Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of BEA 2180 BR in Healthy Male Subjects
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT02263976
- Lead Sponsor
- Boehringer Ingelheim
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 101
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - Sub-Study Spiriva - Placebo Respimat® A 4 - Placebo Methacholine Chloride - BEA 2180 BR BEA 2180 BR single rising doses BEA 2180 BR Respimat® A 4 single rising doses Sub-Study Methacholine Chloride - BEA 2180 BR Methacholine Chloride single rising doses
- Primary Outcome Measures
Name Time Method Number of subjects with adverse events up to 14 days after last drug administration Number of subjects with clinically significant findings in 12-lead ECG (electrocardiogram) 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 Number of subjects with clinically significant changes in vital signs up to 14 days after last drug administration blood pressure, pulse rate, respiratory rate, oral body temperature
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) up to 120 hours after drug administration assessed by body plethysmography
Changes from baseline in specific airway conductance (sGaw) up to 120 hours after drug administration assessed by body plethysmography
- Secondary Outcome Measures
Name Time Method Fraction of administered drug excreted unchanged in urine (fe) up to 312 hours after drug administration Changes from baseline in salivary secretion up to 24 hours after drug administration Changes from baseline in pupil diameter of each eye up to 4 hours after drug administration pupillometry
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 Amount of parent drug that is eliminated in urine (Ae) up to 312 hours after drug administration Terminal half-life of the analyte in plasma (t1/2) up to 240 hours after drug administration Renal clearance of the analyte (CLR) 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 Terminal rate constant of the analyte in plasma (λZ) up to 240 hours after drug administration Time from dosing to the maximum concentration of the analyte in plasma (tmax) 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