Drug Drug Interaction Trial With Strong CYP3A4 Inhibitor (Itraconazole) in CYP2C19 Extensive Metabolizers and Poor Metabolizers

Study Overview
=================
Brief Summary
-----------------
The objective of the current study is to evaluate the effect of once daily itraconazole on the pharmacokinetics of BI 409306 in poor (PM) and extensive metabolisers (EM) of CYP2C19.

Official Title
-----------------
Open-label, Randomised, Two-way Crossover Study to Assess the Effect of Once Daily Itraconazole on the Pharmacokinetics of BI 409306 After a Single Oral Dose in Healthy Male Volunteers Genotyped as Poor and Extensive Metabolizers of CYP2C19

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: BI 409306
* Drug: Itraconazole
* Drug: BI 409306


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: - Healthy CYP2C19 genotyped male volunteers according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR, respiratory rate, body temperature), 12-lead ECG, ophthalmologic exam, clinical laboratory tests Korean ethnicity according to the following criteria: be a current Korean passport or national identification card holder, and have parents and grandparents who were all born in Korea Age 20 or older than 20 and 45 or younger than 45 years BMI (Body Mass Index) 18.5 or more than 18.5 and BMI 25 or less than 25 kg/m2 Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation. Exclusion criteria: Any finding of the medical examination (including BP, PR, respiratory rate, body temperature 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, hernia surgery) Diseases of the central nervous system (including but not limited to any kind of seizures, migraine, stroke or psychiatric disorders) within the past 6 month History of relevant orthostatic hypotension, fainting spells or blackouts. Chronic or relevant acute infections History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) Intake of drugs with a long half-life (longer than 24 hours) within at least one month or less than 10 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 or that 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 (more than 10 cigarettes or more than 3 cigars or more than 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (more than 20 g/day) 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 more than 450 ms) A history of additional risk factors for Torsade des Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) Abnormality on color vision test or any other finding on ophthalmologic exam that is clinically deemed to potentially interfere with the safety assessment of this trial Subjects who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until two month after the study completion. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female partner (intra-uterine device with spermicide, hormonal contraceptive since at least two month)

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Reference treatment<br>Single oral dose of BI 409306 | Drug: BI 409306<br>* Oral single dose<br>|
| Experimental: Test treatment<br>Single oral dose of BI 409306 and Administration of Itraconazole | Drug: BI 409306<br>* Oral single dose of BI 409306<br>Drug: Itraconazole<br>* Oral dose, twice daily on Day -3, once daily on Day -2 to Day 2 of Itraconazole<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | up to 72 hours after start of drug administration | 
| Cmax (maximum measured concentration of the analyte in plasma) |  | up to 72 hours after start of drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 plasma concentration) |  | up to 72 hours after start of drug administration | 
| tmax (time from dosing to the maximum concentration of the analyte in plasma) |  | up to 72 hours after start of drug administration | 
| t1/2 (terminal half-life of the analyte in plasma) |  | up to 72 hours after start of drug administration |