Safety, Tolerability, and Pharmacokinetics of Single Rising Oral Dose and Multiple Rising Oral Doses of BI 706321 in Healthy Japanese Male Subjects and Single Oral Dose of BI 706321 in Healthy Chinese Male Subjects (Double-blind, Randomised, Placebo-controlled, Parallel Group Design)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Drug-related Adverse Events
研究概览
简要总结
Part I: The main objectives of this trial are to investigate safety, tolerability, and pharmacokinetics (PK) of BI 706321 in healthy Japanese male subjects following oral administration of multiple rising doses.
Part II: The main objectives of this trial are to investigate safety, tolerability, and pharmacokinetics (PK) of BI 706321 in healthy Chinese male subjects following oral administration of single dose.
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
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 20 Years 至 45 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 否
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) including body temperature, 12-lead electrocardiogram (ECG), and clinical laboratory tests at screening visit
- •Part I: Japanese ethnicity, according to the following criteria:
- •-- born in Japan, have lived outside of Japan <10 years
- •Part II: Chinese ethnicity including Taiwanese, according to the following criteria:
- •-- have parents and grandparents who are Chinese
- •Age of 20 to 45 years (inclusive) at screening visit
- •Body mass index (BMI) of 18.5 to 25.0kg/m2 (inclusive) at screening visit
- •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 methods throughout the trial and until three months after the last administration of trial medication. Adequate methods are:
- •A vasectomy performed at least 1 year prior to screening and with medical assessment of the surgical success or
- •Surgical sterilization, 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), or hormonal contraception, such as implants and injectables, combined with oral or vaginal contraceptives, that started at least 2 months prior to first drug administration, or barrier method, e.g., diaphragm with spermicide
排除标准
- •Any finding in the medical examination (including BP, PR, body temperature or ECG) deviating from normal and assessed as clinically relevant by the investigator at screening visit
- •Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 40 to 90 mmHg, or pulse rate outside the range of 40 to 99 bpm at screening visit
- •Any laboratory value outside the reference range that the investigator considers to be of clinical relevance at screening visit
- •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, per investigator judgement
- •History of relevant orthostatic hypotension, fainting spells, or blackouts
- •Further exclusion criteria apply
研究组 & 干预措施
Placebo Matching BI 706321 (Part I)
This trial consisted of two parts: a single-dose part and a multiple-dose part.
Single-Dose Part:
On Day 1, after fasting for at least 10 hours overnight, participants received a single dose of placebo tablets matching BI 706321.
Multiple-Dose Part:
From Day 6 to Day 19, after fasting for at least 10 hours overnight, participants received a daily dose of placebo tablets matching BI 706321.
干预措施: Placebo (Drug)
2 mg BI 706321 (Part I)
This trial consisted of two parts: a single-dose part and a multiple-dose part.
Single-Dose Part:
On Day 1, after fasting for at least 10 hours overnight, participants received a single dose of one 2 milligrams (mg) tablet BI 706321.
Multiple-Dose Part:
From Day 6 to Day 19, after fasting for at least 10 hours overnight, participants received a daily dose of one 2 mg tablet BI 706321.
干预措施: BI 706321 (Drug)
5 mg BI 706321 (Part I)
This trial consisted of two parts: a single-dose part and a multiple-dose part.
Single-Dose Part:
On Day 1, after fasting for at least 10 hours overnight, participants received a single dose of one 5 mg tablet BI 706321.
Multiple-Dose Part:
From Day 6 to Day 19, after fasting for at least 10 hours overnight, participants received a daily dose of one 5 mg tablet BI 706321.
干预措施: BI 706321 (Drug)
8 mg BI 706321 (Part I)
This trial consisted of two parts: a single-dose part and a multiple-dose part.
Single-Dose Part:
On Day 1, after fasting for at least 10 hours overnight, participants received a single dose of three tablets totaling 8 mg of BI 706321.
Multiple-Dose Part:
From Day 6 to Day 19, after fasting for at least 10 hours overnight, participants received a daily dose of three tablets totaling 8 mg of BI 706321.
干预措施: BI 706321 (Drug)
10 mg BI 706321 (Part I)
This trial consisted of two parts: a single-dose part and a multiple-dose part.
Single-Dose Part:
On Day 1, after fasting for at least 10 hours overnight, participants received a single dose of two tablets totaling 10 mg of BI 706321.
Multiple-Dose Part:
From Day 6 to Day 19, after fasting for at least 10 hours overnight, participants received a daily dose of two tablets totaling 10 mg of BI 706321.
干预措施: BI 706321 (Drug)
结局指标
主要结局
Percentage of Participants With Drug-related Adverse Events
时间窗: From 1st drug administration on Day 1 till Day 19 + 16 days Residual Effect Period (REP), up to 35 days.
The percentage of participants treated with investigational drug who experience such an event. Percentage of participants with treatment-emergent adverse events assessed as drug-related by the investigator are reported. Percentages are calculated using total number of participants per treatment as the denominator.
次要结局
- Single-Dose Part: Area Under the Concentration-time Curve of the BI 706321 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUCR0-∞)(Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days after first BI 706321 administration.)
- Single-Dose Part: Maximum Measured Concentration of BI 706321 in Plasma (Cmax)(Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days after first BI 706321 administration.)
- Single-Dose Part: Time From Dosing to Maximum Measured Concentration of BI 706321 in Plasma(Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days after first BI 706321 administration.)
- Area Under the Concentration-time Curve of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (AUCτ,ss)(Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days, and additional time points up to 26 days after first BI 706321 administration.)
- Maximum Measured Concentration of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmax,ss)(Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days, and additional time points up to 26 days after first BI 706321 administration.)
- Minimum Concentration of BI 706321 in Plasma at Steady State Over a Uniform Dosing Interval τ (Cmin,ss)(Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days, and additional time points up to 26 days after first BI 706321 administration.)
- Accumulation Ratio Based on Cₘₐₓ (Rᴀ,ᴄₘₐₓ,ₛₛ)(Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days, and additional time points up to 26 days after first BI 706321 administration.)
- Accumulation Ratio Based on AUC₀-ₜ (Rᴀ,ᴀᴜᴄ₀-ₜ,ₛₛ)(Within 3 hours prior to administration and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours, and 1.5, 2, 3, and 4 days, and additional time points up to 26 days after first BI 706321 administration.)