An Open-label, Non-randomized, Single-dose, Parallel-group, Safety, Tolerability, and Pharmacokinetic Study of Tucatinib Administered at 300 mg in Fasted, Hepatically-impaired Male and Female Subjects and Fasted Matched-control Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Seagen Inc.
- 入组人数
- 37
- 试验地点
- 4
- 主要终点
- Time of maximum observed concentration (Tmax)
研究概览
简要总结
The investigators are doing this study to find out if tucatinib is safe for patients with liver problems. This study will look at participants with mild, moderate, and severe liver problems. For each participant with liver problems who takes part, a matching healthy participant who is of similar age, similar body mass index (BMI), and of the same sex will also take part. The study will look at how the drug affects healthy participants compared to participants with liver problems.
详细描述
This study is being conducted to provide information to develop dosing recommendations for tucatinib in subjects with hepatic impairment. The current study will be carried out in subjects with hepatic impairment according to 3 different Child-Pugh (CP) categories (Mild, Moderate, and Severe impairment), and in matched-control healthy subjects. The minimum number of matched-control healthy subjects will be enrolled in order to ensure that each hepatically-impaired subject has a healthy match. Each matched-control healthy subject will be enrolled following the enrollment of a Mild and/or Moderate and/or Severe hepatic impairment subject and will be matched by age (+/- 10 years), by BMI (+/- 20%), and by sex to the enrolled hepatic impairment subject(s). Each healthy subject may be matched with up to 1 subject within each hepatic impairment group. Based on these criteria, with 3 cohorts of 8 hepatically-impaired subjects enrolled in the study, the number of healthy control subjects required to be enrolled will be at least 8 and not more than 24.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •In good general health, except for additional inclusion criteria related to subjects with hepatic impairment
- •Within body mass index (BMI) range of 18 to 37 kg/m^2 (inclusive)
- •Males capable of fathering a child must agree to use contraception from check in through 90 days after dose administration
- •Females must be of nonchildbearing potential
- •Able to understand and provide written informed consent
- •Able to comply with all study procedures, including the 3-night stay at the clinical site and follow-up phone call
- •Healthy subjects only: matched to subjects with Mild and/or Moderate and/or Severe hepatic impairment in sex, age (+/- 10 years), and BMI (+/- 20%).
- •Hepatic impairment subjects only: considered to have Mild, Moderate, or Severe hepatic impairment that has been clinically stable for at least 1 month
- •Hepatic impairment patients only: currently on stable medication regimen
排除标准
- •Subjects with at-rest vital signs outside of the following ranges: heart rate (40 to 120 bpm), systolic blood pressure (90 to 150 mmHg), diastolic blood pressure (40 to 95 mmHg)
- •Clinically significant abnormal laboratory values or physical examination findings
- •Evidence/history of long QT syndrome
- •Use of drugs/substances known to be inhibitors or inducers of CYP3A4 or CYP2C8 enzyme within 30 days
- •Consumption of foods or beverages containing poppy seeds, grapefruit, or Seville oranges within 7 days of check-in
- •Consumption of alcohol-, citric acid-, caffeine-, or xanthine-containing foods or beverages within 48 hours prior to check in
- •Subjects with known alcohol and/or drug abuse within 1 month prior to check in
- •History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance
- •History of congenital nonhemolytic hyperbilirubinemia
- •History of stomach or intestinal surgery that would potentially alter absorption and/or excretion of orally administered drugs
- •Prior doses of tucatinib
- •Prior dose of any investigational drug within the past 30 days or 5 half-lives
研究组 & 干预措施
Group 1: Healthy
Match-controlled healthy subjects with normal hepatic function
干预措施: Tucatinib (Drug)
Group 2: Mild Hepatic Impairment
Subjects with Mild hepatic impairment (Child-Pugh Class A, score of 5 or 6)
干预措施: Tucatinib (Drug)
Group 3: Moderate Hepatic Impairment
Subjects with Moderate hepatic impairment (Child-Pugh Class B, score of 7 to 9)
干预措施: Tucatinib (Drug)
Group 4: Severe Hepatic Impairment
Subjects with Severe hepatic impairment (Child-Pugh Class C, score of 10 to 14)
干预措施: Tucatinib (Drug)
结局指标
主要结局
Time of maximum observed concentration (Tmax)
时间窗: Up to 48 hours
PK endpoint of tucatinib
Maximum observed concentration (Cmax)
时间窗: Up to 48 hours
Pharmacokinetic (PK) endpoint of tucatinib
Percentage extrapolation for AUC (%AUCextrap)
时间窗: 48 hours
PK endpoint of tucatinib
Apparent terminal elimination half-life (t½)
时间窗: Up to 48 hours
PK endpoint of tucatinib
Mean residence time (MRT)
时间窗: Up to 48 hours
PK endpoint of tucatinib
Apparent terminal elimination rate constant (λz)
时间窗: Up to 48 hours
PK endpoint of tucatinib
Apparent total clearance
时间窗: Up to 48 hours
PK endpoint of tucatinib
Apparent volume of distribution during the terminal phase
时间窗: Up to 48 hours
PK endpoint of tucatinib
Area under the concentration-time curve (AUC) from time 0 to the last quantifiable concentration (AUC[0-t])
时间窗: Up to 48 hours
PK endpoint of tucatinib
AUC from time 0 to infinity (AUC[0-inf])
时间窗: Up to 48 hours
PK endpoint of tucatinib
次要结局
- AUC[0-t](Up to 48 hours)
- Cmax(Up to 48 hours)
- %AUCextrap(Up to 48 hours)
- Tmax(Up to 48 hours)
- Incidence of adverse events (AEs)(Up to 9 days)
- (AUC[0-inf])(Up to 48 hours)
- λz(Up to 48 hours)
- t½(Up to 48 hours)
- MRT(Up to 48 hours)