A PHASE 1, RANDOMIZED, OPEN-LABEL, 3-PERIOD, 4-SEQUENCE, CROSSOVER, SINGLE-DOSE STUDY TO COMPARE THE BIOAVAILABILITY OF ORALLY ADMINISTERED BOSUTINIB CAPSULES AND TO ESTIMATE THE EFFECT OF FOOD ON BOSUTINIB CAPSULE
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 32
- 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 bioavailability of a single 100 mg bosutinib capsules relative to four 25 mg capsules under fed condition in adult healthy participants and to estimate the effect of a high-fat, high-calorie meal on the bioavailability of a single 100 mg capsule of bosutinib relative to fasted condition in adults healthy participants. The comparisons will be performed using the pharmacokinetic parameters that define the rate and extend of absorption (Cmax, AUC). Statistical analyses will be performed after the administration of a single 100 mg dose under fed condition as the Reference treatment and the four 25 mg capsules as the Test treatment for the first comparison, and after administration of a single 100 mg dose under fasted condition as the Reference treatment and the 100 mg capsule under fed condition as the Test treatment for the second comparison.
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 55 years of age, inclusive, at the time of signing the informed consent document (ICD)
- •participants who are overtly healthy as determined by medical evaluation including a detailed medical history, complete physical examination, vital signs which include BP and pulse rate measurement, clinical laboratory tests, and electrocardiogram (ECG).
- •Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
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 (eg, gastrectomy, cholecystectomy).
- •History of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg,hepatitis B surface antigen (HBcAb) or hepatitis C antibody (HCVAb).
- •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 level > ULN.
研究组 & 干预措施
Treatment B: Bosutinib four 25 mg capsule after meal
Bosutinib four 25 mg capsule taken after a high-fat and high-calorie breakfast for comparison 1
干预措施: Bosutinib capsule (Drug)
Treatment A: Bosutinib 100 mg capsule after meal (active comparator)
Bosutinib 100 mg capsule taken after a high-fat and high-calorie breakfast for comparison 1
干预措施: Bosutinib capsule (Drug)
Treatment A: Bosutinib 100 mg capsule after meal (experimental)
Bosutinib 100 mg capsule taken after a high-fat and high-calorie breakfast for comparison 2
干预措施: Bosutinib capsule (Drug)
Treatment C: Bosutinib 100 mg capsule after fasting
Bosutinib 100 mg capsule taken after an overnight fast of at least 10 hours for comparison 2
干预措施: Bosutinib (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 for Cmax (Tmax) of 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) of 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) of 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 Elimination Half-Life (t1/2) of 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 (Without Regard to Baseline Abnormality)(On Days 4, 5, 7 of Periods 1 and 2 for all participants, on Period 3 Days 4, 5, 7 for participants who were assigned to treatment sequences A=>B=>C and B=>A=>C, and at early termination/discontinuation (if applicable))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(Post first dose on Period 1 Day 1 up to 28 days post the last dose of study intervention (up to a maximum of 75 days))