A PHASE 1, OPEN-LABEL, RANDOMIZED, 3-PERIOD, 6-SEQUENCE, CROSSOVER STUDY TO EVALUATE THE BIOAVAILABILITY OF BOSUTINIB ADMINISTERED AS CAPSULE CONTENTS MIXED WITH APPLESAUCE OR YOGURT RELATIVE TO INTACT CAPSULES IN HEALTHY PARTICIPANTS UNDER FED CONDITION
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Bosutinib
研究概览
简要总结
This study is intended to estimate the relative bioavailability of a single 500 mg dose of bosutinib when administered as capsule contents mixed with applesauce or yogurt to intact capsules under fed condition in adult healthy participants. The comparisons will be performed using the pharmacokinetic parameters that define the rate and extent of absorption, those are Cmax and AUC. Statistical analyses will be performed comparing these parameters calculated after administration of a single 500 mg dose with the intact capsule formulation (100 mg x 5) as the Reference treatment and the capsule contents mixed with applesauce or yogurt (100 mg x 5) as the Test treatments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Female participants of non childbearing potential and/or male participants must be 18 to 54 years of age, inclusive, at the time of signing the informed consent document (ICD).
- •Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.
排除标准
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, dermatological, or allergic disease.
- •Any condition possibly affecting drug absorption.
- •Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary:
- •estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) < 90 mL/min/1.73 m2;
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level > upper limit of normal (ULN);
- •Serum (total and direct) bilirubin level > ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is <= ULN;
- •Amylase and lipase levels > ULN.
研究组 & 干预措施
Bosutinib capsule contents mixed with applesauce
Bosutinib capsule contents mixed with applesauce to healthy participants
干预措施: Bosutinib capsule (Drug)
Bosutinib capsule contents mixed with yogurt
Bosutinib capsule contents mixed with yogurt to healthy participants
干预措施: Bosutinib capsule (Drug)
Bosutinib intact capsules
Bosutinib intact capsules to healthy participants
干预措施: Bosutinib capsule (Drug)
结局指标
主要结局
Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) for Bosutinib
时间窗: Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose
AUCinf was calculated as \[AUClast+(Clast\*/kel)\], where AUClast is the area under the plasma concentration-time profile from time 0 to the time of the Clast, Clast is the last quantifiable concentration, Clast\* is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. The geometric coefficient of variation was reported as percentage.
Maximum Observed Plasma Concentration (Cmax) for Bosutinib
时间窗: Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose
Cmax was the maximum observed plasma concentration. The geometric coefficient of variation was reported as percentage.
次要结局
- Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Bosutinib(Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose)
- Time to Reach Maximum Observed Plasma Concentration (Tmax) for Bosutinib(Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose)
- Apparent Clearance After Oral Dose (CL/F) for Bosutinib(Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose)
- Apparent Volume of Distribution After Oral Dose (Vz/F) for Bosutinib(Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose)
- Terminal Phase Half-life (t½ ) for Bosutinib(Predose (0 hour) and at 1, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72, 96, and 144 hours post bosutinib dose)
- Number of Participants With Laboratory Abnormalities(Post first dose and up to Day 7 in Period 3, or at early termination/discontinuation.)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs), Severe Adverse Events (AEs), and Serious Adverse Events (SAEs)(Up to 12 weeks)