An Open-label, Multiple-dose, Adaptive Design Study to Evaluate the Effects of Hepatic Impairment on the Pharmacokinetics of Relacorilant
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Area under the concentration-time curve of plasma relacorilant from time zero to the end of the dosing interval (24 hours) (AUCt)
研究概览
简要总结
The primary objective of this multiple-dose, adaptive design study is to evaluate the effect of hepatic impairment on the pharmacokinetics (PK) of relacorilant relative to healthy matched control male and female subjects (Part 1).
详细描述
If an obvious effect of moderate hepatic impairment on exposure to relacorilant is observed in Part 1, optional Part 2 of the study will be conducted. In Part 2, the effect of mild hepatic impairment on the PK of relacorilant will be evaluated, using control data from the same healthy control subjects who were matched to the subjects in Part 1.
Secondary objectives of the study are 1) evaluation of the effect of hepatic impairment on the PK of relacorilant metabolites, and 2) evaluation of safety and tolerability of relacorilant on healthy subjects and those with hepatic impairment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 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
- •Able to understand the purpose and risks of the study and is willing and able to adhere to scheduled visits, treatment plans, laboratory tests, and other study evaluations and procedures
- •Provide written informed consent before any study-specific procedure is performed
- •Male or a nonpregnant, nonlactating female judged to be in good health, except for allowance of health conditions consistent with hepatic impairment
- •Body mass index (BMI) between 18 and 32 kg/m^2, inclusive, and a body weight more than 50 kg (110 pounds)
- •Estimated glomerular filtration rate (eGFR) ≥80 mL/minute/1.73 m^2
- •Suitable veins for multiple venipuncture/cannulation
- •Agrees to limit smoking or use of tobacco or nicotine-containing products to less than 5 cigarettes or uses per day
- •Willing to comply with study restrictions as described in the protocol
- •Female subject is of either nonchildbearing potential (ie, postmenopausal or permanently sterilized) or uses highly effective contraception with low user-dependency, as described in the protocol.
- •Subjects with normal hepatic function must also satisfy the following inclusion criteria:
- •Clinical laboratory results within the reference range at Screening and Day -1, unless considered not clinically significant by the Principal Investigator
- •Negative screening results for hepatitis B surface antigen, hepatitis C virus antibody, and HIV antibodies.
- •Subjects with moderate or mild hepatic impairment must also satisfy the following inclusion criteria:
- •Documented parenchymal hepatic disease
- •Liver dysfunction of moderate (Child-Pugh Class B [score of 7 to 9]; Part 1) or mild (Child-Pugh Class A [score of 5 to 6]; Part 2) severity
- •Stable hepatic impairment defined as no clinically significant change in disease status within the last 30 days
- •On a stable dose of medication and/or treatment regimen at least 2 weeks before study drug dosing
- •If a subject has nonhepatic abnormal clinical laboratory results, these results are considered not clinically relevant by the Principal Investigator (or designee) and the medical monitor.
排除标准
- •An employee or immediate family member of the Clinical Research Unit (CRU) or the Sponsor
- •Has been previously enrolled in any study of relacorilant
- •Has multiple clinically significant drug allergies or is allergic to any of the components of relacorilant
- •Has a condition that could be aggravated by excessive glucocorticoid receptor antagonism. Subjects with inactive seasonal hay fever or childhood asthma may be included.
- •Has a history of malabsorption syndrome or previous gastrointestinal surgery that could affect drug absorption or metabolism
- •Has Gilberts syndrome
- •Has current or previous (within a 1-year period) alcohol or substance abuse and/or dependence
- •Has evidence of acute viral hepatitis in the 3 calendar months before the first dose of study drug
- •In the 2 calendar months before the first dose of study drug, subject has: donated/lost blood or plasma in excess of 400 mL, or received an investigational drug
- •Has a positive result for alcohol or drugs of abuse at Screening or upon admission to the CRU
- •Has clinically relevant abnormal vital signs, physical examination, laboratory tests, or 12-lead ECG findings at Screening and/or before the first dose of study drug, other than those associated with chronic hepatic impairment
- •Has taken any prohibited prior medication, as described in the protocol
- •Has any other condition that might increase the risk to the individual or decrease the chance of obtaining satisfactory data, as assessed by the Principal Investigator.
- •Additional exclusion criteria for subjects with moderate or mild hepatic impairment:
- •Has hepatic encephalopathy of Grade 2 that has not been controlled with medication for the previous 3 calendar months before Screening or of Grade 3 or higher within the previous 3 calendar months before Screening, regardless of use of medication for the treatment of hepatic encephalopathy
- •Has a history of liver transplantation, hepatocellular carcinoma, portosystemic shunt, or acute liver disease (eg, caused by infection or drug toxicity).
研究组 & 干预措施
No Hepatic Impairment
Subjects with no hepatic impairment will receive relacorilant 300 mg once daily on Days 1 through 10.
干预措施: Relacorilant (Drug)
Moderate Hepatic Impairment
Subjects with moderate hepatic impairment (Child-Pugh Class B) will receive relacorilant 300 mg once daily on Days 1 through 10.
干预措施: Relacorilant (Drug)
Mild Hepatic Impairment
Subjects with mild hepatic impairment (Child-Pugh Class A) will receive relacorilant 300 mg once daily on Days 1 through 10.
干预措施: Relacorilant (Drug)
结局指标
主要结局
Area under the concentration-time curve of plasma relacorilant from time zero to the end of the dosing interval (24 hours) (AUCt)
时间窗: Predose and at serial time points up to 24 hours after dosing on Day 10
Maximum concentration of plasma relacorilant during the dosing interval (Cmax)
时间窗: Predose and at serial time points up to 24 hours after dosing on Day 10
次要结局
- AUCt of relacorilant plasma metabolites(Predose and at serial time points up to 24 hours after dosing on Day 10)
- Number of subjects with one or more treatment-emergent adverse events(Up to Day 20)
- Number of subjects with one or more treatment-emergent adverse events by severity(Up to Day 20)
- Cmax of relacorilant plasma metabolites(Predose and at serial time points up to 24 hours after dosing on Day 10)