Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of BEA 2180 BR in Healthy Male Subjects

Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Rising Inhaled BEA 2180 BR Doses (2.5 μg to 1600 μg Cation Administered With the Respimat®) in Healthy Male Subjects, Alone and Followed by Methacholine Challenge. A Randomised, Double-blind Within Dose Group, Placebo-controlled Study, With a 36 μg Tiotropium Bromide Single Dose Sub-study (Open, Two-fold Crossover).

Main study: To investigate safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of BEA 2180 BR Sub-study; To investigate whether treatment with 36 μg tiotropium bromide is able to protect of methacholine-induced bronchoconstriction compared to baseline (methacholine challenge at screening).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BEA 2180 BR; Device: Respimat® A 4; Drug: Methacholine Chloride; Drug: Spiriva

• Study Type: Interventional
• Enrollment (Actual): 101
• 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:

• Healthy male volunteers based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory test
• No finding deviating from normal and of clinical relevance
• No evidence of a clinically relevant concomitant disease
• Age ≥ 30 and Age ≤ 55 years
• Body Mass Index (BMI) ≥ 18.5 and BMI < 30 kg/m2
• Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation

Exclusion Criteria:

• 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 allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator (or his deputy)
• 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
• 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
• Participation in another trial with an investigational drug within two months prior to administration or during the trial
• Alcohol abuse (more than 60 g/day)
• Drug abuse
• Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
• Excessive physical activities (within one week prior to administration or during the trial)
• Any laboratory value outside the reference range of clinical relevance

Exclusion criteria specific for this study:

• Bronchial hyperreactivity as demonstrated by a 45% change of SGaw at or below a cumulative methacholine concentration of 10 mg/mL = 1%
• Asthma or bronchial hyperreactivity
• Allergic rhinitis (hay fever)
• Glaucoma
• Urinary tract obstruction
• Epilepsy
• History of cardiovascular disease
• History of peptic ulcer disease
• History of thyroid disease

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Device: Respimat® A 4; Drug: Methacholine Chloride; methacholine challenge test
Experimental: BEA 2180 BR; single rising doses	Drug: BEA 2180 BR; Device: Respimat® A 4; Drug: Methacholine Chloride; methacholine challenge test
Experimental: Sub-Study	Drug: Methacholine Chloride; methacholine challenge test; Drug: Spiriva; Other Names: tiotropium bromide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of subjects with clinically significant changes in vital signs	blood pressure, pulse rate, respiratory rate, oral body temperature	up to 14 days after last drug administration
Number of subjects with clinically significant changes in laboratory parameters		up to 14 days after last drug administration
Changes from baseline in airway resistance (Raw)	assessed by body plethysmography	up to 120 hours after drug administration
Changes from baseline in specific airway conductance (sGaw)	assessed by body plethysmography	up to 120 hours after drug administration
Number of subjects with clinically significant findings in 12-lead ECG (electrocardiogram)		up to 14 days after last drug administration
Number of subjects with adverse events		up to 14 days after last drug administration
Assessment of tolerability by investigator on a 5-point scale		within 14 days after last drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in salivary secretion		up to 24 hours after drug administration
Changes from baseline in pupil diameter of each eye	pupillometry	up to 4 hours after drug administration
Maximum measured concentration of the analyte in plasma (Cmax)		up to 240 hours after drug administration
Measured concentration of the analyte in plasma (C) for several time points		up to 24 hours after drug administration
Time from dosing to the maximum concentration of the analyte in plasma (tmax)		up to 240 hours after drug administration
Amount of parent drug that is eliminated in urine (Ae)		up to 312 hours after drug administration
Fraction of administered drug excreted unchanged in urine (fe)		up to 312 hours after drug administration
Area under the concentration-time curve of the analyte in plasma (AUC)		up to 240 hours after drug administration
Renal clearance of the analyte (CLR)		up to 312 hours after drug administration
Terminal rate constant of the analyte in plasma (λZ)		up to 240 hours after drug administration
Terminal half-life of the analyte in plasma (t1/2)		up to 240 hours after drug administration
Mean residence time of the analyte in the body after inhaled administration (MRTinh)		up to 240 hours after drug administration
Apparent clearance of the analyte in plasma following extravascular administration (CL/F)		up to 240 hours after drug administration
Apparent volume of distribution during the terminal phase λz following an extravascular dose (VZ/F)		up to 240 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: August 1, 2003
• Primary Completion (Actual): June 1, 2004

Study Registration Dates

• First Submitted: October 13, 2014
• First Submitted That Met QC Criteria: October 13, 2014
• First Posted (Estimate): October 15, 2014

Study Record Updates

• Last Update Posted (Estimate): October 15, 2014
• Last Update Submitted That Met QC Criteria: October 13, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Cholinergic Agonists; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Miotics; Parasympathomimetics; Bronchoconstrictor Agents; Muscarinic Agonists; Tiotropium Bromide; Bromides; Methacholine Chloride
• Other Study ID Numbers: 1205.1; 1205.9001 (Other Identifier: Boehringer Ingelheim)