Pharmacokinetics, Safety and Tolerability of BIIL 284 BS in Patients With Hepatic Impairment in Comparison to Healthy Volunteers

Hepatic Insufficiency Clinical Trial

Official title:

Pharmacokinetics, Safety and Tolerability of Single Dose BIIL 284 BS in Patients With Hepatic Impairment in Comparison to Healthy Subjects (An Open Label, Matched Pair, Two Center Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02265627
• Other study ID #: 543.26
• Status: Completed
• Phase: Phase 1
• First received: October 15, 2014
• Last updated: October 15, 2014
• Start date: March 2000

Study information

• Verified date: October 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

To investigate the pharmacokinetics of a single dose of BIIL 284 BS in patients with hepatic impairment in comparison to healthy subjects

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. primary completion date: September 2000
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 24 Years to 70 Years

Eligibility

Inclusion Criteria:

Healthy Subjects

• Written informed consent signed and dated prior to participation into the study (including medication washout)

• Male of female 24-70 years of age

• All subjects should be within (+- 20 %) of their ideal body weight (Broca-Index)

• Healthy subjects must be able to be comparably matched to a hepatic impaired patient according to age (+- 5 years), weight (+- 30 lbs), gender, and smoking status

• Volunteers will have no evidence of clinically relevant concomitant disease based upon the following: a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, complete blood count (CBC) with differential and platelets, prothrombin time (PT), blood chemistry, hematology and urinalysis

• Female subjects need to be of non-childbearing potential (post-menopausal), tubal ligation or total hysterectomy) and had to provide a negative pregnancy test at the screening visit or subjects is a male

• Tested negative at the screening visit for the following drug screen panel (barbiturates, benzodiazepines, amphetamines, opiates, cocaine, cannabinoids)

Patients with hepatic impairment

• Written informed consent signed and dated prior to participation into the study (including medication washout)

• Male of female 24-70 years of age

• All subjects should be within (+- 20 %) of their ideal body weight (Broca-Index)

• Proven history of cirrhosis confirmed by liver/spleen scan or biopsy (within one year)

• Hepatic impairment: A Child-Pugh classification of Class A, or B

• Volunteers will have no evidence of clinically relevant concomitant disease (other than hepatic impairment) based upon the following: a detailed medical and surgical history, a complete physical examination including vital signs, 12-lead ECG, CBC with differential and platelets, prothrombin time (PT), blood chemistry, hematology and urinalysis

• Tested negative at the screening visit for the following drug screen panel (barbiturates, benzodiazepines, amphetamines, opiates, cocaine, cannabinoids). Unless known drugs were being used for medicinal reasons. For this reason the sponsor and investigator were notified

• Female patients were of non-childbearing potential (post-menopausal), tubal ligation or total hysterectomy) and had to provide a negative pregnancy test at the screening visit

Exclusion Criteria:

Healthy subjects

• Tested positive for Hepatitis B surface antigen, Hepatitis C antibody or HIV antibody

• Have a significant acute or chronic disease, which could have interfered with the objectives of the study

• Small or difficult to locate arm or hand veins that would impair the clinician's ability to draw multiple blood samples or to place a venous catheter

• Likely to need concomitant medication during the study period, which could interfere with the objectives of the study

• Had given a blood donation during the month preceding the study drug administration

• Alcohol consumption > 2 drinks daily (one drink defined as: 12 ounces of beer, 4 ounces of wine or 1.5 ounces of spirits)

• Coffee or tea consumption > 3 cups per day or xanthine containing drinks > 0.5 liter/day

• History of any clinically significant hematological, respiratory, cardiovascular, renal or central nervous system (CNS) disease or other medical condition that is capable of altering the metabolism or elimination of drugs, or of constituting a risk factor when taking the study drug

• History of drug addiction or alcoholism

• Any medical or psychological condition which could relapse during or immediately after the study

• Use of any drug or nutrient which could induce or inhibit hepatic microsomal enzymes within one month of the start of the study or longer based on the elimination half-life of the drug

• Use of experimental new drug one month prior to study drug administration

• Consumed any medicine whatsoever (including over the counter (OTC) drugs) within two weeks of the scheduled administration of the study drug

Patients with Hepatic Impairment

• Positive serology for HIV

• Have a significant acute or chronic disease (except hepatic disease), which is unstable or could interfere with the objectives of the study

• Small or difficult to locate arm or hand veins that would impair the clinician's ability to draw multiple blood samples or to place a venous catheter

• Have hepatocellular carcinoma, extrahepatic biliary obstruction, surgical portal-systemic shunting, acute hepatitis of any origin

• Digestive bleeding within one month of inclusion

• Likely to need concomitant medication during the study period, which could interfere with the objectives of the study

• Had given a blood donation during the month preceding study entry

• Coffee or tea consumption > 3 cups per day or xanthine containing drinks > 0.5 liter/day

• History of any clinically significant hematological, respiratory, cardiovascular, renal or CNS disease or other medical condition (except hepatic impairment) that is capable of altering the metabolism or elimination of drugs, or of constituting a risk factor when taking the study drug

• Any medical or psychological condition which could relapse during or immediately after the study

• Use of any drug or nutrient which could induce or inhibit hepatic microsomal enzymes within one month of the start of the study or longer based on the elimination half-life of the drug

• Use of experimental new drug within the previous month

Study Design

Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatic Insufficiency

Intervention

Drug:
• BIIL 284 BS

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma concentration-time profiles of the analytes at different time points		Up to 84 hours after drug administration	No
Secondary	Maximum measured concentration of BIIL 315 ZW in plasma (Cmax)		Up to 84 hours after drug administration	No
Secondary	Time from dosing to the maximum concentration of BIIL 315 ZW in plasma (tmax)		Up to 84 hours after drug administration	No
Secondary	Area under the concentration-time curve of BIIL 315 ZW in plasma at different time points (AUC)		Up to 84 hours after drug administration	No
Secondary	Terminal half-life of BIIL 315 ZW in plasma (t1/2)		Up to 84 hours after drug administration	No
Secondary	Total mean residence time of BIIL 315 ZW in the body (MRTtot)		Up to 84 hours after drug administration	No
Secondary	Total apparent clearance of BIIL 315 ZW in plasma after oral administration (CLtot/F)		Up to 84 hours after drug administration	No
Secondary	Apparent volume of distribution during the terminal phase ?z following an extravascular dose (Vz/F)		Up to 84 hours after drug administration	No
Secondary	Number of patients with clinically relevant findings in vital signs	blood pressure, pulse rate	Up to 4 days after drug administration	No
Secondary	Changes from baseline in spirometry		Pre-dose and 1 hour after drug administration	No
Secondary	Number of patients with clinically relevant findings in laboratory tests		Up to 4 days after drug administration	No
Secondary	Number of patients with clinically relevant findings in 12-lead ECG		Up to 4 days after drug administration	No
Secondary	Changes from baseline in physical examination		Pre-dose and 4 days after drug administration	No
Secondary	Number of patients with adverse events		Up to 11 days after drug administration	No

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