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Bioavailability of BI 1356 After Co-administration With Ritonavir Compared to the Bioavailability of BI 1356 Alone in Healthy Male Volunteers

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT02183441
Lead Sponsor
Boehringer Ingelheim
Brief Summary

Study to investigate the effect of the P-gp and cytochrome P450 (CYP) 3A4 inhibitor ritonavir on the pharmacokinetics of BI 1356

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
12
Inclusion Criteria
  • Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests
  • Age ≥ 18 and Age ≤ 50 years
  • BMI ≥ 18.5 and BMI ≤ 29.9 kg/m2 (Body Mass Index)
  • 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 (e.g. HIV)
  • History of relevant allergy/hypersensitivity (including allergy to drug or its excipients)
  • Intake of drugs with a long half-life (> 24 hours) within at least one month or less than five 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 (especially unspecific inducing agents like St.John´s wort (Hypericum perforatum) or drugs which prolong the QT/QTc interval 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) or inability to stop alcoholic beverages for 24 hours prior to dosing and up to the last sampling time point
  • 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 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:

  • Galactose intolerance
  • Lactase deficiency
  • Glucose-galactose-malabsorption

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
BI 1356BI 1356Treatment B: BI 1356 alone
BI 1356 plus ritonavirBI 1356Treatment A: 3 days of ritonavir, 1 day BI 1356
BI 1356 plus ritonavirRitonavirTreatment A: 3 days of ritonavir, 1 day BI 1356
Primary Outcome Measures
NameTimeMethod
AUC0-24 (Area under the concentration-time curve of BI 1356 in plasma over the time interval from 0 to 24 hours)up to 24 hours after start of treatment
Cmax (Maximum measured concentration of BI 1356 in plasma)up to 96 hours after start of treatment
Secondary Outcome Measures
NameTimeMethod
AUC (Area under the concentration time curve of the analytes in plasma at different time points)up to 96 hours after start of treatment
λz (Terminal rate constant of the analytes in plasma)up to 96 hours after start of treatment
CL/F (Apparent clearance of BI 1356 in plasma after extravascular administration )up to 96 hours after start of treatment
Number of patients with adverse eventsup to 53 days
%AUCtz-∞ (Percentage of the extrapolated part of the area under the concentration time curve of the analytes in plasma from 0 to infinity)up to 96 hours after start of treatment
tmax (Time from dosing to the maximum concentration of the analytes in plasma)up to 96 hours after start of treatment
t1/2 (Terminal half-life of the analytes in plasma)up to 96 hours after start of treatment
Aet1-t2 (Amount of the analytes that is eliminated in urine from the time interval t1 to t2)up to 24 hours after start of treatment
Cmax (Maximum measured concentration of CD 1750 in Plasma)up to 96 hours after start of treatment
MRTpo (Mean residence time in the body after po administration of the analytes in plasma)up to 96 hours after start of treatment
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) of BI 1356up to 96 hours after start of treatment
fet1-t2 (Fraction of BI 1356 excreted unchanged in urine from time point t1 to t2)up to 24 hours after start of treatment
CLR,t1-t2 (Renal clearance of the analytes in plasma)up to 24 hours after start of treatment
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