A Study in Healthy Japanese Men to Test How Different Doses of BI 1323495 Are Tolerated and How Itraconazole Influences the Amount of BI 1323495 in the Blood

Study Overview
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Brief Summary
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The main objective of the single-rising dose (SRD) part and the multiple rising dose (MD) part is to investigate safety, tolerability, pharmacokinetics and pharmacodynamics (for MD part only) following single rising doses and multiple oral doses of BI 1323495 in healthy male Japanese subjects genotyped as poor metabolizers (PM) and extensive metabolizers (EM) of UGT2B17. The main objective of the drug-drug interaction (DDI) part is to investigate the relative bioavailability of a single oral dose of BI 1323495 when given alone (treatment R) or in combination with itraconazole (treatment T) in healthy male subjects genotyped as PM of UGT2B17.

Official Title
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Safety, Tolerability and Pharmacokinetics of Single Rising Oral Doses and Multiple Oral Doses of BI 1323495 Versus Placebo in Healthy Male Japanese Subjects Genotyped as Poor and Extensive Metabolizers of UGT2B17 (Single-blind, Randomised, Placebo-controlled [Within Dose Groups] Trial), Including an Investigation of Drug-drug Interaction With Itraconazole in Healthy Male Subjects Genotyped as Poor Metabolizers of UGT2B17 (an Open-label, Two-period, Fixed Sequence Trial)

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 1323495
* Drug: Placebo
* Drug: Itraconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects according to the assessment of the investigator, as based on a complete medical history, including a medical examination, vital signs (BP, PR), 12- lead ECG, and clinical laboratory tests Japanese ethnicity, according to the following criteria: --born in Japan, have lived outside of Japan <10 years, and have parents and grandparents who are Japanese Age of 20 to 45 years (inclusive) at screening BMI of 18.5 to 25.0 kg/m2 (inclusive) at screening Signed and dated written informed consent prior to admission to the trial, in accordance with Good Clinical Practice (GCP) and local legislation Subjects who agree to minimize the risk of making their partner pregnant by fulfilling any of the following criteria starting from the first administration of trial medication until 90 days after last administration of trial medication Use of adequate contraception, any of the following methods plus condom: intrauterine device, combined oral contraceptives that started at least 2 months prior to the first drug administration. Vasectomized (vasectomy at least 1 year prior to enrolment) Surgical sterilization (including bilateral tubal occlusion, hysterectomy or bilateral oophorectomy) of the subject's female partner Subjects genotyped as UGT2B17 poor metabolizers, i.e. carrying allele of UGT2B17 gene (*2/*2) (DDI part only) Exclusion Criteria: Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 40 to 90 mmHg, or pulse rate outside the range of 40 to 99 bpm Any laboratory value outside the reference range that the investigator considers to be of clinical relevance Any evidence of a concomitant disease assessed as clinically relevant by the investigator Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair) Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders History of relevant orthostatic hypotension, fainting spells, or blackouts Further exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 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: Sequential Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SRD part, active drug, poor metabolizers<br> | Drug: BI 1323495<br>* BI 1323495<br>|
| Experimental: SRD part, active drug, extensive metabolizers<br> | Drug: BI 1323495<br>* BI 1323495<br>|
| Placebo Comparator: SRD and MD part, placebo<br> | Drug: Placebo<br>* Placebo<br>|
| Experimental: DDI part, poor metabolizers<br>DDI part will be initiated after SRD part | Drug: BI 1323495<br>* BI 1323495<br>Drug: Itraconazole<br>* Itraconazole<br>|
| Experimental: MD part, active drug, poor metabolizers<br> | Drug: BI 1323495<br>* BI 1323495<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with drug-related adverse events (SRD and MD part) |  | Up to Day 15 | 
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) (DDI part) |  | Up to Day 8 | 
| Maximum measured concentration of the analyte in plasma (Cmax) (DDI part) |  | Up to Day 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) (SRD part) |  | Up to Day 8 | 
| Maximum measured concentration of the analyte in plasma (Cmax) (SRD part) |  | Up to Day 8 | 
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) (DDI part) |  | Up to Day 8 | 
| Area under the concentration-time curve of the analyte in plasma over a uniform dosing interval of 12 h after administration of the first dose (AUC0-12) (MD part) | After the first dose of BI 1323495 | Up to Day 8 | 
| Maximum measured concentration of the analyte in plasma after the first dose (Cmax) (MD part) | After the first dose of BI 1323495 | Up to Day 8 | 
| Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ (AUCτ,ss) (MD part) | After the last dose of BI 1323495 | Up to Day 8 | 
| Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmax,ss) (MD part) | After the last dose of BI 1323495 | Up to Day 8 |