Safety, Tolerability, and Pharmacokinetics of Single Rising Oral Doses of BI 706321 in Healthy Male Subjects (Single-blind, Randomised, Placebo-controlled, Parallel Group Design)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 73
- 试验地点
- 1
- 主要终点
- Part I: Percentage of Subjects With Drug-related Adverse Events
研究概览
简要总结
The main objectives are:
- Part I: To investigate safety, tolerability, and pharmacokinetics (PK) of BI 706321 in healthy male subjects following oral administration of single rising doses.
- Part II: The relative bioavailability of BI 706321 after administration of tablets and capsules under fasted conditions will be compared with each other and the effect of food on the tablet bioavailability will be investigated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
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 (BP, PR, oral body temperature), 12-lead ECG, and clinical laboratory tests
- •Age of 18 to 45 years (inclusive) in Part I and of 18 to 55 years (inclusive) in Part II
- •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 GCP and local legislation
排除标准
- •Any finding in the medical examination (including Blood Pressure (BP), (PR), oral body temperature or 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 bpm
- •Any 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 medication or its 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)
- •Intake of an investigational drug in another clinical trial within 60 days of planned administration of investigational drug in the current trial, or concurrent participation in another clinical trial in which investigational drug is administered
- •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 24 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) 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
- •Male subjects with WOCBP partner who are unwilling to use male contraception (condom or sexual abstinence) from time point of administration of trial medication until 30 days thereafter. Sperm donation is not allowed from the time point of drug administration until 30 days thereafter.
- •ALT (alanine transaminase), AST (aspartate transaminase), or creatinine exceed upper limit of normal range at screening, confirmed by a repeat test
- •During COVID-19 pandemic: laboratory test indicative of an ongoing SARS-CoV-2 infection
研究组 & 干预措施
Part I - Placebo oral solution
Part I - Placebo oral solution matching BI 706321 as single dose taken orally with 240 milliliter (mL) of water after an overnight fast of at least 10 hours. Placebo subjects were randomised in a 3:1 ratio over the matching BI 706321 arms.
干预措施: Placebo (Drug)
Part I - 0.3 mg BI 706321 oral solution
Part I - 1.2 mL oral solution of 0.25 mg/mL (0.3 milligram (mg) BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours
干预措施: BI 706321 (Drug)
Part I - 0.6 mg BI 706321 oral solution
Part I - 2.4 mL oral solution of 0.25 mg/mL (0.6 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours.
干预措施: BI 706321 (Drug)
Part I - 1.2 mg BI 706321 oral solution
Part I - 4.8 mL oral solution of 0.25 mg/mL (1.2 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours.
干预措施: BI 706321 (Drug)
Part I - Placebo capsules
Part I - Placebo capsules BI 706321 as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours. Placebo subjects were randomised in a 3:1 ratio over the matching BI 706321 arms.
干预措施: Placebo (Drug)
Part I - 2 mg BI 706321 capsules
Part I - 2 capsules of 1 mg (2 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours.
干预措施: BI 706321 (Drug)
Part I - 4 mg BI 706321 capsules
Part I - 4 capsules of 1 mg (4 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours.
干预措施: BI 706321 (Drug)
Part I - 8 mg BI 706321 capsules
Part I - 8 capsules of 1 mg (8 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours.
干预措施: BI 706321 (Drug)
Part I - 15 mg BI 706321 capsules
Part I - 3 capsules of 5 mg (15 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours.
干预措施: BI 706321 (Drug)
Part I - 25 mg BI 706321 capsules
Part I - 5 capsules of 5 mg (25 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours.
干预措施: BI 706321 (Drug)
Part II - Test 1 (T1), fasted, tablets
Part II - Test 1 (T1), fasted: 2 tablets of 2 mg (4 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours
干预措施: BI 706321 (Drug)
Part II - Test 2 (T2), fed, tablets
Part II - Test 2 (T2), fed: 2 tablets of 2 mg (4 mg BI 706321) as single dose taken orally with 240 mL of water after a high-fat, high-calorie breakfast.
干预措施: BI 706321 (Drug)
Part II - Reference (R), fasted, capsules
Part II - Reference (R), fasted: 4 capsules of 1 mg (4 mg BI 706321) as single dose taken orally with 240 mL of water after an overnight fast of at least 10 hours.
干预措施: BI 706321 (Drug)
结局指标
主要结局
Part I: Percentage of Subjects With Drug-related Adverse Events
时间窗: Between intake of trial medication and the individual subject's end of trial, up to 22 days.
Part I: Percentage of subjects with drug-related adverse events.
Part II: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
时间窗: Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 168 hours after drug administration.
Part II: Area under the concentration-time curve of BI 706321 in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz).
Part II: Maximum Measured Concentration of BI 706321 in Plasma (Cmax)
时间窗: Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 168 hours after drug administration.
Part II: Maximum measured concentration of BI 706321 in plasma (Cmax).
次要结局
- Part I: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)(Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 168 hours after drug administration.)
- Part I: Maximum Measured Concentration of BI 706321 in Plasma (Cmax)(Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 168 hours after drug administration.)
- Part I: Time From Dosing to the Maximum Measured Concentration of BI 706321 in Plasma (Tmax)(Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 168 hours after drug administration.)
- Part II: Area Under the Concentration-time Curve of BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)(Within 3 hours before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 24, 34, 48, 72, 168 hours after drug administration.)