Relative Bioavailability of a Single-dose Administration of BIBW 2992 and Multiple-dose Administration of Ritonavir in Healthy Volunteers

Study Overview
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Brief Summary
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The objective was to investigate the effect of ritonavir, an inhibitor of P-glycoprotein (P-gp) and cytochrome P450 3A4 (CYP3A4), on the pharmacokinetics of BIBW 2992

Official Title
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Relative Bioavailability of a Single Oral Dose of BIBW 2992 (20 mg) After Coadministration With Multiple Oral Doses of Ritonavir (200 mg Bid for 3 Days) Compared to the Bioavailability of a Single Oral Dose of BIBW 2992 (20 mg) Alone in Healthy Male Volunteers (an Open-label, Randomised, Two-way Crossover, Clinical Phase I Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBW 2992
* Drug: Ritonavir


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), Pulse 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 7. Chronic or relevant acute infections (e.g. HIV) 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 14 days prior to first 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 BIBW 2992. 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBW 2992 + Ritonavir<br> | Drug: BIBW 2992<br> <br> Drug: Ritonavir<br> <br> |
| Active Comparator: BIBW 2992<br> | Drug: BIBW 2992<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to infinity) - BIBW 2992 |  | up to 6 days 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) - BIBW2992 |  | up to 6 days after drug administration | 
| Cmax (maximum measured concentration of the analyte in plasma) - BIBW 2992 |  | up to 6 days after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-24 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 hours) - BIBW 2992 |  | up to 6 days after drug administration | 
| %AUCtz-∞ (percentage of the AUCtz-∞ that is obtained by extrapolation from the last quantifiable data point to infinity) - BIBW 2992 |  | up to 6 days after drug administration | 
| tmax (time from dosing to the maximum concentration of the analyte in plasma) - BIBW 2992 |  | up to 6 days after drug administration | 
| λz (terminal rate constant in plasma) - BIBW 2992 |  | up to 6 days after drug administration | 
| t1/2 (terminal half-life of the analyte in plasma) - BIBW 2992 |  | up to 6 days after drug administration | 
| MRTpo (mean residence time of the analyte in the body after oral administration) - BIBW 2992 |  | up to 6 days after drug administration | 
| CL/F (apparent clearance of the analyte in the plasma after extravascular administration) - BIBW 2992 |  | up to 6 days after drug administration | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) - BIBW 2992 |  | up to 6 days 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 | 
| Number of patients with abnormal changes in 12-lead electrocardiogram (ECG) |  | Screening, up to 20 days after drug administration | 
| Assessment of tolerability by investigator on a 4-point scale |  | up to 20 days after drug administration |