A Phase 1, Open-Label, Fixed-Sequence, Drug-Drug Interaction Study to Evaluate the Effects of Tucatinib of the Pharmacokinetics of Metformin in Healthy Male and Female Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Seagen Inc.
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximum observed plasma concentration (Cmax) of metformin
研究概览
简要总结
This study is being done to look at how tucatinib might affect the way another drug (metformin) works. It will look at healthy volunteers and how tucatinib affects how the body absorbs metformin. This will help us find out whether tucatinib is safe to give together with metformin. The study will also look at how tucatinib affects how the kidneys work.
详细描述
This is a single center, fixed-sequence, drug-drug interaction study to assess the effects of multiple oral doses of tucatinib on the pharmacokinetics of a single oral dose of metformin in healthy subjects. The primary objective of the study is to assess the effects of tucatinib on the single-dose PK of metformin. Secondary objectives of the study are to (1) assess the safety and tolerability of metformin when coadministered with tucatinib and (2) assess the effects of tucatinib on renal function using iohexol as glomerular filtration rate (GFR) marker.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy status, as defined by the absence of evidence of any clinically significant findings
- •Males must agree to use a barrier method of birth control and not donate sperm during study plus 30 days after last dose of study drug
- •Weight of ≥60kg
- •Body mass index between 18.0 and 32.0 kg/m² (inclusive)
- •Ability to abstain from alcohol-, caffeine-, and xanthine-containing food and beverages from 48 hours prior to admission through study discharge
- •All nonregular medication (including over-the-counter medication, health supplements, and herbal remedies) must be stopped at least 28 days prior to admission
排除标准
- •Females who are of childbearing potential or lactating
- •Males with female partners who are pregnant, lactating, or planning to become pregnant within 30 days of the study
- •Use of any investigational drug or device within 30 days of study start
- •Use of tobacco products within 21 days prior to admission
- •Routine or chronic use of more than 3 grams of acetaminophen daily
- •Strenuous activity, sunbathing, and contact sports within 72 hours prior to first admission and for the duration of the study
- •Blood transfusion within 90 days of study drug administration
- •History of alcoholism or drug abuse within 2 years
- •History of alcohol consumption exceeding 7 drinks/week for female participants or 14 drinks/week for male subjects
- •History of donation of more than 450 mL of blood within 60 days prior to dosing, or planned donation before 30 days have elapsed since intake of study drug
- •Plasma or platelet donation within 7 days of initial study drug administration
- •Positive screening test for Hepatitis B, Hepatitis C, or HIV 1 or 2 (human immunodeficiency virus)
- •Acute or chronic metabolic acidosis, including diabetic ketoacidosis
- •Renal disease or dysfunction as suggested by serum creatinine levels or abnormal creatinine clearance
研究组 & 干预措施
Tucatinib plus metformin
Tucatinib administered twice daily on Days 2-8. Metformin administered as a single dose on Days 1 and 8. Iohexol administered via IV push on Days 1 and 8
干预措施: Tucatinib (Drug)
Tucatinib plus metformin
Tucatinib administered twice daily on Days 2-8. Metformin administered as a single dose on Days 1 and 8. Iohexol administered via IV push on Days 1 and 8
干预措施: Metformin (Drug)
Tucatinib plus metformin
Tucatinib administered twice daily on Days 2-8. Metformin administered as a single dose on Days 1 and 8. Iohexol administered via IV push on Days 1 and 8
干预措施: Iohexol (Drug)
结局指标
主要结局
Maximum observed plasma concentration (Cmax) of metformin
时间窗: Up to 9 days
Time to maximum observed plasma concentration (tmax) of metformin
时间窗: Up to 9 days
Area under the plasma concentration-time curve from time 0 to the last available measurement (AUC0-last) of metformin
时间窗: Up to 9 days
Area under the plasma concentration time curve to time 0 extrapolated to infinity (AUC0-inf) of metformin
时间窗: Up to 9 days
Apparent volume of distribution (V2/F) of metformin
时间窗: Up to 9 days
Half-life (t1/2) of metformin
时间窗: Up to 9 days
Oral clearance (CL/F) of metformin
时间窗: Up to 9 days
次要结局
- Glomerular Filtration Rate (GFR) as measured by iohexol plasma clearance(Up to 8 days)
- Incidence of adverse events (as assessed by AE assessments, clinical laboratory tests, physical examinations, vital signs measurements, and 12-lead electrocardiogram)(Up to 16 days)