Relative Bioavailability of a Single Oral Dose of BI 1358894 When Administered Alone or in Combination With Multiple Oral Doses of Itraconazole in Healthy Male Subjects (an Open-label, Fixed Sequence Study)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity
研究概览
简要总结
The main objective of this trial is to investigate the relative bioavailability of BI 1358894 in plasma when given as oral single dose together with multiple oral doses of itraconazole (Test, T) as compared to when given alone as oral single dose (Reference, R).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 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 according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (Blood pressure (BP), Pulse rate (PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests
- •Age of 18 to 45 years (inclusive)
- •Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)
- •Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation
- •Willingness to comply with contraception requirements. Subjects who are sexually active must use adequate contraception with their female partner throughout the study and until 1 month after the last administration of trial medication. Adequate methods are:
- •Sexual abstinence or
- •A vasectomy performed at least 1 year prior to screening (with medical assessment of the surgical success) or
- •Surgical sterilisation (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy) of the subject's female partner or
- •The use of condoms, if the female partner uses an adequate contraception method in addition, e.g., intrauterine device (IUD), hormonal contraception (e.g. implants, injectables, combined oral or vaginal contraceptives) that started at least 2 months prior to first drug administration, or barrier method (e.g. diaphragm with spermicide) Unprotected sexual intercourse with a female partner is not allowed throughout the study and until 1 month after the last administration of trial medication.
- •Exclusion criteria:
- •Any finding in the medical examination (including Blood pressure (BP), Pulse rate (PR) or Electrocardiogram (ECG)) deviating from normal and assessed as clinically relevant by the investigator
- •Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 beats per minute (bpm)
- •C-reactive protein (CRP)> Upper limit of normal (ULN), Erythrocyte sedimentation rate (ESR)≥15 millimeters/h, liver or kidney parameter above ULN, or any other laboratory value outside the reference range that the investigator considers to be of clinical relevance
- •Any evidence of a concomitant disease assessed as clinically relevant by the investigator
- •Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- •Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
- •Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
- •History of relevant orthostatic hypotension, fainting spells, or blackouts
- •Chronic or relevant acute infections
- •History of relevant allergy or hypersensitivity (including allergy to the trial medications or their excipients)
- •Use of drugs within 30 days of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause QT/QTc interval prolongation)
- •Participation in another trial where an investigational drug has been administered within 60 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigational drug
- •Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
- •Inability to refrain from smoking on specified trial days
- •Alcohol abuse (consumption of more than 30 g per day)
- •Drug abuse or positive drug screening
- •Blood donation of more than 100 mL within 30 days of planned administration of trial medication or intended blood donation during the trial
- •Intention to perform excessive physical activities within one week prior to the administration of trial medication or during the trial
- •Inability to comply with the dietary regimen of the trial site
- •A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms in males) or any other relevant ECG finding at screening
- •A history of additional risk factors for Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome)
- •Subject is assessed as unsuitable for inclusion by the investigator, for instance, because the subject is not considered able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study
- •Any lifetime history of suicidal behaviour (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour)
- •Any suicidal ideation of type 2 to 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) in the past 12 months (i.e. active suicidal thought, active suicidal thought with method, active suicidal thought with intent but without specific plan, or active suicidal thought with plan and intent)
- •Any history of drug-induced liver failure.
- •History of ventricular dysfunction or congestive heart failure.
- •Further exclusion criteria apply
排除标准
- 未提供
研究组 & 干预措施
Total of the 2-treatment, 2-period, fixed-sequence trial
Treatment period 1 (Reference (R)): Oral administration of single dose of 10 milligram (mg) BI 1358894 (2 tablets of 5 mg) with 240 milliliter (mL) of water after an high-fat, high-calorie breakfast on Day 1 of Treatment Period 1.
Treatment period 2 (Test (T)): Oral administration of 200 mg itraconazole (20 mL of 10 mg/mL solution) with 240 mL of water after an overnight fast for at least 10 h once daily for 14 days on Days -3 to 11 combined with a single dose of 10 mg BI 1358894 (2 tablets of 5 mg) on Day 1 of Treatment Period 2, 1.5 hours after administration of itraconazole.
Administrations of BI 1358894 were separated by a washout interval of at least 17 days.
干预措施: BI 1358894 (Drug)
Total of the 2-treatment, 2-period, fixed-sequence trial
Treatment period 1 (Reference (R)): Oral administration of single dose of 10 milligram (mg) BI 1358894 (2 tablets of 5 mg) with 240 milliliter (mL) of water after an high-fat, high-calorie breakfast on Day 1 of Treatment Period 1.
Treatment period 2 (Test (T)): Oral administration of 200 mg itraconazole (20 mL of 10 mg/mL solution) with 240 mL of water after an overnight fast for at least 10 h once daily for 14 days on Days -3 to 11 combined with a single dose of 10 mg BI 1358894 (2 tablets of 5 mg) on Day 1 of Treatment Period 2, 1.5 hours after administration of itraconazole.
Administrations of BI 1358894 were separated by a washout interval of at least 17 days.
干预措施: Itraconazole (Drug)
结局指标
主要结局
Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 Extrapolated to Infinity
时间窗: For each period: within 2.5 hours prior and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168, 192, 216, 240, 312 and 480* hours after administration of BI 1358894. *only in the second period.
Area under the concentration-time curve of BI 1358894 in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞). Data presented come from an analysis of variance (ANOVA) model on the logarithmic scale, this model included effects accounting for 'subject' and 'treatment'. The 'subject' effect was considered as random, whereas the 'treatment' effect was considered as fixed.
Maximum Measured Concentration of BI 1358894 in Plasma
时间窗: For each period: within 2.5 hours prior and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168, 192, 216, 240, 312 and 480* hours after administration of BI 1358894. *only in the second period.
Maximum measured concentration of BI 1358894 in plasma (Cmax). Data presented come from an analysis of variance (ANOVA) model on the logarithmic scale, this model included effects accounting for 'subject' and 'treatment'. The 'subject' effect was considered as random, whereas the 'treatment' effect was considered as fixed.
次要结局
- Area Under the Concentration-time Curve of BI 1358894 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point(For each period: within 2.5 hours prior and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 7, 8, 10, 12, 16, 24, 34, 48, 72, 96, 120, 144, 168, 192, 216, 240, 312 and 480* hours after administration of BI 1358894. *only in the second period.)