Safety, Tolerability and Pharmacokinetics Study of BI 1744 CL in Healthy Male Subjects

Safety, Tolerability and Pharmacokinetics of Single Rising Doses of 0.5 μg, 2.5 μg, 5 μg, 10 μg, 15 μg, 20 μg, 25 μg and 30 μg BI 1744 CL (Calculated as Free Base) Given as Intravenous Infusion Over 30 Minutes to Healthy Male Subjects. A Single-centre, Single-blind, Placebo-controlled, Randomised Study.

To investigate safety, tolerability, and pharmacokinetics (PK) of single i.v. doses of BI 1744 CL

Study Overview

• Status: Terminated
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 1744 CL

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male based upon a complete medical history, including the physical examination, regarding vital signs (blood pressure (BP), pulse rate (PR)), 12-lead ECG measurement, and clinical laboratory tests. There is no finding deviating from normal and of clinical relevance. There is no evidence of a clinically relevant concomitant disease.
• Age ≥21 and ≤45 years
• BMI ≥18.5 and <30 kg/m2 (Body Mass Index)
• Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation

Exclusion Criteria:

• Any finding of the medical examination (including BP, PR, and ECG measurements) deviating from normal and of clinical relevance
• Evidence of a clinically relevant concomitant disease
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• History of relevant orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of relevant allergy/hypersensitivity (including allergy to the drug or its excipients) as judged clinically relevant by the investigator
• Intake of drugs with a long half-life (>24 hours) within at least 1 month or less than 10 half-lives of the respective drug prior to medication
• Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to medication
• Participation in another trial with an investigational drug within 2 months prior to medication
• Smoker (>10 cigarettes or >3 cigars or >3 pipes/day)
• Inability to refrain from smoking on trial days as judged by the investigator
• Alcohol abuse (more than 40 g alcohol a day)
• Drug abuse
• Blood donation (more than 100 mL blood within 4 weeks prior to medication or during the trial)
• Excessive physical activities within 1 week prior to randomisation or during the trial
• Any laboratory value outside the reference range that is of clinical relevance
• Inability to comply with dietary regimen of the study centre.

The following exclusion criteria are specific for this study due to the known class side effect profile of ß2-mimetics:

• Asthma or history of pulmonary hyperreactivity
• Hyperthyrosis
• Allergic rhinitis in need of treatment
• Clinically relevant cardiac arrhythmia
• Paroxysmal tachycardia (>100 beats per minute)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: BI 1744 CL; Single rising dose of BI 1744 CL as intravenous (i.v.) infusion	Drug: BI 1744 CL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients with abnormal findings in physical examination	Baseline, Day 10 after drug administration
Number of patients with clinically significant changes in vital signs	Baseline and up to day 10 after drug administration
Number of patients with abnormal changes in 12-lead ECG (electrocardiogram) parameters	Baseline and up to day 10 after drug administration
Number of patients with abnormal changes in laboratory parameters	Baseline and up to day 10 after administration
Number of patients with adverse events	Up to day 10
Assessment of tolerability by investigator on a 4-point scale	Day 10 after drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Cmax (maximum measured concentration of the analyte in plasma)	Up to 48 hours after drug administration
AUC (area under the concentration-time curve of the analyte in plasma at different time points)	Up to 48 hours after drug administration
tmax (time from dosing to maximum measured concentration)	Up to 48 hours after drug administration
%AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation)	Up to 48 hours after drug administration
λz (terminal rate constant in plasma)	Up to 48 hours after drug administration
t1/2 (terminal half-life of the analyte in plasma)	Up to 48 hours after drug administration
MRT (mean residence time of the analyte in the body after intravenous administration)	Up to 48 hours after drug administration
CL (total clearance of the analyte in plasma after intravascular administration)	Up to 48 hours after drug administration
V (apparent volume of distribution at different time points following an intravascular dose)	Up to 48 hours after drug administration
Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2)	Up to 96 hours after drug administration
fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2)	Up to 96 hours after drug administration
CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2)	Up to 96 hours after drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): February 1, 2007

Study Registration Dates

• First Submitted: June 20, 2014
• First Submitted That Met QC Criteria: June 20, 2014
• First Posted (Estimate): June 24, 2014

Study Record Updates

• Last Update Posted (Estimate): June 24, 2014
• Last Update Submitted That Met QC Criteria: June 20, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Olodaterol
• Other Study ID Numbers: 1222.7