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
Phase 1
Completed
- Conditions
- Healthy
- Interventions
- Drug: BI 54903 XX highDrug: BI 54903 XX medium 2Drug: BI 54903 XX lowDrug: BI 54903 XX medium 1
- Registration Number
- NCT02221375
- Lead Sponsor
- Boehringer Ingelheim
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 56
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BHT high BHT high - BI 54903 XX high BI 54903 XX high - BI 54903 XX medium single dose BI 54903 XX medium 2 - BI 54903 XX low BI 54903 XX low - BHT low BHT low - BHT medium BHT medium - Ciclesonide Ciclesonide - BI 54903 XX medium 1 BI 54903 XX medium 1 - BI 54903 XX medium 2 BI 54903 XX medium 2 -
- Primary Outcome Measures
Name Time Method Number of patients with clinically significant findings in ECG up to 21 days after last drug administration Number of patients with adverse events up to 21 days after last drug administration Number of patients with clinically significant findings in vitals signs up to 21 days after last drug administration Number of patients with clinically significant findings in laboratory tests up to 21 days after last drug administration Investigator assessed tolerability on a 4-point scale up to 21 days after last drug administration Change in airway resistance (Raw) baseline, after 80 hours
- Secondary Outcome Measures
Name Time Method Cmax (maximum measured concentration in plasma) up to 24 hours after last drug administration tmax (time from dosing to maximum measured concentration in plasma) up to 24 hours after last drug administration AUC0-inf (area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity) up to 24 hours after last drug administration AUCt1-t2 (area under the concentration-time curve in plasma over the time interval from time t1 to time t2) up to 24 hours after last drug administration AUCτ (area under the concentration-time curve in plasma over a uniform dosing interval τ) up to 24 hours after last drug administration AUC0-tz (area under the concentration-time curve in plasma over the time interval from 0 to the last quantifiable concentration at tz) up to 24 hours after last drug administration %AUCtz-∞ (the percentage of the AUC 0-∞ that is obtained by extrapolation) up to 24 hours after last drug administration λz (terminal rate constant in plasma) up to 24 hours after last drug administration t1/2 (terminal half-life in plasma) up to 24 hours after last drug administration CL/F (apparent clearance in plasma following inhalation administration) up to 24 hours after last drug administration Accumulation ratio based on Cmax (RA,Cmax) up to 24 hours after last drug administration Accumulation ratio based on AUC (RA,AUC) up to 24 hours after last drug administration Linearity index (LI) up to 24 hours after last drug administration MRTih (mean residence time in the body after inhalation administration) up to 24 hours after last drug administration Metabolite-to-parent ratio for Cmax (RCmax,Met) up to 24 hours after last drug administration Vz/F (apparent volume of distribution during the terminal phase λz following inhalation administration) up to 24 hours after last drug administration Aet1-t2 (amount that is eliminated in urine from the time point t1 to time point t2) up to 24 hours after last drug administration fet1-t2 (fraction that is eliminated in urine from time point t1 to time point t2) up to 24 hours after last drug administration CLR,t1-t2 (renal clearance from the time point t1 until the time point t2) up to 24 hours after last drug administration Metabolite-to-parent ratio for AUC (AUCt1-t2,Met) up to 24 hours after last drug administration