Open-label, Randomized, 3-period, 3-treatment Crossover, Bioequivalence Study Comparing Dasatinib (BMS-354825) Liquid Formulation and the Dispersed Tablet Formulation Relative to the Reference Tablet Formulation in Health Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 141
- 试验地点
- 1
- 主要终点
- Maximum Observed Concentration (Cmax) of Dasatinib
研究概览
简要总结
The purpose of the study is to compare the blood levels of dasatinib in healthy participants who received tablet formulation with those of healthy participants who received liquid and tablet-dispersed formulations of the drug.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 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
- •Healthy participants, defined as having no clinically relevant deviation from normal in medical history, physical examination, electrocardiogram (ECG) findings, and clinical laboratory tests findings.
- •Body mass index of 18 to 32 kg/m^2, inclusive
- •Age from 18 to 55 years
- •Men and women who were not of childbearing potential (ie, who were postmenopausal or surgically sterile)
- •All women must have had a negative serum or urine pregnancy test result(minimum sensitivity 25 IU/L or equivalent units of human chorionic gonadotropin) at screening and within 24 hours prior to dosing with study drug
- •Women must not have been breastfeeding
- •Sexually active fertile men with female partners of childbearing potential were required to abide by the requirement to use effective birth control for the entire study and for 90 days after the date of last treatment
- •Men must have agreed not to donate sperm for the entire study and for 90 days after the day of last study treatment
- •Participants must have agreed not to make blood donations, including red blood cells, plasma, platelets, or whole blood, for the entire study and for 8 weeks after the day of last study treatment
排除标准
- •Any significant acute or chronic medical illness
- •Current or recent (within 3 months of study drug administration) disease of the gastrointestinal (GI) tract that may impact drug absorption and may affect pharmacokinetics of the study drugs or any GI tract surgery that may impact drug absorption
- •Any major surgery, as determined by the investigator, within 4 weeks of dosing in Period 1
- •Blood transfusion within 4 weeks of study drug administration
- •Donation of >400 mL of blood within 8 weeks prior to study dosing or donation of plasma within 4 weeks prior to study dosing
- •Inability to tolerate oral medication
- •Inability to tolerate orange juice
- •Inability to undergo venipuncture and/or tolerate venous access
- •Use of tobacco or nicotine-containing products within 6 months prior to check-in, or positive nicotine test at screening and/or check-in
- •Consumption of more than 3 cups of coffee or other caffeine-containing products a day, or 5 cups of tea a day
- •Recent (within 6 months of study drug administration) drug or alcohol abuse
- •Positive blood screen for hepatitis C antibody; hepatitis B surface antigen; and HIV-1, HIV-2, or HIV antibody
- •History of any significant drug allergy or asthma
- •Evidence of organ dysfunction or any clinically relevant deviation from normal in physical examination, ECG findings, vital signs, or clinical laboratory test findings.
- •Any of the following on 12-lead ECG prior to study drug administration, confirmed by repeat ECG:
- •PR ≥210 ms
- •QRS ≥120 ms
- •QT ≥500 ms
- •QTcF ≥450 ms
研究组 & 干预措施
Dasatinib, 100 mg as tablets + water
Treatment A. Participants were randomized to and received treatment in 1 of 6 sequences (ABC, ACB, BCA, BAC, CAB, or CBA), administered over 3 1-day treatment periods (Days 1, 5, and 9), with treatment changing to next in the sequence at start of each new period. A 3-day washout period followed treatment periods 1 and 2.
干预措施: Dasatinib as tablets (Drug)
Dasatinib, 100 mg as liquid + water
Treatment B. Participants were randomized to and received treatment in 1 of 6 sequences (ABC, ACB, BCA, BAC, CAB, or CBA), administered over 3 1-day treatment periods (Days 1, 5, and 9), with treatment changing to next in the sequence at start of each new period. A 3-day washout period followed treatment periods 1 and 2.
干预措施: Dasatinib as liquid (Drug)
Dasatinib, 100 mg as tablets in orange juice + water
Treatment C. Participants were randomized to and received treatment in 1 of 6 sequences (ABC, ACB, BCA, BAC, CAB, or CBA), administered over 3 1-day treatment periods (Days 1, 5, and 9), with treatment changing to next in the sequence at start of each new period. A 3-day washout period followed treatment periods 1 and 2.
干预措施: Dasatinib as dispersed tablets (Drug)
结局指标
主要结局
Maximum Observed Concentration (Cmax) of Dasatinib
时间窗: Days 1-2, Days 5-6, and Days 9-10
Single-dose pharmacokinetic parameters, including Cmax, were derived using noncompartmental methods from plasma dasatinib concentration-time data.
Area Under the Plasma Concentration-time Curve From Zero to the Last Time of the Last Quantifiable Concentration (AUC[0-T])of Dasatinib
时间窗: Days 1-2, Days 5-6, and Days 9-10
Single-dose pharmacokinetic, such as AUC(0-T),parameters were derived using noncompartmental methods from plasma dasatinib concentration-time data.
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC[0-INF]) of Dasatinib
时间窗: Days 1-2, Days 5-6, and Days 9-10
Single-dose pharmacokinetic parameters, such as AUC(0-INF) were derived using noncompartmental methods from plasma dasatinib concentration-time data.
次要结局
- Number of Participants With Clinically Significant Changes in Vital Signs or Electrocardiogram (ECG) Findings(Day -1, Screening, and Days 1, 5, 9 and 10 (at study discharge))
- Time of Maximum Observed Plasma Concentration (Tmax) of Dasatinib(Days 1-2, Days 5-6, and Days 9-10)
- Half-life of Dasatinib(Days 1-2, Days 5-6, and Days 9-10)
- Number of Participants With at Least 1 Adverse Event (AE), With at Least 1 Treatment-related AE, Who Discontinued Due to AEs, and With at Least 1 Serious Adverse Event (SAE)(Continually from enrollment through Day 9 and at study discharge on Day 10)
- Number of Participants With Marked Abnormalities in Results of Clinical Laboratory Tests(Day -1, Screening, and Day 9 of current treatment regimen)