Safety and Tolerability of 4 Different Dosage Strengths of BIBW 2992 Tablets to Healthy Male Volunteers

Study Overview
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Brief Summary
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Study to assess pharmacokinetics incl. dose proportionality, safety and tolerability of 4 different dosage strengths of BIBW 2992 tablets (final formulation of 20 mg, 30 mg, 40 mg, 50 mg) administered as single doses to healthy male volunteers

Official Title
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Pharmacokinetics, Safety and Tolerability of BIBW 2992 Administered Orally as 20 mg, 30 mg, 40 mg, and 50 mg Tablets (Final Formulation) to Healthy Male Volunteers in an Open-label, Single Rising Dose, Phase I Trial

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBW 2992 MA2 - single rising dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males according to a complete medical history, including a physical examination, vital signs (blood pressure, pulse rate), 12-lead Electrocardiogram (ECG), and clinical laboratory tests Age 21 to 55 years, inclusive Body mass index 18.5 to 29.9 kg/m2, inclusive 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 Blood Pressure (BP), Puse Rate (PR) and Electrocardiogram (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 drug allergy or its excipients) Intake of drugs with a long half-life (>24 hours) within 1 month prior to administration of the trial drug or during the trial Use of any drugs (including herbal preparations, vitamins and nutrient supplements) within 10 days prior to administration of the trial drug or during the trial 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/day) Inability to refrain from smoking within the in-house periods from 12 hours before until 25 hours after each administration of the trial drug Alcohol abuse (more than 30 g/day) Drug abuse Blood donation (more than 100 mL within 4 weeks prior to administration of the trial drug or during the trial) Excessive physical activities (within 1 week prior to administration of the trial drug 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) A history of additional risk factors for Torsades de Points, e.g., heart failure, hypokalemia, family history of Long QT Syndrome Exclusion criteria specific for this study: History of clinically relevant skin diseases, psoriasis or moderate/severe acne History or evidence of interstitial lung disease Males who are unwilling to use a medically acceptable method of contraception during the first 3 months after administration of the trial drug. Acceptable methods of contraception for use by male volunteers include sexual abstinence, a vasectomy performed at least 1 year prior to dosing, barrier contraception or another medically accepted contraceptive method

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBW 2992 MA2 - single rising dose<br> | Drug: BIBW 2992 MA2 - single rising dose<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum measured concentration of the analyte in plasma) |  | predose, up to120 h after drug administration | 
| AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point) |  | predose, up to 120 h after drug administration | 
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | predose, up to 120 h after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| %AUCtz-∞ (percentage of the AUCtz-∞ obtained by extrapolation from the last quantifiable data point to infinity) |  | predose, up to 120 h after drug administration | 
| AUC0-24 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 [predose] to 24 h) |  | predose, up to 120 h after drug administration | 
| tmax (time from dosing to the maximum concentration of the analyte in plasma) |  | predose, up to 120 h after drug administration | 
| λz (terminal rate constant of the analyte in plasma) |  | predose, up to 120 h after drug administration | 
| t1/2 (terminal half-life of the analyte in plasma) |  | predose, up to 120 h days after drug administration | 
| MRTpo (mean residence time of the analyte in the body after oral administration) |  | predose, up to 120 h after drug administration | 
| CL/F (apparent clearance of the analyte in plasma after extravascular administration) |  | predose, up to 120 h after drug administration | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) |  | predose, up to 120 h after drug administration | 
| Number of patients with abnormal findings in physical examination |  | Screening, up to 20 days after drug administration | 
| Number of patients with clinically significant changes in vital signs (blood pressure, pulse rate) |  | Screening, up to 20 days after drug administration | 
| Number of patients with abnormal changes in laboratory parameters |  | Screening, up to 20 days after drug administration | 
| Number of patients with adverse events |  | up to 41 days | 
| Assessment of tolerability by investigator on a 4-point scale |  | up to 20 days after drug administration | 
| Number of patients with abnormal changes in 12-lead electrocardiogram (ECG) |  | Screening, up to 20 days after drug administration |