BI 1744 CL in Patients With Severe Renal Impairment in Comparison to Subjects With Normal Renal Function

Boehringer Ingelheim

Status and phase

Completed

Phase 1

Conditions

Healthy

Treatments

Drug: BI 1774 CL

Study type

Interventional

Funder types

Industry

Identifiers

NCT02172118

1222.35

Details and patient eligibility

About

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)

Enrollment

22 patients

Sex

All

Ages

21 to 75 years old

Volunteers

Accepts Healthy Volunteers

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
Participation in another trial with an investigational drug within one month after previous single dose administration or two months after previous multiple dose administration prior to administration or during the trial
Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
Inability to refrain from smoking when confined to the study site on trial days
Alcohol abuse (more than 40 g/day in males, more than 20 g/day in females)
Drug abuse, in the investigator's judgement upon review of the patient's history and urine screening for abused substances
Veins unsuited for iv puncture on either arm (e.g. veins which are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture)
Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
Excessive physical activities (within 48 hours prior to trial or during the trial)
Any laboratory value outside the reference range that is of clinical relevance
Inability to comply with dietary regimen of study centre
Subjects not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions

Renally impaired subjects who meet any of the following criteria will not be entered into this trial:

Moderate and severe concurrent liver function impairment (e.g. due to hepatorenal syndrome)
Patients with significant diseases other than renal impairment will be excluded. A significant disease is defined as a disease which in the opinion of the investigator
- put the patient at risk because of participation in the study
- may influence the results of the study
- may influence the patient's ability to participate in the study
- is not in a stable condition
  - Diabetic or hypertensive patients can be entered in this trial if the disease is not significant according to these criteria.
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, excluded are those drugs, the patient is currently taking for treatment of the renal or concomitant disease
Subjects with a change of their chronic medication less than 4 weeks prior to dosing
Participation in another trial with an investigational drug within one month after previous single dose administration or two months after previous multiple dose administration prior to administration or during the trial
Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)
Inability to refrain from smoking when confined to the study site on trial days
Alcohol abuse (more than 40 g/day in males, more than 20 g/day in females)
Drug abuse, in the investigator's judgement upon review of the patient's history and urine screening for abused substances
Veins unsuited for iv puncture on either arm (e.g. veins which are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture)
Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
Excessive physical activities (within 48 hours prior to trial or during the trial)
Clinically relevant laboratory abnormalities (except for renal function tests or deviations of clinical laboratory values that are related to renal impairment)
Hemoglobin < 8 g/dL indicating severe renal anemia (use of erythropoetin is allowed to maintain hematocrit)
Inability to comply with dietary regimen of study centre
Subjects not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions
Systolic blood pressure < 100 or > 180 mm Hg, diastolic blood pressure < 60 or > 110 mm Hg, pulse rate < 50 or > 100 1/min

Exclusion criteria specific for this study due to the known class side effect profile of ß2- mimetics (healthy or renally impaired subjects):

Asthma or history of pulmonary hyperreactivity
Hyperthyrosis
Allergic rhinitis in need of treatment
Clinically relevant cardiac arrhythmia

For female subjects (healthy or renally impaired):

Pregnancy or planning to become pregnant within 2 months of study completion
Positive pregnancy test
No adequate contraception in women of childbearing potential (adequate contraception: e.g. sterilisation, intrauterine device or oral contraception not containing ethinyl estradiol or ethinyl estradiol with an additional barrier method) for at least 3 months prior to participation in the study
Inability to maintain this adequate contraception during the whole trial period
Lactation period