Bioequivalence of the BI 1015550 Low Dose Formulation C2 and the BI 1015550 Low Dose Formulation C1 (Phase 3 Formulation) Following Oral Administration in Healthy Subjects (an Open-label, Randomised, Single-dose, Two-way Crossover Trial)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
研究概览
简要总结
The main objective of this trial is to establish the bioequivalence of the BI 1015550 Formulation C2 (Test, T) and the BI 1015550 Formulation C1 (Reference, R) following a single oral dose administration.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female subject 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 50 years (inclusive)
- •Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)
- •Signed and dated written informed consent in accordance with International Council for Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
- •Female subject who meets any of the following criteria for a highly effective contraception from at least 30 days before the first administration of trial medication until 7 days after last administration
- •Highly effective methods of contraception include:
- •Use of oral hormonal contraception that prevents ovulation, plus condom
- •Use of combined (estrogen and progestogen-containing) hormonal contraception that prevents ovulation (intravaginal or transdermal)
- •Use of progestogen-only hormonal contraception that inhibits ovulation (only injectables or implants)
- •Use of intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
- •Sexually abstinent is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
- •Bilateral tubal occlusion
- •- Women not of childbearing potential (WNOCBP) include:
- •Permanently surgically sterilised (including hysterectomy, bilateral oophorectomy and bilateral salpingectomy)
- •Postmenopausal, defined as no menses for 1 year without an alternative medical cause (in questionable cases a blood sample with levels of follicle stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory) WNOCBP are not required to use any methods of contraception. For in vitro fertilization (IVF) and in foreign countries, female subjects should not participate in egg donation and male subjects should not participate in sperm donation from the first study drug administration, for the duration of the study and for at least 7 days after the last study drug administration.
排除标准
- •Any finding in the medical examination (including BP, PR 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 millimetre(s) of mercury (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) at screening
- •Any laboratory value outside the reference range that the investigator considers to be of clinical relevance, in particular, hepatic parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin) or renal parameters (creatinine) exceeding the upper limit of normal (ULN) at screening
- •Any evidence of a concomitant disease assessed as clinically relevant by the investigator
- •Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders assessed as clinically relevant by the investigator
- •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 including but not limited to depression and suicidal behaviour
- •History of relevant orthostatic hypotension, fainting spells, or blackouts Further exclusion criteria apply.
研究组 & 干预措施
BI 1015550 Formulation C1 (Reference, R) then BI 1015550 Formulation C2 (Test, T)
For this two period crossover study arm, participants received treatment in the following order:
Participants received a single oral dose of nerandomilast (BI 1015550), a low dose film coated tablet (formulation C1, titanium dioxide [TiO2]-containing phase III formulation, reference (R)) with 240 mL water after an overnight fast of at least 10 h (period 1).
Participants received a single oral dose of nerandomilast (BI 10105550), a low dose film coated tablet (formulation C2, titanium dioxide [TiO2] free, test (T)) with 240 mL water after an overnight fast of at least 10 h (period 2).
In between the treatment periods, participants went through a washout period of 10 days.
干预措施: BI 1015550 (Drug)
BI 1015550 Formulation C2 (Test, T) then BI 1015550 Formulation C1 (Reference, R)
For this two period crossover study arm, participants received treatment in the following order:
Participants received a single oral dose of nerandomilast (BI 10105550), a low dose film coated tablet (formulation C2, titanium dioxide [TiO2] free, test (T)) with 240 mL water after an overnight fast of at least 10 h (period 1).
Participants received a single oral dose of nerandomilast (BI 1015550), a low dose film coated tablet (formulation C1, titanium dioxide [TiO2]-containing phase III formulation, reference (R)) with 240 mL water after an overnight fast of at least 10 h (period 2).
In between the treatment periods, participants went through a washout period of 10 days.
干预措施: BI 1015550 (Drug)
结局指标
主要结局
Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
时间窗: Within 3 hours (hrs) prior to and at 15minutes (min), 30min, 45min, 1hrs, 1:15hrs, 1:30hrs, 1:45hrs, 2hrs, 2:30hrs, 3hrs, 3:30hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs, 34hrs, 48hrs, 58hrs, 72hrs, 96hrs, 120hrs, and 144hrs after nerandomilast intake.
Area under the concentration-time curve of nerandomilast in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is presented. The statistical model applied was an analysis of variance (ANOVA), with 'subjects within sequence' as a random effect and 'sequence,' 'period,' and 'treatment' as fixed effects.
Maximum Measured Concentration of Nerandomilast in Plasma (Cmax)
时间窗: Within 3 hours (hrs) prior to and at 15minutes (min), 30min, 45min, 1hrs, 1:15hrs, 1:30hrs, 1:45hrs, 2hrs, 2:30hrs, 3hrs, 3:30hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs, 34hrs, 48hrs, 58hrs, 72hrs, 96hrs, 120hrs, and 144hrs after nerandomilast intake.
Maximum measured concentration of nerandomilast in plasma (Cmax) is presented. The statistical model applied was an analysis of variance (ANOVA), with 'subjects within sequence' as a random effect and 'sequence,' 'period,' and 'treatment' as fixed effects.
次要结局
- Area Under the Concentration-time Curve of Nerandomilast in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)(Within 3 hours (hrs) prior to and at 15minutes (min), 30min, 45min, 1hrs, 1:15hrs, 1:30hrs, 1:45hrs, 2hrs, 2:30hrs, 3hrs, 3:30hrs, 4hrs, 6hrs, 8hrs, 12hrs, 24hrs, 34hrs, 48hrs, 58hrs, 72hrs, 96hrs, 120hrs, and 144hrs after nerandomilast intake.)