A Phase 1, Open-Label, Single-Dose Study to Evaluate the Effect of Hepatic Impairment on the Pharmacokinetics of Erdafitinib
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 26
- 试验地点
- 2
- 主要终点
- Maximum Observed Plasma Concentration (Cmax)
研究概览
简要总结
The primary purpose of the study is to characterize the single dose pharmacokinetic of erdafitinib in participants with impaired hepatic function relative to 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
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Man or woman must have a clinically stable hepatic function as confirmed by the serum bilirubin and transaminase levels measured during screening and those measured on Day -1
- •If a woman (a) must not be of childbearing potential postmenopausal or surgically sterile (b) must agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 3 months after the study drug administration
- •If a woman who is considered surgically sterile but not postmenopausal, must have a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test at screening (exemptions: pregnancy test not required in female participants with prior hysterectomy or prior bilateral oophorectomy)
- •If a woman, must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 3 months after the study drug administration
- •Participants with hepatic impairment must meet the Child-pug classification for mild, moderate or severe hepatic impairment and must have stable hepatic function
排除标准
- •History or current evidence of ophthalmic disorder, such as central serous retinopathy (CSR) or retinal vein occlusion, active wet age related macular degeneration, diabetic retinopathy with macular edema, uncontrolled glaucoma, corneal pathology such as keratitis, keratoconjunctivitis, keratopathy, corneal abrasion, inflammation or ulceration
- •Any surgical or medical condition that may alter the absorption, metabolism, or excretion of the study drug (example, gastrectomy, Crohn's disease etc), with the exception of hepatic impairment
- •History of drug abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-V) criteria within 6 months before screening or positive test result(s) for drugs of abuse (including barbiturates, opiates, cocaine, cannabinoids, amphetamines, hallucinogens, and benzodiazepines) at screening and on Day -1
- •Known allergy to the study drug or any of the excipients of the formulation (Physical Description of Study Drug[s], for a list of excipients)
- •Donated blood or blood products or had substantial loss of blood (more than 500 milliliter [mL]) within 3 months before study drug administration or intention to donate blood or blood products during the study
研究组 & 干预措施
Cohort 1: Normal Hepatic Function
Participants with normal hepatic function will receive 6 milligram (mg) erdafitinib as a single oral dose under fasted conditions on Day 1.
干预措施: Erdafitinib (Drug)
Cohort 2: Mild Hepatic Impairment
Participants with mild hepatic impairment (Child-Pugh score of 5 or 6) will receive 6 mg erdafitinib as a single oral dose under fasted conditions on Day 1.
干预措施: Erdafitinib (Drug)
Cohort 3: Moderate Hepatic Impairment
Participants with moderate hepatic impairment (Child-Pugh score of 7 to 9) will receive 6 mg erdafitinib as a single oral dose under fasted conditions on Day 1.
干预措施: Erdafitinib (Drug)
Cohort 4: Severe Hepatic Impairment
Participants with severe hepatic impairment (Child-Pugh score of 10 to 15) will only be enrolled to receive appropriate dose level of erdafitinib after review of preliminary safety and pharmacokinetic (PK) data from the mild and moderate hepatic impairment cohorts.
干预措施: Erdafitinib (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax)
时间窗: Up to 21 days
Cmax is the maximum observed plasma concentration.
Terminal Elimination Half-life (t1/2term, Lambda)
时间窗: Up to 21 days
t1/2term, Lambda is elimination half-life associated with the terminal slope (Lambda\[Z\]) of the semi logarithmic drug concentration-time curve, calculated as 0.693/Lambda(Z).
Apparent Volume of Distribution (Vd/F)
时间窗: Up to 21 days
Vd/F is apparent volume of distribution after extravascular administration, uncorrected for absolute BA.
Area Under Plasma Concentration-Time Curve (AUC)
时间窗: Up to 21 days
AUC is area under plasma concentration-time curve.
Total Plasma Clearance (CL/F)
时间窗: Up to 21 days
CL/F is total plasma clearance of drug after extravascular administration, uncorrected for absolute bioavailability (BA), calculated as Dose/AUC (0-infinity).
Time to Reach the Maximum Observed Plasma Concentration (Tmax)
时间窗: Up to 21 days
Tmax is the time to reach maximum observed plasma concentration.
次要结局
- Number of Participants with Adverse Events as a Measure of Safety and Tolerability(Approximately 50 days)