Clinical trial NCT02221375: Safety, Tolerability and Pharmacokinetics of Multiple Rising Doses of Butylated Hydroxytoluene and BI 54903 XX Via Respimat® Soft MistTM Inhaler B in Healthy Male Volunteers
Official title: Safety, Tolerability and Pharmacokinetics of Multiple Rising Inhalative Doses of Butylated Hydroxytoluene Via Respimat Soft MistTM Inhaler B (Sub-study 1) and Safety, Tolerability and Pharmacokinetics of Multiple Rising Inhalative Doses of BI 54903 XX Via Respimat Soft MistTM Inhaler B as Randomised, Double-blind, Placebo-controlled Phase I Trial in Healthy Male Volunteers (Main Study) and Comparison of Systemic Exposure Following a Single Dose of BI 54903 XX Via Respimat Soft MistTM Inhaler B and of a Single Dose of Ciclesonide Via MDI (Randomised, Open-label, Two-way Crossover Sub-study 2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-08-20
Enrollment: 56
Sex: MALE
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the study was to investigate safety, tolerability and pharmacokinetics of butylated hydroxytoluene (BHT) (sub-study 1) administered via Respimat® Soft MistTM Inhaler B (SMI B); to assess safety, tolerability and pharmacokinetics of multiple rising doses of BI 54903 XX administered via Respimat® SMI B (main study), and to compare systemic exposure of single dose BI 54903 XX administered via Respimat® SMI B (sub-study 2) with single dose Alvesco® (ciclesonide) administered via HFA-134a propellant metered dose inhaler (MDI).


Eligibility criteria: Inclusion Criteria:

* Healthy males based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead Electrocardiogram (ECG) and clinical laboratory tests
* Age \>= 21 and \<= 50 years
* BMI \>= 18.5 and \<= 29.9 kg/m2
* 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) 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 h) 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 that could reasonably influence the results of the trial within 10 days prior to administration or during the trial (based on the knowledge at the time of protocol preparation)
* Participation in another trial with an investigational drug within 2 months prior to administration or during the trial
* Smoker (\>10 cigarettes or \>3 cigars or \>3 pipes per day)
* Inability to refrain from smoking on trial days
* Alcohol abuse (more than 60 g per day)
* Drug abuse
* Blood donation (\>100 mL within 4 weeks prior to administration or during the trial)
* Excessive physical activities (within 1 week prior to administration or during the trial)
* Any laboratory value outside the reference range that is of clinical relevance
* Inability to comply with dietary regimen of the trial site
* Bacterial and viral infections of the lung, including active or latent tuberculosis

Primary outcomes:
measure: Number of patients with adverse events
timeFrame: up to 21 days after last drug administration
measure: Number of patients with clinically significant findings in vitals signs
timeFrame: up to 21 days after last drug administration
measure: Number of patients with clinically significant findings in ECG
timeFrame: up to 21 days after last drug administration
measure: Number of patients with clinically significant findings in laboratory tests
timeFrame: up to 21 days after last drug administration
measure: Investigator assessed tolerability on a 4-point scale
timeFrame: up to 21 days after last drug administration
measure: Change in airway resistance (Raw)
timeFrame: baseline, after 80 hours
Secondary outcomes:
measure: Cmax (maximum measured concentration in plasma)
timeFrame: up to 24 hours after last drug administration
measure: tmax (time from dosing to maximum measured concentration in plasma)
timeFrame: up to 24 hours after last drug administration
measure: AUCτ (area under the concentration-time curve in plasma over a uniform dosing interval τ)
timeFrame: up to 24 hours after last drug administration
measure: AUC0-inf (area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity)
timeFrame: up to 24 hours after last drug administration
measure: AUCt1-t2 (area under the concentration-time curve in plasma over the time interval from time t1 to time t2)
timeFrame: up to 24 hours after last drug administration
measure: AUC0-tz (area under the concentration-time curve in plasma over the time interval from 0 to the last quantifiable concentration at tz)
timeFrame: up to 24 hours after last drug administration
measure: %AUCtz-∞ (the percentage of the AUC 0-∞ that is obtained by extrapolation)
timeFrame: up to 24 hours after last drug administration
measure: λz (terminal rate constant in plasma)
timeFrame: up to 24 hours after last drug administration
measure: t1/2 (terminal half-life in plasma)
timeFrame: up to 24 hours after last drug administration
measure: MRTih (mean residence time in the body after inhalation administration)
timeFrame: up to 24 hours after last drug administration
measure: CL/F (apparent clearance in plasma following inhalation administration)
timeFrame: up to 24 hours after last drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase λz following inhalation administration)
timeFrame: up to 24 hours after last drug administration
measure: Aet1-t2 (amount that is eliminated in urine from the time point t1 to time point t2)
timeFrame: up to 24 hours after last drug administration
measure: fet1-t2 (fraction that is eliminated in urine from time point t1 to time point t2)
timeFrame: up to 24 hours after last drug administration
measure: CLR,t1-t2 (renal clearance from the time point t1 until the time point t2)
timeFrame: up to 24 hours after last drug administration
measure: Accumulation ratio based on Cmax (RA,Cmax)
timeFrame: up to 24 hours after last drug administration
measure: Accumulation ratio based on AUC (RA,AUC)
timeFrame: up to 24 hours after last drug administration
measure: Linearity index (LI)
timeFrame: up to 24 hours after last drug administration
measure: Metabolite-to-parent ratio for Cmax (RCmax,Met)
timeFrame: up to 24 hours after last drug administration
measure: Metabolite-to-parent ratio for AUC (AUCt1-t2,Met)
timeFrame: up to 24 hours after last drug administration
Other outcomes:
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Study officials:
References: