Clinical trial NCT02172105: Multiple Rising Inhalative Doses of BI 1744 CL in Healthy Male Volunteers
Official title: A Double-blind, Randomised, Placebo Controlled (Within a Dose Group) Study to Evaluate Safety, Tolerability and Pharmacokinetics of Multiple Rising Inhalative Doses (5 μg, 10 μg and 20 μg) of BI 1744 CL for 14 Days in Healthy Male Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-06-24
Enrollment: 36
Sex: MALE
Minimum age (years): 20
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Study to evaluate safety, tolerability, and pharmacokinetics of BI 1744 CL in healthy Japanese male volunteers.


Eligibility criteria: Inclusion Criteria:

* Healthy Japanese men: According to the results of a complete medical history, the physical examination, vital signs (blood pressure and pulse rate), 12-lead ECG, clinical laboratory tests
* Age ≥20 and ≤35 years
* Body mass index (BMI) ≥18.5 and ≤25.0 kg/m2
* Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation
* Subjects must be able to inhale medication in a competent manner from the Respimat®inhaler

Exclusion Criteria:

* Any finding of the medical examination (including ,blood pressure and pulse rate and ECG) deviating from normal and of clinical relevance
* Any evidence of a clinically relevant concomitant disease
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
* Surgery of the gastrointestinal tract (except appendectomy)
* 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 drug or its excipients)
* 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 before drug administration or during the trial
* Use of prescription or non-prescription drugs within 10 days before drug administration or during the trial. However, over-the-counter drugs for external application (such as lubricant eye drops for contact lens, insect bite reliever) shall be allowed
* Participation in another trial with an investigational drug within four months before drug administration or during the trial
* Smoker (\>10 cigarettes or \>3 cigars or \>3 pipes/day)
* Inability to refrain from smoking on trial days
* Alcohol abuse (more than 60 g/day: corresponds to ca. 3 large bottles of beer, 3 gous (ca. 540 cc) of Japanese sake, 6 shots of whisky, 6 glasses of wine or 6 glasses of Japanese shochu, distilled alcoholic beverage)
* Drug abuse
* Blood donation (more than 100 mL within four weeks before drug administration or during the trial)
* Excessive physical activities (within one week before administration or during the trial)
* Any laboratory value outside the reference range that is of clinical relevance
* Inability to comply with dietary regimen of trial site
* A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 ms) or long QT syndroms
* A history of additional risk factors for torsades de pointes (TdP) (e.g., heart failure, hypokalemia) or other cardiac arrhythmias
* hyperthyroidism
* Disagree with adequate contraception (the subject should use condoms and his partner should use oral contraception or intrauterine device \[IUD\]) during the study

Primary outcomes:
measure: Number of patients with abnormal findings in physical examination
timeFrame: Baseline, up to 13 days after last drug administration
measure: Number of patients with clinically relevant findings in vital signs (blood pressure, pulse rate)
timeFrame: Baseline, up to 13 days after last drug administration
measure: Number of patients with abnormal findings in 12-lead electrocardiogram (ECG)
timeFrame: Baseline, up to 13 days after last drug administration
measure: Number of patients with clinically significant changes in clinical laboratory tests
timeFrame: Baseline, up to 13 days after last drug administration
measure: Change from baseline in potassium level
timeFrame: Baseline and Day 14
measure: Number of patients with adverse events
timeFrame: 7 weeks
measure: Assessment of tolerability on a 4-point scale
timeFrame: Day 28
Secondary outcomes:
measure: Cmax (maximum measured concentration of the analyte in plasma at different time points)
timeFrame: Up to day 18
measure: tmax (time from dosing to maximum measured concentration of the analyte in plasma at different time points)
timeFrame: Up to day 18
measure: AUC (area under the concentration-time curve of the analyte in plasma at different time points)
timeFrame: Up to day 18
measure: %AUCtz-∞ (the percentage of the AUC 0-infinity that is obtained by extrapolation)
timeFrame: Up to day 18
measure: λz (terminal rate constant in plasma at different time points)
timeFrame: Up to day 18
measure: t1/2 (terminal half-life of the analyte in plasma at different time points)
timeFrame: Up to day 18
measure: MRTih (mean residence time of the analyte in the body after inhalation administration at different time points)
timeFrame: Up to day 18
measure: Aeτ (amount of analyte that is eliminated in urine after administration over a uniform dosing interval τ at different time points)
timeFrame: Up to day 18
measure: feτ (fraction of analyte eliminated in urine after administration over a uniform dosing interval τ at different time points)
timeFrame: Up to day 18
measure: CLR (renal clearance of the analyte at different time points)
timeFrame: Up to day 18
measure: Cmin,ss (minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ)
timeFrame: Up to day 18
measure: Cpre,ss (predose concentration of the analyte in plasma at steady state immediately before administration of the next dose)
timeFrame: Up to day 18
measure: AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ)
timeFrame: Up to day 18
measure: CL/F,ss (apparent clearance of the analyte in the plasma at steady state following extravascular multiple dose administration)
timeFrame: Up to day 18
measure: Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration)
timeFrame: Up to day 18
measure: Accumulation ratio (RA,AUC)
timeFrame: Up to day 18
measure: Accumulation ratio (RA,Cmax)
timeFrame: Up to day 18
Other outcomes:
Locations:
Study officials:
References: