

干预措施

试验速览

阶段: 1 期
状态: 撤回
发起方: Novartis Pharmaceuticals
主要终点: AUC from time zero to infinity (AUCinf) of TNO155

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记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to evaluate the effect of various degrees of hepatic impairment on plasma pharmacokinetics (PK), safety and tolerability of TNO155.

The results of this study will guide the Novartis recommendation regarding whether or not a dose adjustment may be needed when treating patients with hepatic impairment.

详细描述

This is a study to evaluate the PK of TNO155 in participants with mild, moderate or severe hepatic impairment compared to matched healthy control participants with normal hepatic function.

The study will be divided into 2 parts. Participants in the hepatic impairment groups will be staged by their respective degree of hepatic impairment (mild, moderate, or severe) according to a classification score determined at the screening visit and confirmed unchanged at the baseline visit.

Each participant in the healthy control group may be matched to 1 or more evaluable participants with hepatic impairment with respect to age (± 10 years), body weight (± 20%), sex and smoking status (smoker vs. non smoker). Each participant in the control group can be matched to participants from any hepatic impairment group but cannot be matched to more than 1 participant from the same hepatic impairment group.

All participants will be domiciled from Day -1 until Day 11. All participants should have a poststudy safety follow-up contact conducted approximately 30 days after administration of study treatment. The study will be considered complete once all the participants have finished the required assessments, dropped out, or been lost to follow-up before completing the required assessments.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Diagnostic
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 Participants must weigh at least 50 kg and no more than 120 kg and must have a body mass index (BMI) within the range of 18.0 to 38.0 kg/m2, inclusive, for healthy participants. For participants with hepatic impairment without overt ascites, the BMI should be within the range of 18.0 to 40.0 kg/m
•For participants with hepatic impairment with overt ascites, the BMI should be within the range of 18.0 to 45.0 kg/m
•Each healthy control participant must match in age (± 10 years), sex, body weight (± 20%), and smoking status to at least 1 hepatic impairment participant in Groups 2, 3 and/or
•Groups 2 to 4 •Participants with mild, moderate or severe hepatic impairment must have a Child-Pugh score clinically determined at screening and confirmed unchanged at baseline calculated as per the Child-Pugh classification in line with the hepatic impairment status of each Group

排除标准

•All Participants
•Use of drugs (prescription, non-prescription and herbal remedies such as St John's wort) known to affect CYP3A or UGT1A3, including UGT1A3 inhibitors and inducers and strong and moderate CYP3A inhibitors and inducers, within 4 weeks prior to dosing until completion of the End of Study Visit.
•Acute or chronic hepatitis B or C infection or active infection requiring therapy that will not be completed before screening.
•Left ventricular ejection fraction (LVEF) < 50% or below the institutional standard lower limit, whichever is higher, as determined by multiple gated acquisition (MUGA) scan or Trans-thoracic echocardiography (TTE) at screening or baseline.
•At screening, history of retinal vein occlusion (RVO) or presence of predisposing factors to RVO or central serous retinopathy, or any other clinically significant ophthalmologic abnormalities determined by an ophthalmologist.
•Any single parameter of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), or alkaline phosphatase (ALP) exceeding 2.5 × upper limit of normal (ULN) or total bilirubin ≥ 1.5 ULN OR any elevation above ULN of more than 1 parameter of ALT, AST, GGT, ALP, or serum bilirubin at screening or baseline.
•Impaired renal function as indicated by clinically significantly abnormal creatinine or blood urea nitrogen and/or other urea values outside local laboratory ranges or abnormal urinary constituents at screening or baseline.
•Groups 2 and 3
•Severe complications of liver disease within the preceding 3 months prior to dosing.
•Hospitalization due to liver disease within the preceding 1 month prior to dosing.
•Participant has received liver transplant at any time in the past and is on immunosuppressant therapy.
•Participants requiring paracentesis more than every 3 weeks for the management of ascites are excluded.
•Other protocol-defined inclusion/exclusion criteria may apply.

研究组 & 干预措施

Group 1 (control)

Experimental

Healthy control participants with normal hepatic function

干预措施: TNO155 (Drug)

Group 2 (score 5-6)

Experimental

Mild hepatic impairment: Child-Pugh A

干预措施: TNO155 (Drug)

Group 3 (score 7-9)

Experimental

Moderate hepatic impairment: Child-Pugh B

干预措施: TNO155 (Drug)

Group 4 (score 10-15)

Experimental

Severe hepatic impairment: Child-Pugh C. This group may be opened if allowed by the results of the interim analysis of the Groups 1 to 3.

干预措施: TNO155 (Drug)