Clinical trial NCT02183441: Bioavailability of BI 1356 After Co-administration With Ritonavir Compared to the Bioavailability of BI 1356 Alone in Healthy Male Volunteers
Official title: Relative Bioavailability of a Single Oral Dose of BI 1356 (5 mg) After Co-administration With Multiple Oral Doses of Ritonavir (200 mg Bid for 3 Days) Compared to the Bioavailability of a Single Oral Dose of BI 1356 (5 mg) Alone in Healthy Male Volunteers (an Open-label, Randomized, Two-way Crossover, Clinical Phase I Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-07-08
Enrollment: 12
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: AUC0-24 (Area under the concentration-time curve of BI 1356 in plasma over the time interval from 0 to 24 hours)
timeFrame: up to 24 hours after start of treatment
measure: Cmax (Maximum measured concentration of BI 1356 in plasma)
timeFrame: up to 96 hours after start of treatment
Secondary outcomes:
measure: AUC (Area under the concentration time curve of the analytes in plasma at different time points)
timeFrame: up to 96 hours after start of treatment
measure: %AUCtz-∞ (Percentage of the extrapolated part of the area under the concentration time curve of the analytes in plasma from 0 to infinity)
timeFrame: up to 96 hours after start of treatment
measure: tmax (Time from dosing to the maximum concentration of the analytes in plasma)
timeFrame: up to 96 hours after start of treatment
measure: t1/2 (Terminal half-life of the analytes in plasma)
timeFrame: up to 96 hours after start of treatment
measure: λz (Terminal rate constant of the analytes in plasma)
timeFrame: up to 96 hours after start of treatment
measure: MRTpo (Mean residence time in the body after po administration of the analytes in plasma)
timeFrame: up to 96 hours after start of treatment
measure: CL/F (Apparent clearance of BI 1356 in plasma after extravascular administration )
timeFrame: up to 96 hours after start of treatment
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) of BI 1356
timeFrame: up to 96 hours after start of treatment
measure: Aet1-t2 (Amount of the analytes that is eliminated in urine from the time interval t1 to t2)
timeFrame: up to 24 hours after start of treatment
measure: fet1-t2 (Fraction of BI 1356 excreted unchanged in urine from time point t1 to t2)
timeFrame: up to 24 hours after start of treatment
measure: CLR,t1-t2 (Renal clearance of the analytes in plasma)
timeFrame: up to 24 hours after start of treatment
measure: Cmax (Maximum measured concentration of CD 1750 in Plasma)
timeFrame: up to 96 hours after start of treatment
measure: Number of patients with adverse events
timeFrame: up to 53 days
Other outcomes:
Locations:
Study officials:
References: