Healthy, Renal Insufficiency
Conditions
Brief summary
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.
Interventions
DRUGBI 1015550
BI 1015550
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
Inclusion criteria
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 1015550. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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) | 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) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 R-BI 1015550 (the pharmacologically active R-enantiomer, measured by a chiral assay) in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) 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 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 (mixture of R-(pharmacologically active) and S-(pharmacologically inactive) enantiomers, measured by a non-chiral assay) in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) 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. |
Countries
Germany
Participant flow
Recruitment details
This Phase I trial applied a non-randomised, parallel matched-group design and included participants with moderate or severe renal impairment and participants with normal renal function (matched controls to participants with renal impairment). All trial participants received one 18 milligram BI 1015550 tablet, administered in the fasting state.
Pre-assignment details
All participants were screened for eligibility prior to participation in the trial. Participants attended a specialist site which ensured that the participants strictly met all inclusion and none of the exclusion criteria. Participants were not to be entered in the trial if any of the entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| 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). | 8 |
| 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. | 8 |
| 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. | 10 |
| Total | 26 |
Baseline characteristics
| Characteristic | BI 1015550 Severe Renal Impairment | BI 1015550 Moderate Renal Impairment | BI 1015550 Normal Renal Function | Total |
|---|---|---|---|---|
| Age, Continuous | 66.4 Years STANDARD_DEVIATION 12.3 | 65.3 Years STANDARD_DEVIATION 10.3 | 60.7 Years STANDARD_DEVIATION 11.9 | 63.8 Years STANDARD_DEVIATION 11.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 8 Participants | 10 Participants | 26 Participants |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 4 Participants | 11 Participants |
| Sex: Female, Male Male | 4 Participants | 5 Participants | 6 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 4 / 8 | 3 / 8 | 2 / 8 | 3 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
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)
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.
Time frame: 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.
Population: Pharmacokinetic parameter analysis set (PKS): included all participants in the TS who provided at least one PK endpoint that was defined as primary or secondary and that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. A participant was to be included in the PKS, even if he/she contributed only 1 PK parameter value to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 1015550 Severe renal impairment | 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) | 4367.05 hour*nanomole/Liter |
| BI 1015550 Normal renal function matched to severe renal impairment | 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) | 3312.70 hour*nanomole/Liter |
| BI 1015550 Moderate renal impairment | 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) | 3841.47 hour*nanomole/Liter |
| BI 1015550 Normal renal function matched to moderate renal impairment | 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) | 3014.58 hour*nanomole/Liter |
Comparison: Ratio of adjusted geometric means was 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.90% CI: [93.32, 186.22]
Comparison: Ratio of adjusted geometric means was 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.90% CI: [85.92, 188.99]
Primary
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)
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.
Time frame: 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.
Population: Pharmacokinetic parameter analysis set (PKS): included all participants in the treated set (TS) who provided at least one PK endpoint that was defined as primary or secondary and that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. A participant was to be included in the PKS, even if he/she contributed only 1 PK parameter value to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 1015550 Severe renal impairment | 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) | 3347.73 hour*nanomole/Liter |
| BI 1015550 Normal renal function matched to severe renal impairment | 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) | 2590.32 hour*nanomole/Liter |
| BI 1015550 Moderate renal impairment | 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) | 3141.86 hour*nanomole/Liter |
| BI 1015550 Normal renal function matched to moderate renal impairment | 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) | 2285.92 hour*nanomole/Liter |
Comparison: Ratio of adjusted geometric means was 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.90% CI: [91.62, 182.31]
Comparison: Ratio of adjusted geometric means was 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.90% CI: [89.06, 212.12]
Primary
Maximum Measured Concentration of BI 1015550 in Plasma (Cmax)
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.
Time frame: 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.
Population: Pharmacokinetic parameter analysis set (PKS): included all participants in the TS who provided at least one PK endpoint that was defined as primary or secondary and that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. A participant was to be included in the PKS, even if he/she contributed only 1 PK parameter value to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 1015550 Severe renal impairment | Maximum Measured Concentration of BI 1015550 in Plasma (Cmax) | 404.41 nanomole/Liter |
| BI 1015550 Normal renal function matched to severe renal impairment | Maximum Measured Concentration of BI 1015550 in Plasma (Cmax) | 486.36 nanomole/Liter |
| BI 1015550 Moderate renal impairment | Maximum Measured Concentration of BI 1015550 in Plasma (Cmax) | 359.75 nanomole/Liter |
| BI 1015550 Normal renal function matched to moderate renal impairment | Maximum Measured Concentration of BI 1015550 in Plasma (Cmax) | 397.56 nanomole/Liter |
Comparison: Ratio of adjusted geometric means was 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.90% CI: [60.91, 113.51]
Comparison: Ratio of adjusted geometric means was 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.90% CI: [52.4, 156.26]
Primary
Maximum Measured Concentration of R-BI 1015550 in Plasma (Cmax)
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.
Time frame: 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.
Population: Pharmacokinetic parameter analysis set (PKS): included all participants in the TS who provided at least one PK endpoint that was defined as primary or secondary and that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. A participant was to be included in the PKS, even if he/she contributed only 1 PK parameter value to the statistical assessment.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 1015550 Severe renal impairment | Maximum Measured Concentration of R-BI 1015550 in Plasma (Cmax) | 399.46 nanomole/Liter |
| BI 1015550 Normal renal function matched to severe renal impairment | Maximum Measured Concentration of R-BI 1015550 in Plasma (Cmax) | 464.19 nanomole/Liter |
| BI 1015550 Moderate renal impairment | Maximum Measured Concentration of R-BI 1015550 in Plasma (Cmax) | 367.36 nanomole/Liter |
| BI 1015550 Normal renal function matched to moderate renal impairment | Maximum Measured Concentration of R-BI 1015550 in Plasma (Cmax) | 380.43 nanomole/Liter |
Comparison: Ratio of adjusted geometric means was 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.90% CI: [64.88, 114.15]
Comparison: Ratio of adjusted geometric means was 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.90% CI: [56.8, 164.16]
Secondary
Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
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 extrapolated to infinity (AUC0-∞) 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.
Time frame: 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.
Population: Pharmacokinetic parameter analysis set (PKS): included all participants in the TS who provided at least one PK endpoint that was defined as primary or secondary and that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. A participant was to be included in the PKS, even if he/she contributed only 1 PK parameter value to the statistical assessment. Only participants with available PK data are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 1015550 Severe renal impairment | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 4280.84 hour*nanomole/Liter |
| BI 1015550 Normal renal function matched to severe renal impairment | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3423.14 hour*nanomole/Liter |
| BI 1015550 Moderate renal impairment | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3941.06 hour*nanomole/Liter |
| BI 1015550 Normal renal function matched to moderate renal impairment | Area Under the Concentration-time Curve of BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3112.82 hour*nanomole/Liter |
Comparison: Ratio of adjusted geometric means was 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.90% CI: [85.27, 183.4]
Comparison: Ratio of adjusted geometric means was 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.90% CI: [85.3, 187.92]
Secondary
Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
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 extrapolated to infinity (AUC0-∞) 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.
Time frame: 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.
Population: Pharmacokinetic parameter analysis set (PKS): included all participants in the TS who provided at least one PK endpoint that was defined as primary or secondary and that was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. A participant was to be included in the PKS, even if he/she contributed only 1 PK parameter value to the statistical assessment. Only participants with available PK data are included in the analysis.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| BI 1015550 Severe renal impairment | Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3391.98 hour*nanomole/Liter |
| BI 1015550 Normal renal function matched to severe renal impairment | Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2638.63 hour*nanomole/Liter |
| BI 1015550 Moderate renal impairment | Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 3177.31 hour*nanomole/Liter |
| BI 1015550 Normal renal function matched to moderate renal impairment | Area Under the Concentration-time Curve of R-BI 1015550 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞) | 2333.59 hour*nanomole/Liter |
Comparison: Ratio of adjusted geometric means was 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.90% CI: [87.42, 189.02]
Comparison: Ratio of adjusted geometric means was 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.90% CI: [88.41, 209.69]