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

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)

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

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