Pharmacokinetics, Safety and Tolerability of BI 1015550 Following Oral Administration in Male and Female Participants With Different Degrees of Renal Impairment (Severe and Moderate) as Compared With Individually Matched Male and Female Participants With Normal Renal Function (an Open-label, Non-randomised, Single Dose, Parallel, Individual-matched Design Trial)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
研究概览
简要总结
This study is open to adults aged 18 years and older. People without kidney problems and people who have moderate or severe kidney problems can join the study.
The purpose of this study is to find out how a medicine called BI 1015550 is taken up in the blood of people with and without kidney problems. Kidney problems may change how a medicine is taken up in the blood. All participants take a single tablet of BI 1015550.
Participants are in the study for about 2 weeks. During this time, they visit the study site 6 times. On the second visit, participants stay overnight at the study site for 4 nights. At the visits, doctors take blood samples to measure the levels of BI 1015550 in participants' blood. Then they compare the results between the groups of participants with and without kidney problems. The doctors also check participants' health and take note of any unwanted effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria applying to all participants:
- •Male or female participants
- •Age of 18-79 years (inclusive)
- •Body mass index (BMI) of 18.5 to 35.0 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
- •Male participants are not required to use contraception
- •Women of child-bearing potential (WOCBP) are allowed to participate provided they use a highly effective contraception from at least 30 days before the administration of trial medication until 7 days after trial completion.
- •Of note, oral hormonal contraceptives are not considered as highly effective in this study due to the potential CYP3A induction by BI
- •Therefore, the following methods of contraception are considered adequate for female participants of childbearing potential:
- •Use of combined (oestrogen and progestogen containing) hormonal contraception that prevents ovulation (oral, intravaginal or transdermal), plus condom
- •Use of progestogen-only hormonal contraception that inhibits ovulation (only injectables or implants), plus condom
- •Use of intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
- •Sexually abstinent
- •A vasectomised sexual partner who received medical assessment of the surgical success (documented absence of sperm) and provided that partner is the sole sexual partner of the trial participant.
- •Female participants are not considered to be of childbearing potential if they are either surgically sterilised (including hysterectomy) or 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 units per liter (U/L) and oestradiol below 30 nanograms/liter (ng/L) is confirmatory).
- •Further inclusion criteria apply.
排除标准
- •Exclusion criteria applying to all participants:
- •Any evidence of a concomitant disease assessed as clinically relevant by the investigator
- •Cholecystectomy or other surgery of the gastrointestinal (GI) tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
- •Diseases of the central nervous system (CNS) (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders (including but not limited to major depressive disorder)
- •History of relevant orthostatic hypotension, fainting spells, or blackouts
- •Relevant chronic or acute infections
- •Any documented active or suspected malignancy or history of malignancy within 5 years prior to screening, except appropriately treated basal cell carcinoma of the skin or squamous cell carcinoma in situ of the skin or in situ carcinoma of uterine cervix
- •History of relevant allergy or hypersensitivity (including allergy to the trial medication or its excipients)
- •Use of drugs within 30 days (or 5 of their half-lives, whichever is longer) of planned administration of trial medication that might reasonably influence the results of the trial (including drugs that cause QT/QT interval corrected for heart rate (QTc) interval prolongation) Further exclusion criteria apply.
研究组 & 干预措施
BI 1015550 Severe renal impairment
Participants with severe renal impairment (estimated glomerular filtration rate (eGFR)) according to Chronic Kidney Disease Epidemiology Collaboration 15-29 milliliter(mL)/minute(min)/1.73 meter(m)²), and not requiring dialysis, administered orally one film-coated tablet of 18 milligram (mg) of BI 1015550 with 240 mL of water after an overnight fast of at least 10 hours (h).
干预措施: BI 1015550 (Drug)
BI 1015550 Moderate renal impairment
Participants with moderate renal impairment (eGFR 30-59 mL/min/1.73 m²) administered orally one film-coated tablet of 18 mg of BI 1015550 with 240 mL of water after an overnight fast of at least 10 h.
干预措施: BI 1015550 (Drug)
BI 1015550 Normal renal function
Participants with normal renal function (eGFR ≥90 mL/min/1.73 m²) administered orally one film-coated tablet of 18 mg of BI 1015550 with 240 mL of water after an overnight fast of at least 10 h.
Participants with normal renal function were individually matched by age (± 10 years), gender, weight (± 15%), and race to the participants with renal impairment. Each participant with normal renal function could be matched to one participant with moderate renal impairment and to one participant with severe renal impairment.
干预措施: BI 1015550 (Drug)
结局指标
主要结局
Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
时间窗: Within 2 hours (h) prior to drug administration and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 and 144 h after drug administration.
Area under the concentration-time curve of R-BI 1015550 (the pharmacologically active R-enantiomer, measured by a chiral assay) in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'degree of renal impairment' as fixed effect as well as 'matched pair' as random effect. These quantities were then back-transformed to the original scale. The ratio of adjusted geometric means is calculated with patients with renal impairment as test groups and their respective matched controls as reference groups.
Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
时间窗: Within 2 hours (h) prior to drug administration and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 and 144 h after drug administration.
Area under the concentration-time curve of BI 1015550 (mixture of R-(pharmacologically active) and S-(pharmacologically inactive) enantiomers, measured by a non-chiral assay) in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'degree of renal impairment' as fixed effect as well as 'matched pair' as random effect. These quantities were then back-transformed to the original scale. The ratio of adjusted geometric means is calculated with patients with renal impairment as test groups and their respective matched controls as reference groups.
Maximum Measured Concentration of R-BI 1015550 in Plasma (Cmax)
时间窗: Within 2 hours (h) prior to drug administration and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 and 144 h after drug administration.
Maximum measured concentration of R-BI 1015550 (the pharmacologically active R-enantiomer, measured by a chiral assay) in plasma (Cmax) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'degree of renal impairment' as fixed effect as well as 'matched pair' as random effect. These quantities were then back-transformed to the original scale. The ratio of adjusted geometric means is calculated with patients with renal impairment as test groups and their respective matched controls as reference groups.
Maximum Measured Concentration of BI 1015550 in Plasma (Cmax)
时间窗: Within 2 hours (h) prior to drug administration and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 and 144 h after drug administration.
Maximum measured concentration of BI 1015550 (mixture of R-(pharmacologically active) and S-(pharmacologically inactive) enantiomers, measured by a non-chiral assay) in plasma (Cmax) is reported. Geometric least square mean (adjusted geometric mean) and adjusted geometric standard error were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetic (PK) endpoints were log-transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'degree of renal impairment' as fixed effect as well as 'matched pair' as random effect. These quantities were then back-transformed to the original scale. The ratio of adjusted geometric means is calculated with patients with renal impairment as test groups and their respective matched controls as reference groups.
次要结局
- Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)(Within 2 hours (h) prior to drug administration and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 and 144 h after drug administration.)
- Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)(Within 2 hours (h) prior to drug administration and 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120 and 144 h after drug administration.)