An Open Label, Randomized, Four-way Crossover Study in Healthy Male Subjects to Assess the Relative Bioavailability of Sorafenib Tablet for Oral Suspension Compared to Marketed Tablet and to Investigate the Pharmacokinetics of Sorafenib Tablet for Oral Suspension Including Food Effect and Dose Proportionality
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Bayer
- 入组人数
- 30
- 主要终点
- Area Under the Concentration Versus Time Curve From Zero to Last Data Point Greater Than Lower Limit of Quantitation (LLOQ) of Sorafenib in Plasma (AUC[0-tlast]) After Single Oral Dose
研究概览
简要总结
The primary objective of the study is to
• Investigate the relative bioavailability of sorafenib as 400 mg (4 x 100 mg) tablet for oral suspension formulation in comparison to 400 mg (2 x 200 mg) marketed tablet formulation.
The secondary objectives of this study are to
- Evaluate the dose proportionality in sorafenib pharmacokinetics for sorafenib tablet for oral suspension formulation after administration of 200 mg (2 x 100 mg) and 400 mg (4 x 100 mg) dose of sorafenib in fasted state
- Evaluate the effect of food on the pharmacokinetics of the tablet for oral suspension formulation after administration of a single dose of 400 mg sorafenib (4 x 100mg)
- Evaluate the taste and palatability of sorafenib (both formulations)
- Assess the safety and tolerability of sorafenib tablet for oral suspension in healthy male subjects
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy male subjects between the ages of 18 (inclusive) and 45 years (inclusive) at the first screening visit.
- •Body mass index (BMI) between 18.0 (inclusive) and 32.0 kg / m² (inclusive).
- •Non-smoker or former smoker who has stopped smoking at least 3 months before the first study drug administration
- •Ability to understand and follow study-related instructions
- •Any subject who is a sexually active man and has not been surgically sterilized must consent to use a condom during intercourse and ensure that his female partner practices adequate contraception, or he must be willing to refrain from sexual intercourse from the beginning of the trial until 30 days after last study drug administration.
排除标准
- •Medical and surgical history:
- •Failure of a major organ system or a medical disorder that would impair the subject's ability to complete the study or that would alter the absorption and pharmacokinetics of the study drug
- •Active infections or other medical, psychological or social problems of sufficient severity to limit full compliance with the trial
- •Known severe allergies, non-allergic drug reactions, or multiple drug allergies
- •History of clinically significant metabolic, renal, hepatic, or cardiovascular disease or central nervous system disorder
- •Clinically significant illness within 30 days before first study drug administration.
- •Febrile illness within 1 week before the first study drug administration
- •Known hypersensitivity to study drug
- •Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal
- •Electrocardiogram (ECG), blood pressure, heart rate:
- •Clinically relevant findings in the ECG (e.g. a second- or third-degree AV block, prolongation of the QRS complex over 120 msec or of the QTc-interval over 450 msec)
- •Laboratory examination:
- •Clinically relevant deviations of the screened laboratory parameters from reference ranges (especially for gamma-GT, ALT, AST, or bilirubin)
- •Positive results for hepatitis B virus surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), human immune deficiency virus antibodies (anti-HIV)
研究组 & 干预措施
Treatment A-C-B-D
Subjects received a single oral dose of 400 mg sorafenib marketed tablets (2 * 200 mg) in fasting state (Treatment A) in the first intervention period; followed by a single oral dose of 200 mg sorafenib tablets for oral suspension (2 * 100 mg) in fasting state (Treatment C) in the second intervention period; followed by a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) in fasting state (Treatment B) in the third intervention period; and then a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) after a high-fat, high-calorie breakfast (fed state) (Treatment D) in the fourth intervention period. A washout period of at least 10 days was maintained between sorafenib administrations.
干预措施: Sorafenib (BAY43-9006) Film-coated tablet (Drug)
Treatment A-C-B-D
Subjects received a single oral dose of 400 mg sorafenib marketed tablets (2 * 200 mg) in fasting state (Treatment A) in the first intervention period; followed by a single oral dose of 200 mg sorafenib tablets for oral suspension (2 * 100 mg) in fasting state (Treatment C) in the second intervention period; followed by a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) in fasting state (Treatment B) in the third intervention period; and then a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) after a high-fat, high-calorie breakfast (fed state) (Treatment D) in the fourth intervention period. A washout period of at least 10 days was maintained between sorafenib administrations.
干预措施: Sorafenib (BAY43-9006) Oral suspension (Drug)
Treatment B-A-D-C
Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) in fasting state (Treatment B) in the first intervention period; followed by a single oral dose of 400 mg sorafenib marketed tablets (2 * 200 mg) in fasting state (Treatment A) in the second intervention period; followed by a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) after a high-fat, high-calorie breakfast (fed state) (Treatment D) in the third intervention period; and then a single oral dose of 200 mg sorafenib tablets for oral suspension (2 * 100 mg) in fasting state (Treatment C) in the fourth intervention period. A washout period of at least 10 days was maintained between sorafenib administrations.
干预措施: Sorafenib (BAY43-9006) Film-coated tablet (Drug)
Treatment B-A-D-C
Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) in fasting state (Treatment B) in the first intervention period; followed by a single oral dose of 400 mg sorafenib marketed tablets (2 * 200 mg) in fasting state (Treatment A) in the second intervention period; followed by a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) after a high-fat, high-calorie breakfast (fed state) (Treatment D) in the third intervention period; and then a single oral dose of 200 mg sorafenib tablets for oral suspension (2 * 100 mg) in fasting state (Treatment C) in the fourth intervention period. A washout period of at least 10 days was maintained between sorafenib administrations.
干预措施: Sorafenib (BAY43-9006) Oral suspension (Drug)
Treatment C-D-A-B
Subjects received a single oral dose of 200 mg sorafenib tablets for oral suspension (2 * 100 mg) in fasting state (Treatment C) in the first intervention period; followed by a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) after a high-fat, high-calorie breakfast (fed state) (Treatment D) in the second intervention period; followed by a single oral dose of 400 mg sorafenib marketed tablets (2 * 200 mg) in fasting state (Treatment A) in the third intervention period; and then a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) in fasting state (Treatment B) in the fourth intervention period. A washout period of at least 10 days was maintained between sorafenib administrations.
干预措施: Sorafenib (BAY43-9006) Film-coated tablet (Drug)
Treatment C-D-A-B
Subjects received a single oral dose of 200 mg sorafenib tablets for oral suspension (2 * 100 mg) in fasting state (Treatment C) in the first intervention period; followed by a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) after a high-fat, high-calorie breakfast (fed state) (Treatment D) in the second intervention period; followed by a single oral dose of 400 mg sorafenib marketed tablets (2 * 200 mg) in fasting state (Treatment A) in the third intervention period; and then a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) in fasting state (Treatment B) in the fourth intervention period. A washout period of at least 10 days was maintained between sorafenib administrations.
干预措施: Sorafenib (BAY43-9006) Oral suspension (Drug)
Treatment D-B-C-A
Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) after a high-fat, high-calorie breakfast (fed state) (Treatment D) in the first intervention period; followed by a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) in fasting state (Treatment B) in the second intervention period; followed by a single oral dose of 200 mg sorafenib tablets for oral suspension (2 * 100 mg) in fasting state (Treatment C) in the third intervention period; and then a single oral dose of 400 mg sorafenib marketed tablets (2 * 200 mg) in fasting state (Treatment A) in the fourth intervention period. A washout period of at least 10 days was maintained between sorafenib administrations.
干预措施: Sorafenib (BAY43-9006) Film-coated tablet (Drug)
Treatment D-B-C-A
Subjects received a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) after a high-fat, high-calorie breakfast (fed state) (Treatment D) in the first intervention period; followed by a single oral dose of 400 mg sorafenib tablets for oral suspension (4 * 100 mg) in fasting state (Treatment B) in the second intervention period; followed by a single oral dose of 200 mg sorafenib tablets for oral suspension (2 * 100 mg) in fasting state (Treatment C) in the third intervention period; and then a single oral dose of 400 mg sorafenib marketed tablets (2 * 200 mg) in fasting state (Treatment A) in the fourth intervention period. A washout period of at least 10 days was maintained between sorafenib administrations.
干预措施: Sorafenib (BAY43-9006) Oral suspension (Drug)
结局指标
主要结局
Area Under the Concentration Versus Time Curve From Zero to Last Data Point Greater Than Lower Limit of Quantitation (LLOQ) of Sorafenib in Plasma (AUC[0-tlast]) After Single Oral Dose
时间窗: Pre-dose (0 hour) to 120 hours post-dose
Area under the concentration versus time curve from zero to the last data point greater than LLOQ after single dose of sorafenib were measured. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
Maximum Observed Drug Concentration After Single Dose Administration (Cmax) of Sorafenib in Plasma
时间窗: Pre-dose (0 hour) to 120 hours post-dose
Maximum observed drug concentration after single dose administration of sorafenib in plasma was measured. Geometric mean and percentage geometric coefficient of variation (%CV) were reported.
次要结局
- Maximum Observed Drug Concentration After Single Dose Administration Divided by Dose (Cmax/D) of Sorafenib in Plasma(Pre-dose (0 hour) to 120 hours post-dose)
- Area Under the Concentration Versus Time Curve From Zero to Infinity After Single Dose (AUC) of Sorafenib in Plasma(Pre-dose (0 hour) to 120 hours post-dose)
- Area Under the Concentration Versus Time Curve From Zero to Infinity After Single Dose Divided by Dose (AUC/D) of Sorafenib in Plasma(Pre-dose (0 hour) to 120 hours post-dose)
- Area Under the Concentration Versus Time Curve From Zero to Last Data Point Divided by Dose (AUC[0-tlast]/D) of Sorafenib in Plasma(Pre-dose (0 hour) to 120 hours post-dose)
- Total Body Clearance of Sorafenib Calculated After Extravascular Administration (CL/F)(Pre-dose (0 hour) to 120 hours post-dose)
- Time to Reach Maximum Concentration (tmax) of Sorafenib in Plasma(Pre-dose (0 hour) to 120 hours post-dose)
- Half-life Associated With the Terminal Slope (t1/2) of Sorafenib in Plasma(Pre-dose (0 hour) to 120 hours post-dose)
- Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(From start of study treatment up to 30 days after the last sorafenib dose administration)
- Number of Subjects With Various Acceptance Regarding the Taste and Palatability of the Tablet Formulations(Within 5 to 10 min of each administration of sorafenib)