Safety, Tolerability, and Pharmacokinetics of Single (Part 1) and Multiple Rising Oral Doses (Part 2) of BI 1015550 in Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Number of Subjects With Drug-related Adverse Events (AEs)
研究概览
简要总结
Part 1 (SRD (Single-rising dose)):
The primary objective of this trial part is to investigate the safety and tolerability of BI 1015550 in healthy male subjects following oral administration of single rising doses.
Secondary objectives are the exploration of the pharmacokinetics of BI 1015550 after single dosing.
Part 2 (MRD (Multiple-rising dose)):
In Part 2, the primary objective is to investigate the safety and tolerability of BI 1015550 in healthy male subjects following oral administration of multiple rising doses.
Secondary objectives are the exploration of the pharmacokinetics of BI 1015550 after multiple dosing.
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, based on a complete medical history including a physical examination, vital signs, 12-lead Electrocardiogram (ECG), and clinical laboratory tests
- •Age of 18 to 45 years (incl.)
- •Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (incl.)
- •Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation
排除标准
- •Any finding in the medical examination (including vital signs or Electrocardiogram (ECG)) is deviating from normal and judged 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 55 to 90 mmHg, or pulse rate outside the range of 50 to 90 beats per minute (bpm)
- •Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
- •Any evidence of a concomitant disease judged as clinically relevant by the investigator
- •Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- •Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy)
- •Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders, including but not limited to mood disorders and any history of suicidality.
- •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 prior to administration of trial medication if that might reasonably influence the results of the trial (incl. 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 trial days
- •Alcohol abuse (consumption of more than 20 g per day)
- •Drug abuse or positive drug screening
- •Blood donation of more than 100 mL within 30 days prior to administration of trial medication or intended donation during the trial
- •Intention to perform excessive physical activities within one week prior to administration of trial medication or during the trial
- •Inability to comply with dietary regimen of 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 Torsades de Pointes (such as heart failure, hypokalemia, or family history of Long QT Syndrome)
- •Subject is assessed as unsuitable for inclusion by the investigator, for instance, because considered not able to understand and comply with study requirements, or has a condition that would not allow safe participation in the study
- •Male subjects who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until two months after the study completion. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female partner (intra-uterine device with spermicide, hormonal contraceptive since at least two months)
- •In addition, the following trial-specific exclusion criteria apply:
- •Positive or missing fecal occult blood (no retest allowed),
- •Positive testing for fecal calprotectin (retest allowed)
- •Positive testing for hematuria if confirmed by microscopic urine analysis (retest allowed)
- •Any lifetime history of suicidal behavior (i.e. actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behavior)
- •Any suicidal ideation (i.e. type 1-5) on the Columbia Suicidal Severity Rating (C-SSRS) in the past 12 months (i.e.passive/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) (only Part 2)
研究组 & 干预措施
Placebo Single Dose (SD)
Subjects received single dose of placebo tablet matching to BI 1015550 orally with 240 milligram (mL) of water after an overnight fast of at least 10 hours (h) on day 1
干预措施: Placebo Single Dose (SD) (Drug)
Placebo Multiple Dose (MD)
Subjects received placebo tablet matching to BI 1015550 twice daily (bid) starting on Day 3 orally with 240 milligram (mL) of water after a moderate fat meal. Subjects were treated for 14 days and received a single morning dose on Day 1, followed by 11 day treatment and a single morning dose on Day 14
干预措施: Placebo Multiple Dose (MD) (Drug)
BI 1015550 36 milligram (mg) Single Dose (SD)
Subjects received single dose of BI 1015550 36 mg (6 tablets of 6 mg) orally with 240 milligram (mL) of water after an overnight fast of at least 10 hours (h) on day 1
干预措施: BI 1015550 Single Dose (SD) (Drug)
BI 1015550 48 milligram (mg) Single Dose (SD)
Subjects received single dose of BI 1015550 48 mg (8 tablets of 6 mg) orally with 240 milligram (mL) of water after an overnight fast of at least 10 hours (h) on day 1
干预措施: BI 1015550 Single Dose (SD) (Drug)
BI 1015550 6 milligram (mg) twice daily Multiple Dose (MD)
Subjects received BI 1015550 6 mg (1 tablet of 6 mg) twice daily (bid) starting on Day 3 orally with 240 milligram (mL) of water after a moderate fat meal. Subjects were treated for 14 days and received a single morning dose on Day 1, followed by 11 day treatment and a single morning dose on Day 14
干预措施: BI 1015550 Multiple Dose (MD) (Drug)
BI 1015550 12 milligram (mg) twice daily Multiple Dose (MD)
Subjects received BI 1015550 12 mg (2 tablets of 6 mg) twice daily (bid) starting on Day 3 orally with 240 milligram (mL) of water after a moderate fat meal. Subjects were treated for 14 days and received a single morning dose on Day 1, followed by 11 day treatment and a single morning dose on Day 14
干预措施: BI 1015550 Multiple Dose (MD) (Drug)
结局指标
主要结局
Number of Subjects With Drug-related Adverse Events (AEs)
时间窗: For SRD: From the administration of study medication until 7 days, up to day 8. For MRD: From the first administration of study medication until 7 days after the last administration of study medication, i.e. up to 21 days after first drug administration.
Number of subjects with drug-related Adverse Events (AEs).
次要结局
- Part 1 (SRD): Area Under the Concentration-time Curve of the BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)(Pharmacokinetic samples were taken within 2:00 hours before and 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 48:00, 72:00, 96:00, 120:00 hours after drug administration)
- Part 2 (MRD) - After the First Dose : Area Under the Concentration-time Curve of the BI 1015550 in Plasma Over a Uniform Dosing Interval Tau After Administration of the First Dose (AUCτ,1)(Pharmacokinetic samples were taken within 2:00 hours before and 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00 hours after drug administration)
- Part 2 (MRD) - After the First Dose : Maximum Measured Concentration of the BI 1015550 in Plasma (Cmax)(Pharmacokinetic samples were taken within 2:00 hours before and 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 47:55 hours after drug administration)
- Part 2 (MRD) - After the Last Dose: Area Under the Concentration-time Curve of the BI 1015550 in Plasma at Steady State Over a Uniform Dosing Interval Tau (AUCtau,ss)(Pharmacokinetic samples were taken within 5 minutes pre-dose and at hours 311:55, 312:15, 312:30, 312:45, 313:00, 313:15, 313:30, 314:00, 315:00, 316:00, 318:00, 320:00, 324:00)
- Part 2 (MRD) - Accumulation Ratio Based on AUC0-tau (RA,AUC)(Up to 324 hours following first drug administration, Please find the time frame in description section.)
- Part 1 (SRD): Maximum Measured Concentration of the BI 1015550 in Plasma (Cmax)(Pharmacokinetic samples were taken within 2:00 hours before and 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 12:00, 24:00, 34:00, 48:00, 72:00, 96:00, 120:00 hours after drug administration)
- Part 2 (MRD) - After the Last Dose: Maximum Measured Concentration of the BI 1015550 in Plasma at Steady State Over a Uniform Dosing Interval Tau (Cmax,ss)(Pharmacokinetic samples were taken within 5 minutes pre-dose and at hours 312:15, 312:30, 312:45, 313:00, 313:15, 313:30, 314:00, 315:00, 316:00, 318:00, 320:00, 324:00, 336:00, 346:00, 360:00, 384:00, 408:00, 432:00, 456:00, 480:00, 504:00)
- Part 2 (MRD) - Accumulation Ratio Based on Cmax,ss (RA,Cmax)(Up to 504 hours following first drug administration, Please find the time frame in description section.)