A Phase I, Open-label and Single-dose Study to Evaluate the Pharmacokinetics and Safety of a Single 40 mg Oral Dose of ABL001 (Asciminib) in Subjects With Impaired Renal Function Compared to Matched Control Subjects With Normal Renal Function
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Pharmacokinetics: Plasma concentration of asciminib by AUClast
研究概览
简要总结
The purpose of this study is to characterize the pharmacokinetics (PK) and safety profile of asciminib following a single oral dose in adult subjects with renal impairment compared to a matched group of healthy subjects with normal renal function.
The results will determine whether or not a dose adjustment should be recommended when treating patients with asciminib who have impaired renal 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
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or sterile / post-menopausal female
- •BMI between 18 and 36 kg/m2, body weight greater than or equal to 50 kg and no more than 120 kg
- •Adequate venous access for blood sampling
- •For healthy volunteers: subject must be matched to at least one renal impaired subject by age (+/- 10 years), body weight (+/- 20%) and gender
- •For renal impaired subjects: documented stable renal disease without evidence of progressive decline in renal function (stable renal disease is defined as no significant change, such as, stable aGFR < 90, for 12 weeks prior to study entry)
排除标准
- •women of child-bearing potential / pregnant / nursing
- •contraindication or hypersensitivity to any drug or metabolites from similar class as asciminib or to any excipients of the study drug
- •cardiac or cardiac repolarization abnormality
- •history of psychiatric illness within the past 2 years
- •history of acute or chronic pancreatitis
- •subject on dialysis
- •smokers (use of tobacco products in the previous 3 months) and not willing to abstain from using tobacco during the study
- •any surgical or medical condition altering the absorption, distribution, metabolism or excretion of drug
- •history of immunodeficiency diseases, including a positive Human Immunodeficiency Virus (HIV) test result at screening
- •chronic infection with Hepatitis B virus (HBV) or Hepatitis C virus (HCV) at screening
- •donation or loss of 400 mL or more of blood or plasma within 8 weeks prior to dosing or other amount considered to compromise the health of the subject if previous history of anemia exists
- •use of the following drugs within 28 days prior to dosing: drugs that prolong the QT interval; CYP3A4 inhibitors and inducers; BCRP, UGT and PgP inhibitors and inducers
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
Mild renal impairment
subjects with mild renal impairment
干预措施: Asciminib (Drug)
Normal renal function
healthy volunteers with normal renal function
干预措施: Asciminib (Drug)
Severe renal impairment
subjects with severe renal impairment
干预措施: Asciminib (Drug)
Moderate renal impairment
subject with moderate renal impairment
干预措施: Asciminib (Drug)
结局指标
主要结局
Pharmacokinetics: Plasma concentration of asciminib by AUClast
时间窗: pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose
The AUC from time zero to the last measurable concentration sampling time (tlast) (ng\*h/mL)
Pharmacokinetics: Plasma concentration of asciminib by AUCinf
时间窗: pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose
The AUC from time zero to infinity (ng\*h/mL)
Pharmacokinetics: Plasma concentration of asciminib by Cmax
时间窗: pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose
The maximum (peak) observed plasma, blood, serum, or other body fluid drug concentration after single dose administration (ng/mL)
Pharmacokinetics: Clearance of asciminib from plasma by CL/F
时间窗: pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose
The total body clearance of drug from the plasma (L/h)
次要结局
- Asciminib PK parameters unbound AUClast (AUClast)u and unbound AUCinf (AUCinf)u based on unbound fraction in plasma(pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose)
- Asciminib PK parameters unbound Cmax (Cmax)u based on unbound fraction in plasma(pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose)
- Asciminib secondary PK parameters Tmax, T1/2(pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose)
- Asciminib secondary PK parameter AUC0-72h(pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose)
- Asciminib secondary PK parameters Vz/F(pre-dose (0 hour) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48 and 72 hours post-dose)
- Percentage of participants with plasma protein binding as expressed by unbound fraction in plasma(2 hours post-dose)