Pharmacokinetics, Safety and Tolerability After Multiple Dose Administration of BI 1467335 in Subjects With Moderate Renal Impairment and Subjects With Normal Renal Function (a Mono-centric, Open-label Study in Matched-group Design)
Overview
- Phase
- Phase 1
- Intervention
- BI 1467335
- Conditions
- Renal Insufficiency
- Sponsor
- Boehringer Ingelheim
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- 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)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Despite of moderate renal impairment (Group 1) healthy male or female subjects according to the assessment of the investigator, 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
- •Estimated glomerular filtration rate (eGFR) based on CKD-EPI formula for Group 1 between 30 and 59 mL/min/1.73m2 and for Group 2 ≥ 90 mL/min/1.73m2
- •Age of 18 to 79 years (incl.)
- •BMI of 18.5 to 34 kg/m2 (incl.)
- •Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and local legislation
- •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.:
- •Use of adequate contraception, e.g. any of the following methods plus condom: implants, injectables, combined oral or vaginal contraceptives (inhibition of ovulation)
- •Hormonal intrauterine device
- •Sexually abstinent (defined as refraining from heterosexual intercourse during the entire period of risk)
- •A vasectomised sexual partner (provided that vasectomy was performed at least 1 year prior to enrolment and the vasectomised partner has received medical assessment of the surgical success)
Exclusion Criteria
- •Healthy subjects
- •Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator
- •Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm
- •Any laboratory value outside the reference range that the investigator considers to be of clinical relevance
- •Any evidence of a concomitant disease judged as clinically relevant by the investigator
- •Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
- •Estimated glomerular filtration rate (eGFR) calculated by CKD-EPI formula \< 90 mL/min/1.73m2
- •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:
- •puts the subjects at risk because of participation in the study
Arms & Interventions
BI 1467335 Normal (R)
Participants with normal renal function.
Intervention: BI 1467335
BI 1467335 Moderate (T)
Participants with moderate renal impairment.
Intervention: BI 1467335
Outcomes
Primary Outcomes
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)
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.
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.
Maximum Measured Concentration of BI 1467335 in Plasma After Administration of the First Dose (Cmax)
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.
Maximum measured concentration of BI 1467335 in plasma after administration of the first dose (Cmax). Standard Error presented is actually geometric Standard Error.
Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Dosing Interval After Administration of the 28th Dose (AUCτ,28)
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 28th dose (AUCτ,28). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".
Maximum Measured Concentration of BI 1467335 in Plasma Following Administration of the 28th Dose (Cmax,28)
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). Standard Error presented is actually geometric Standard Error. As per the protocol, day is counted as "Day 1 = 0:00".
Secondary Outcomes
- Maximum Measured Concentration of BI 1467335 in Plasma Following Administration of the 14th Dose (Cmax,14)(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.)
- Area Under the Concentration-time Curve of BI 1467335 in Plasma Over the Dosing Interval After Administration of the 14th Dose (AUCτ,14)(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.)