Clinical trial NCT02259959: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Inhalative Doses of BI 1744 CL in Fixed Dose Combination With Tiotropium Bromide in Healthy Male Volunteers
Official title: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Inhalative Doses (2 μg/5 μg, 10 μg/5 μg, and 40 μg/10 μg) of BI 1744 CL in Fixed Dose Combination With Tiotropium Bromide for 14 Days in Healthy Male Volunteers (Double-blind, Randomised, Placebo Controlled [at Each Dose Level] Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-09
Enrollment: 36
Sex: MALE
Minimum age (years): 21
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate safety, tolerability, pharmacokinetics and pharmacodynamics of BI 1744 CL and Tiotropium Bromide when given as fixed dose combination


Eligibility criteria: Inclusion Criteria:

* Healthy male based upon a complete medical history, including physical examination, regarding vital signs (BP, 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 (GCP) 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 randomization
* 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 randomisation
* Participation in another trial with an investigational drug within 2 months prior to randomisation
* 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 randomisation 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)

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

* Hypersensitivity to tiotropium and/or related drugs of these classes
* History of narrow-angle glaucoma
* History of prostatic hyperplasia
* History of bladder-neck obstruction

Primary outcomes:
measure: Number of subjects with clinically relevant findings in physical examination
timeFrame: Up to day 32
measure: Number of subjects with clinically relevant findings in vital signs
timeFrame: Up to day 32
measure: Number of subjects with clinically relevant findings in 12-lead ECG
timeFrame: Up to day 32
measure: Number of subjects with clinically relevant findings in laboratory tests
timeFrame: Up to day 32
measure: Number of subjects witch clinically relevant changes in additional safety laboratory test parameters
timeFrame: up to 318 hours after start of treatment
measure: Number of subjects with clinically relevant changes in airway resistance (Raw) measured by body plethysmography
timeFrame: Pre-dose, up to 408 hours after start of treatment
measure: Number of subjects with adverse events
timeFrame: Up to day 32
measure: Global assessment of tolerability by investigator on a 4-point scale
timeFrame: Up to day 32
Secondary outcomes:
measure: Maximum concentration in plasma (Cmax)
timeFrame: up to 504 hours after start of treatment
measure: Time from dosing to maximum concentration in plasma (tmax)
timeFrame: up to 504 hours after start of treatment
measure: Area under the concentration-time curve in plasma (AUC)
timeFrame: up to 504 hours after start of treatment
measure: Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)
timeFrame: up to 504 hours after start of treatment
measure: Percentage of AUC 0-∞ that is obtained by extrapolation (%AUCtz-∞)
timeFrame: up to 504 hours after start of treatment
measure: Terminal rate constant in plasma (λz)
timeFrame: up to 504 hours after start of treatment
measure: Terminal half-life in plasma (t½)
timeFrame: up to 504 hours after start of treatment
measure: Mean residence time in the body after inhalation (MRTih)
timeFrame: up to 504 hours after start of treatment
measure: Apparent clearance after extravascular administration (CL/F)
timeFrame: up to 504 hours after start of treatment
measure: Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F)
timeFrame: up to 504 hours after start of treatment
measure: Amount eliminated in urine from the time point t1 to t2 (Aet1-t2)
timeFrame: up to 336 hours after start of treatment
measure: Fraction excreted in urine from time point t1 to t2 (fet1-t2)
timeFrame: up to 336 hours after start of treatment
measure: Renal clearance from the time point t1 until the time point t2 (CLR,t1-t2)
timeFrame: up to 504 hours after start of treatment
measure: Minimum measured concentration in plasma at steady state over a uniform dosing interval τ (Cmin,ss)
timeFrame: up to 504 hours after start of treatment
measure: Predose concentration of the analytes in plasma at steady state immediately before administration of the next dose (Cpre,ss)
timeFrame: Pre-dose every 24 hours
measure: Time of last measurable concentration in plasma (tz)
timeFrame: up to 504 hours after start of treatment
measure: Linearity index (LI)
timeFrame: up to 504 hours after start of treatment
measure: Accumulation ratio based on Cmax (RA,Cmax)
timeFrame: up to 504 hours after start of treatment
measure: Accumulation ratio based on AUCτ (RA,AUC)
timeFrame: up to 504 hours after start of treatment
Other outcomes:
Locations:
Study officials:
References: