临床试验/NCT07300189

NCT07300189招募中1 期

A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of TLC-1180 in Healthy Subjects

OrsoBio, Inc1 个研究点分布在 1 个国家目标入组 332 人开始时间: 2025年10月20日最近更新: 2026年8月21日

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方: OrsoBio, Inc
入组人数: 332
试验地点: 1
主要终点: Incidence of TLC-1180 treatment-emergent adverse events

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

This phase 1 study is designed to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of TLC-1180 after single- and multiple-ascending doses in healthy subjects.

详细描述

The primary objectives are to assess the safety, tolerability, and plasma PK of TLC-1180 in healthy subjects. The exploratory objective is to evaluate the PD of TLC-1180 in healthy subjects. This study is comprised of three parts: Part A (single-ascending dose), Part B (adaptive multiple-ascending dose), and Part C (adaptive single-ascending dose). Up to 72, 100, and 160 healthy subjects will be recruited in Parts A, B, and C, respectively.

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Sequential
主要目的: Treatment
盲法: Double (Participant, Investigator)

入排标准

年龄范围: 18 Years 至 55 Years（Adult）
性别: All
接受健康志愿者: 是

入选标准

•Non-smoking, healthy male or female subject between 18 and 55 years of age, inclusive
•Body mass index from 19 to 35 kg/m2, inclusive
•Estimated glomerular filtration rate ≥ 80 mL/min
•Normal liver biochemistry tests
•Screening laboratory evaluations (hematology, chemistry, and urinalysis) must fall within the normal range of the local laboratory's reference ranges unless the results have been determined by the investigator to have no clinical significance
•Subject must have either a normal 12-lead electrocardiogram (ECG) or one with abnormalities that are considered clinically insignificant by the investigator
•Females of childbearing potential must have a negative pregnancy test at Screening and clinic admission
•Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception
•Must, in the opinion of the investigator, be in good health based upon medical history and physical examination, including vital signs

排除标准

•Pregnant or lactating subjects
•Subjects who have any serious or active medical or psychiatric illness (including depression) that, in the opinion of the investigator, would interfere with the subject's treatment, assessment, or compliance with the protocol
•Subjects who have received any investigational compound within 30 days or 5 half-lives, whichever is longer, prior to study drug dosing
•Current alcohol abuse that is judged by the investigator to potentially interfere with the subject's compliance or safety
•Current substance abuse that is judged by the investigator to potentially interfere with the subject's compliance or safety
•A positive test result for human immunodeficiency virus (HIV-1) antibody, hepatitis B (HBV) surface antigen, or hepatitis C (HCV) antibody
•Subjects who have taken any prescription medications or over-the-counter medications, including herbal products, within 28 days prior to start of study drug dosing, with the exception of vitamins, acetaminophen (paracetamol), ibuprofen, and/or hormonal contraceptive medications
•Subjects who have been treated with systemic steroids, immunosuppressant therapies, or chemotherapeutic agents within 3 months prior to Screening or expected to receive these agents during the study (e.g., corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies)
•Medical history of serious skin disease in the opinion of the investigator, such as but not limited to rash, food allergy, eczema, psoriasis, or urticaria
•Medical history of drug sensitivity or drug allergy (such as anaphylaxis or hepatoxicity)
•Presence or history of cardiovascular disease, including significant cardiovascular disease (including a history of myocardial infarction based on ECG and/or clinical history), history of cardiac conduction abnormalities (including any history of ventricular tachycardia), congestive heart failure, cardiomyopathy with left ventricular ejection fraction < 40%, a family history of Long QT Syndrome, or unexplained death in an otherwise healthy individual between the ages of 1 and 30 years
•Syncope, palpitations, or unexplained dizziness
•Implanted defibrillator or pacemaker
•Medical history of liver disease, including but not limited to alcoholic liver disease, autoimmune disorders (e.g., primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency)
•History of rhabdomyolysis
•Severe peptic ulcer disease, gastroesophageal reflux disease, or other gastric acid hypersecretory conditions
•History of medical or surgical treatment that permanently alters intestinal absorption (e.g., gastric or intestinal surgery)
•Subjects who have received vaccination for COVID-19 within 14 days of Admission
•Note: Other protocol defined Inclusion/Exclusion criteria may apply.

研究组 & 干预措施

Oral Solution

Experimental

Oral solution of TLC-1180

干预措施: Placebo Oral Solution (Other)

Oral Solution

Experimental

Oral solution of TLC-1180

干预措施: TLC-1180 Oral Solution (Drug)

Tablet

Experimental

Tablet formulation of TLC-1180

干预措施: Placebo Tablet (Other)

Tablet

Experimental

Tablet formulation of TLC-1180

干预措施: TLC-1180 Tablet (Drug)

结局指标

主要结局

Incidence of TLC-1180 treatment-emergent adverse events

时间窗: Through study completion: Day 365 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study

Adverse events (AEs) - severity of the AEs will be graded using the Common Terminology Criteria for AE (CTCAE) (v5.0). The relationship between AEs and the study drug will be indicated as related or not related.

PK of TLC-1180 AUC

时间窗: Through study completion: Day 365 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study

Area under the concentration-time curve

PK of TLC-1180 Cmax

时间窗: Through study completion: Day 365 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study

Maximum plasma concentration

PK of TLC-1180 tmax

时间窗: Through study completion: Day 365 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study

Time to reach Cmax

PK of TLC-1180 t1/2

时间窗: Through study completion: Day 365 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study

Half-life

PK of TLC-1180 CL/F

时间窗: Through study completion: Day 365 (Parts A, C); Day 28 (Parts B, C); Day 39 (Part D) of the study

Apparent clearance, calculated as dose/AUC0-inf

Incidence of TLC-1180 treatment-emergent adverse events