Safety, Tolerability and Pharmacokinetics of BIBW 2948 BS in Healthy Male Volunteers

Study Overview
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Brief Summary
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Study to investigate safety, tolerability, and pharmacokinetics of BIBW 2948 BS

Official Title
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A Randomised, Double-blind, Placebo-controlled (Within Dose Groups) Study to Evaluate Safety, Tolerability and Pharmacokinetics of Single Rising Inhaled Doses BIBW 2948 BS (0.75 to 150 mg Inhalation Powder, Hard Capsule for HandiHaler®) in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBW 2948 BS for oral inhalation
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males based on a complete medical history, including physical examination, vital signs (BP, PR), 12-lead ECG, and clinical laboratory tests: No finding deviating from normal and of clinical relevance No evidence of a clinically relevant concomitant disease Aged between ≥21 and ≤50 years BMI (Body Mass Index) between ≥18.5 and ≤30 kg/m2 Provision of written informed consent signed and dated prior to admission to the study in accordance with good clinical practice (GCP) and local legislation Exclusion Criteria: Any finding during 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 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) 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 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) 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 that is of clinical relevance Inability to comply with dietary regimen of study centre

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBW 2948 BS in single rising doses<br> | Drug: BIBW 2948 BS for oral inhalation<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from baseline in vital signs (blood pressure, pulse rate, respiratory rate, orthostasis test, oral body temperature) |  | Up to 8 days after start of treatment | 
| Changes from baseline in clinical laboratory tests |  | Up to 8 days after start of treatment | 
| Changes from baseline in 12-lead electrocardiogram (ECG) |  | Up to 8 days after start of treatment | 
| Number of patients with adverse events |  | Up to day 29 | 
| Changes from baseline in airway resistance (Raw) | measured via plethysmography | Pre-dose, up to 24 hours after start of treatment | 
| Assessment of tolerability by investigator, a 4-point scale |  | Up to 8 days after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of the analytes in plasma at different time points (AUCt1-t2) |  | Pre-dose, up to 48 hours after start of treatment | 
| Maximum concentration of BIBW 3056 ZW in plasma (Cmax) |  | Pre-dose, up to 48 hours after start of treatment | 
| Time from dosing to maximum concentration of the analytes in plasma (tmax) |  | Pre-dose, up to 48 hours after start of treatment | 
| Amount of BIBW 3056 ZW eliminated in urine at different time points (Aet1-t2) |  | Pre-dose, up to 48 hours after start of treatment | 
| Fraction of BIBW 3065 ZW eliminated in urine at different time points (fet1-t2) |  | Pre-dose, up to 48 hours after start of treatment | 
| Renal clearance of BIBW 3056 ZW from 0 to 24 hours (CLR,0-24) |  | Pre-dose, up to 48 hours after start of treatment | 
| Terminal rate constant of BIBW 3056 ZW in plasma (λz) |  | Pre-dose, up to 48 hours after start of treatment | 
| Terminal half life of BIBW 3056 ZW in plasma (t½) |  | Pre-dose, up to 48 hours after start of treatment | 
| Mean residence time of BIBW 3056 ZW in the body after inhalation (MRTih) |  | Pre-dose, up to 48 hours after start of treatment | 
| Apparent clearance of BIBW 3056 ZW in the plasma after extravascular administration (CL/F) |  | Pre-dose, up to 48 hours after start of treatment | 
| Apparent volume of distribution of BIBW 3056 ZW during the terminal phase λz following an extravascular dose (Vz/F) |  | Pre-dose, up to 48 hours after start of treatment | 
| The percentage of the AUC 0-∞ that is obtained by extrapolation (%AUCtz-∞) |  | Pre-dose, up to 48 hours after start of treatment |