Pharmacokinetics, Safety and Tolerability of Single Dose of BI 1744 CL (30 μg Administered With the Respimat® Inhaler) in Patients With Severe Renal Impairment in Comparison to Subjects With Normal Renal Function in a Monocentric, Open Label, Parallel Group Phase I Trial

Boehringer Ingelheim0 sites22 target enrollmentAugust 2009

ConditionsHealthy

InterventionsBI 1774 CL

DrugsBI 1774 CL

Overview

Phase: Phase 1
Intervention: BI 1774 CL
Conditions: Healthy
Sponsor: Boehringer Ingelheim
Enrollment: 22
Primary Endpoint: AUC0-4 (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 4 hours after dosing)
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief Summary

Study to assess the influence of severe renal impairment on the pharmacokinetics (PK), safety, and selected pharmacodynamic (PD) parameters of BI 1744 CL (30 μg administered by inhalation with the Respimat® Inhaler)

Registry

clinicaltrials.gov

Start Date

August 2009

End Date

December 2009

Last Updated

11 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Boehringer Ingelheim

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Healthy subjects:
•Healthy male and female subjects determined by results of screening with a creatinine clearance \>80 mL/min (Treatment Group 2)
•Age 21 - 75 years
•Body Mass Index (BMI) \>=18.5 and \<=32 kg/m2
•Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation
•Renally impaired subjects:
•Renally impaired male or female subjects (Treatment Group 1) determined by results of screening with the following creatinine clearance as estimated according to Cockroft-Gault: Creatinine clearance \<30 mL/min (Treatment Group 1, Renal Function Group 4)
•Age 21 - 75 years
•BMI \>=18.5 and \<=34 kg/m2
•Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation

Exclusion Criteria

•Healthy subjects who meet any of the following criteria will not be entered into this trial:
•Any finding of the medical examination (including blood pressure (BP) \[\>140 mmHg systolic and or \>95 mmHg diastolic\], pulse rate (PR) and electrocardiogram (ECG)) deviating from normal and of clinical relevance
•Any evidence of a clinically relevant concomitant disease
•Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
•Relevant gastrointestinal tract surgery (except appendectomy, herniotomy)
•Diseases of the central nervous system (such as epilepsy, seizures) or psychiatric disorders or neurological disorders
•History of relevant orthostatic hypotension, fainting spells or blackouts
•Chronic or relevant acute infections (e.g. including Hepatitis B and C and HIV)
•History of allergy/hypersensitivity (including drug allergies) that are deemed relevant to the trial as judged by the investigator
•Intake of drugs with a long half-life (\>24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial

Arms & Interventions

severely renally impaired patients

Intervention: BI 1774 CL

healthy volunteers

Intervention: BI 1774 CL

Outcomes

Primary Outcomes

AUC0-4 (area under the concentration time curve of the analyte in plasma over the time interval from 0 to 4 hours after dosing)

Time Frame: before and at 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00 hours following drug administration

Cmax (maximum concentration of the analyte in plasma)

Time Frame: before and at 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00 hours following drug administration

Secondary Outcomes

tmax (time from dosing to the maximum concentration of the analyte in plasma)(before and at 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00 hours following drug administration)
AUC (area under the concentration-time curve of the analyte in plasma at different time points)(before and at 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00 hours following drug administration)
%AUCtz-∞ (percentage of area under the concentration-time curve obtained by extrapolation)(before and at 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00 hours following drug administration)
λz (terminal rate constant in plasma)(before and at 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00 hours following drug administration)
t1/2 (terminal half-life of the analyte in plasma)(before and at 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00 hours following drug administration)
MRTih (mean residence time of the analyte in the body after inhalation)(before and at 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00 hours following drug administration)
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)(before and at 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00 hours following drug administration)
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)(before and at 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00 hours following drug administration)
Aet1-t2 (amount of analyte that is eliminated in urine from the time point t1 to t2)(before and at 0-8, 8-12, 12-24, 24-48, 48-72 hours following drug administration)
fet1-t2 (fraction of analyte excreted in urine from the time point t1 to t2)(before and at 0-8, 8-12, 12-24, 24-48, 48-72 hours following drug administration)
CLR,t1-t2 (renal clearance of the analyte in plasma from the time point t1 to t2)(before and at 0-8, 8-12, 12-24, 24-48, 48-72 hours following drug administration)
Plasma protein binding of BI 1744 BS(before and at 0:05, 0:10, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00, 48:00, 72:00 hours following drug administration)
Number of patients with adverse events(up to 5 weeks)
Assessment of tolerability on a 4-point scale by the investigator(within 5 to 14 days after drug administration)