A Phase 1 interventional study of BI 1467335 in Renal Insufficiency and Healthy, sponsored by Boehringer Ingelheim. Completed at 1 site in Germany. Open to participants aged 18 Years to 79 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-06-04.
Sponsored by Boehringer Ingelheim · Phase 1, Interventional, and Treatment
The primary objective of the current study is to investigate the influence of moderate renal impairment on the pharmacokinetics of multiple doses in comparison to a matched control group with normal renal function.
Male subjects, or female subjects who meet any of the following criteria (according to the CTFG Recommendations related to contraception and pregnancy testing in clinical trials, methods with a failure rate of less than 1% per year) starting from at least 30 days before the first administration of trial medication and until 30 days after trial completion, e.g.:
Exclusion Criteria:
Healthy subjects
Subjects with moderate renal impairment
Subject with significant diseases other than moderate renal impairment. A significant disease is defined as a disease which in the opinion of the investigator:
For all subjects
Female subjects will not be allowed to participate if any of the following applies:
Male subjects will not be allowed to participate if any of the following applies:
Participants with normal renal function.
Drug: BI 1467335
Participants with moderate renal impairment.
Drug: BI 1467335
28 day treatment period
Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Time Interval From 0 to 24 Hours After Administration of the First Dose (AUC0-24)
Area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to 24 hours after administration of the first dose AUC 0-24. Standard Error presented is actually geometric Standard Error. PKS-stat including participants data for AUC(0-24). The pharmacokinetic (PK) analysis set (PKS) included all subjects in the TS who provided at least one PK parameter that was defined as primary or secondary endpoint and who were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
Time frame: Pharmacokinetic (PK) samples were taken 2.00 hours (h) before dosing and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 23.917 h after dosing on day 1.
Maximum Measured Concentration of BI 1467335 in Plasma After Administration of the First Dose (Cmax)
Maximum measured concentration of BI 1467335 in plasma after administration of the first dose (Cmax). Standard Error presented is actually geometric Standard Error.
Time frame: Pharmacokinetic (PK) samples were taken 2.00 h before dosing and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 23.917 h after dosing on day 1.
Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Dosing Interval After Administration of the 28th Dose (AUCτ,28)
Area under the concentration-time curve of BI 1467335 in plasma over the dosing interval after administration of the 28th dose (AUCτ,28). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".
Time frame: Pharmacokinetic samples were taken 0.0833 h before last dose and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 24.00 h after dosing on day 28.
Maximum Measured Concentration of BI 1467335 in Plasma Following Administration of the 28th Dose (Cmax,28)
Maximum measured concentration of BI 1467335 in plasma following administration of the 28th dose (Cmax,28). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".
Time frame: Pharmacokinetic samples were taken 0.0833 h before last dose and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 24.00 h after dosing on day 28.
Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Dosing Interval After Administration of the 14th Dose (AUCτ,14)
Area under the concentration-time curve of BI 1467335 in plasma over the dosing interval after administration of the 14th dose (AUCτ,14). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".
Time frame: Pharmacokinetic samples were taken 0.0833 h before dosing and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 23.917 h after dosing on day 14.
Maximum Measured Concentration of BI 1467335 in Plasma Following Administration of the 14th Dose (Cmax,14)
Maximum measured concentration of BI 1467335 in plasma following administration of the 14th dose (Cmax,14). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".
Time frame: Pharmacokinetic samples were taken 0.0833 h before dosing and 0.25, 0.50, 0.75, 1.00, 1.50, 2.00, 3.00, 4.00, 6.00, 8.00, 10.00, 12.00 and 23.917 h after dosing on day 14.
This was open-label, multiple-dose and matched-group design. 20 participants entered (ten in each of the two groups). Participants with moderate renal impairment were assigned to the moderate group and individually matched participants with normal renal function were assigned to the normal group.
| Milestone | BI 1467335 Normal (R) | BI 1467335 Moderate (T) |
|---|---|---|
| Started | 10 | 10 |
| Completed | 10 | 10 |
| Not completed | 0 | 0 |
Area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to 24 hours after administration of the first dose AUC 0-24. Standard Error presented is actually geometric Standard Error. PKS-stat including participants data for AUC(0-24). The pharmacokinetic (PK) analysis set (PKS) included all subjects in the TS who provided at least one PK parameter that was defined as primary or secondary endpoint and who were not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
| nanomole*hour/Liter (nmol*h/L) | BI 1467335 Normal (R) | BI 1467335 Moderate (T) |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Time Interval From 0 to 24 Hours After Administration of the First Dose (AUC0-24) | 3.97 ± 1.31 | 7.88 ± 1.31 |
Maximum measured concentration of BI 1467335 in plasma after administration of the first dose (Cmax). Standard Error presented is actually geometric Standard Error.
| nanomole/Liter (nmol/L) | BI 1467335 Normal (R) | BI 1467335 Moderate (T) |
|---|---|---|
| Maximum Measured Concentration of BI 1467335 in Plasma After Administration of the First Dose (Cmax) | 3.03 ± 1.24 | 6.01 ± 1.24 |
Area under the concentration-time curve of BI 1467335 in plasma over the dosing interval after administration of the 28th dose (AUCτ,28). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".
| nanomole*hours/Liter (nmol*h/L) | BI 1467335 Normal (R) | BI 1467335 Moderate (T) |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Dosing Interval After Administration of the 28th Dose (AUCτ,28) | 692.42 ± 1.23 | 1566.88 ± 1.23 |
Maximum measured concentration of BI 1467335 in plasma following administration of the 28th dose (Cmax,28). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".
| nanomole/Liter (nmol/L) | BI 1467335 Normal (R) | BI 1467335 Moderate (T) |
|---|---|---|
| Maximum Measured Concentration of BI 1467335 in Plasma Following Administration of the 28th Dose (Cmax,28) | 100.57 ± 1.13 | 141.20 ± 1.13 |
Area under the concentration-time curve of BI 1467335 in plasma over the dosing interval after administration of the 14th dose (AUCτ,14). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".
| nanomole*hour/Liter (nmol*h/L) | BI 1467335 Normal (R) | BI 1467335 Moderate (T) |
|---|---|---|
| Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Dosing Interval After Administration of the 14th Dose (AUCτ,14) | 321.23 ± 1.34 | 532.06 ± 1.34 |
Maximum measured concentration of BI 1467335 in plasma following administration of the 14th dose (Cmax,14). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".
| nanomole/Liter (nmol/L) | BI 1467335 Normal (R) | BI 1467335 Moderate (T) |
|---|---|---|
| Maximum Measured Concentration of BI 1467335 in Plasma Following Administration of the 14th Dose (Cmax,14) | 73.41 ± 1.16 | 94.28 ± 1.16 |
Collected over From first day of study drug administration until End of trial (EOT), up to 41 days.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| BI 1467335 Normal (R) | 0/10 (0%) | 0/10 (0%) | 2/10 (20%) |
| BI 1467335 Moderate (T) | 0/10 (0%) | 0/10 (0%) | 2/10 (20%) |
| Event | BI 1467335 Normal (R) | BI 1467335 Moderate (T) |
|---|---|---|
| HeadacheNervous system disorders | 1/10 | 2/10 |
| VomitingGastrointestinal disorders | 0/10 | 1/10 |
| Rash pruriticSkin and subcutaneous tissue disorders | 1/10 | 0/10 |
Treated Set (TS): The TS included all subjects who were documented to have taken at least one dose of trial medication. This is the full analysis set population in the sense of International council for harmonisation - efficacy guideline 9: statistical principles for clinical trials (ICH-E9).
| Age, Continuous(Years) | BI 1467335 Normal (R) | BI 1467335 Moderate (T) | Total |
|---|---|---|---|
| Mean | 67.5 ± 9.5 | 68.7 ± 10.9 | 68.1 ± 10.0 |
| Sex: Female, Male(Participants) | BI 1467335 Normal (R) | BI 1467335 Moderate (T) | Total |
|---|---|---|---|
| Female | 4 | 4 | 8 |
| Male | 6 | 6 | 12 |
| Ethnicity (NIH/OMB)(Participants) | BI 1467335 Normal (R) | BI 1467335 Moderate (T) | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 10 | 10 | 20 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | BI 1467335 Normal (R) | BI 1467335 Moderate (T) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 10 | 10 | 20 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
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Boehringer Ingelheim