Clinical trial NCT02263976: Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of BEA 2180 BR in Healthy Male Subjects
Official title: 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).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-15
Enrollment: 101
Sex: MALE
Minimum age (years): 30
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Number of subjects with clinically significant changes in vital signs
timeFrame: up to 14 days after last drug administration
measure: Number of subjects with clinically significant changes in laboratory parameters
timeFrame: up to 14 days after last drug administration
measure: Changes from baseline in airway resistance (Raw)
timeFrame: up to 120 hours after drug administration
measure: Changes from baseline in specific airway conductance (sGaw)
timeFrame: up to 120 hours after drug administration
measure: Number of subjects with clinically significant findings in 12-lead ECG (electrocardiogram)
timeFrame: up to 14 days after last drug administration
measure: Number of subjects with adverse events
timeFrame: up to 14 days after last drug administration
measure: Assessment of tolerability by investigator on a 5-point scale
timeFrame: within 14 days after last drug administration
Secondary outcomes:
measure: Changes from baseline in salivary secretion
timeFrame: up to 24 hours after drug administration
measure: Changes from baseline in pupil diameter of each eye
timeFrame: up to 4 hours after drug administration
measure: Maximum measured concentration of the analyte in plasma (Cmax)
timeFrame: up to 240 hours after drug administration
measure: Measured concentration of the analyte in plasma (C) for several time points
timeFrame: up to 24 hours after drug administration
measure: Time from dosing to the maximum concentration of the analyte in plasma (tmax)
timeFrame: up to 240 hours after drug administration
measure: Amount of parent drug that is eliminated in urine (Ae)
timeFrame: up to 312 hours after drug administration
measure: Fraction of administered drug excreted unchanged in urine (fe)
timeFrame: up to 312 hours after drug administration
measure: Area under the concentration-time curve of the analyte in plasma (AUC)
timeFrame: up to 240 hours after drug administration
measure: Renal clearance of the analyte (CLR)
timeFrame: up to 312 hours after drug administration
measure: Terminal rate constant of the analyte in plasma (λZ)
timeFrame: up to 240 hours after drug administration
measure: Terminal half-life of the analyte in plasma (t1/2)
timeFrame: up to 240 hours after drug administration
measure: Mean residence time of the analyte in the body after inhaled administration (MRTinh)
timeFrame: up to 240 hours after drug administration
measure: Apparent clearance of the analyte in plasma following extravascular administration (CL/F)
timeFrame: up to 240 hours after drug administration
measure: Apparent volume of distribution during the terminal phase λz following an extravascular dose (VZ/F)
timeFrame: up to 240 hours after drug administration
Other outcomes:
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