Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Inhalative Doses of BEA 2180 BR in Healthy Male Volunteers

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Inhalative Doses (20 µg, 50 µg, 100 µg, 200 µg and 400 µg) of BEA 2180 BR for 21 Days in Healthy Male Volunteers (Double-blind, Randomised, Placebo Controlled [at Each Dose Level] Study)

Study to investigate safety and tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of BEA 2180 BR

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BEA 2180 BR; Device: Respimat®

• Study Type: Interventional
• Enrollment (Actual): 59
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy males according to the following criteria (examined at the Screening Visit):

   Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests

   1.1 No finding deviating from normal and of clinical relevance

   1.2 No evidence of a clinically relevant concomitant disease

2. Age ≥30 and ≤55 years
3. BMI ≥18.5 and BMI < 30 kg/m2 (Body Mass Index)
4. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation

Exclusion Criteria:

1. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, or hormonal disorders
2. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
3. History of relevant orthostatic hypotension, fainting spells or blackouts
4. Chronic or relevant acute infections
5. History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the Investigator
6. 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
7. 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 administration or during the trial
8. Participation in another trial with an investigational drug within two months prior to administration or during the trial
9. Smoker (> 10 cigarettes or > 3 cigars or > 3 pipes/day)
10. Inability to refrain from smoking during the trial
11. Alcohol abuse (more than 60 g/day)
12. Drug abuse
13. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
14. Excessive physical activities (within one week prior to administration or during the trial)
15. Any laboratory value outside the reference range if indicative of underlying disease or poor health

Exclusion criteria specific for this study:

• Asthma or chronic obstructive pulmonary disease
• Glaucoma
• Urinary tract obstruction
• Occupational (professional) exposure to antimuscarinic substances

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Device: Respimat®
Experimental: BEA 2180 BR	Drug: BEA 2180 BR; Device: Respimat®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with abnormal findings in physical examination		up to day 42
Number of subjects with clinically significant changes in vital signs		up to day 42
Number of subjects with clinically significant changes in 12-lead electrocardiogram		up to day 42
Number of subjects with clinically significant changes in laboratory parameters		up to day 42
Changes in effective airway resistance (Reff)	Body plethysmography	up to day 25
Changes in specific effective airway conductance (SGeff)	Body plethysmography	up to day 25
Changes in salivary secretion		up to day 21
Number of subjects with adverse events		up to day 42
Assessment of tolerability by the Investigator on a 4-point rating scale		day 42

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum concentration of the analyte in plasma for several time points	up to day 35
Time from dosing to maximum concentration in plasma for several time points	up to day 35
Area under the concentration-time curve of the analyte in plasma for several time points	up to day 35
Amount of analyte that is eliminated in urine for several time points	up to day 34
Fraction of analyte excreted in urine for several time points	up to day 34
Renal clearance of the analyte in plasma for several time points	up to day 34
Minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval	up to day 35
Predose concentration of the analyte in plasma at steady state immediately before administration of the next dose	up to day 35
Terminal rate constant in plasma at steady state (λz,ss)	up to day 35
Terminal half-life of the analyte in plasma at steady state (t1/2,ss)	up to day 35
Mean residence time of the analyte in the body after 21 administrations at steady state (MRTih,ss)	up to day 35
apparent clearance of the analyte in the plasma after extravascular administration at steady state (CL/F,ss)	up to day 35
apparent volume of distribution during the terminal phase λz following an extravascular dose at steady state (Vz/F,ss)	up to day 35
Accumulation ratio (RA) of the analyte in plasma after multiple dose administration over a uniform dosing interval τ	up to day 35
Peak trough fluctuation (PTF)	up to day 35

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 2004
• Primary Completion (Actual): February 1, 2005

Study Registration Dates

• First Submitted: September 30, 2014
• First Submitted That Met QC Criteria: September 30, 2014
• First Posted (Estimate): October 1, 2014

Study Record Updates

• Last Update Posted (Estimate): October 1, 2014
• Last Update Submitted That Met QC Criteria: September 30, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: 1205.2