Safety, Tolerability, and Pharmacokinetics of Multiple Rising Doses of BI 425809 Tablets for 12 Days to Young and Elderly Healthy Male and Female Volunteers and Comparison of Pharmacokinetics of a Single Oral Dose of BI 425809 (Morning Versus Evening)

Study Overview
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Brief Summary
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The aim of the study is to investigate the safety, tolerability, and pharmacokinetics of multiple rising doses of BI 425809 tablets given orally once daily for 12 days to young and elderly healthy male and female volunteers and to compare single dose pharmacokinetics of BI 425809 given in the morning and in the evening.

Official Title
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Safety, Tolerability, and Pharmacokinetics of Multiple Rising Doses of BI 425809 Tablets Given Orally Once Daily for 12 Days to Young and Elderly Healthy Male and Female Volunteers (Randomised, Double-blind, Placebo-controlled Within Dose Groups Phase I Study)(Part 1) and Comparison of Pharmacokinetics of a Single Oral Dose of BI 425809 After Oral Administration in the Morning Versus Oral Administration in the Evening in Young Healthy Male and Female Volunteers (Randomised, Two-sequence, Open, Two Period, Two-way Cross Over) (Part 2)

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 425809
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy male or female subjects according to the investigator´s assessment, based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR), 12-lead electrocardiogram (ECG), and clinical laboratory tests age of 18 to 50 years (incl.) for young healthy volunteers or age of 65 to 80 years (incl.) for elderly healthy volunteers Body mass index (BMI) of 18.5 to 29.9 kg/m2 (incl.) Signed and dated written informed consent prior to admission to the study in accordance with good clinical practice (GCP) and local legislation Female subjects who meet any of the following criteria: Surgically sterilised Postmenopausal, defined as at least 1 year of spontaneous amenorrhea (in questionable cases a blood sample with simultaneous levels of follicle stimulating hormone (FSH) above 40 U/L and estradiol below 30 ng/L is confirmatory) Exclusion criteria: Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged 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 50 to 90 mmHg in young subjects, and systolic blood pressure greater than 150 mmHg, diastolic blood pressure greater than 95 mmHg in elderly subjects, or pulse rate outside the range of 50 to 90 bpm Any laboratory value outside the reference range that the investigator considers to be of clinical relevance Any evidence of a concomitant disease judged as clinically relevant by the investigator Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of the gastrointestinal tract that could interfere with kinetics of the trial medication 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 Chronic or relevant acute infections Further exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

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: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 425809 very low dose - part I<br>Part I only - very low dose tablet, oral administration with 240 ml water, over 14 days | Drug: BI 425809<br>* Tablets<br>|
| Placebo Comparator: Placebo - part I<br>Part I only - placebo tablet, oral administration with 240ml water, over 14 days | Drug: Placebo<br>* Tablets<br>|
| Experimental: BI 425809 low dose - part I<br>Part I - low dose tablet, oral administration with 240 ml water, over 14 days | Drug: BI 425809<br>* Tablets<br>|
| Experimental: BI 425809 medium dose - part I<br>Part I only - medium dose tablet, oral administration with 240 ml water, over 14 days | Drug: BI 425809<br>* Tablets<br>|
| Experimental: BI 425809 high dose -part I<br>Part I only - high dose tablet, oral administration with 240 ml water, over 14 days | Drug: BI 425809<br>* Tablets<br>|
| Experimental: BI 425809 low dose - part II<br>Part II - one low dose tablet on day 1 of visit 2 and 2a | Drug: BI 425809<br>* Tablets<br>|
| Experimental: BI 425809 very high dose -part I<br>Part I only - very high dose tablet, oral administration with 240 ml water, over 14 days | Drug: BI 425809<br>* Tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| frequency [N(%)] of subjects with drug related adverse events (AEs) |  | up to 25 days after first drug administration | 
| AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) only part II |  | up to 96 hours | 
| Cmax (maximum measured concentration of the analyte in plasma) only part II |  | up to 96 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum measured concentration of the analyte in plasma) |  | up to 72 hours after first dose | 
| AUCt,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval t) |  | up to 216 hours after last dose | 
| Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval t) |  | up to 216 hours after last dose | 
| AUC0-infinity (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) only part II |  | up to 96 hours | 
| AUCt 0-24(area under the concentration-time curve of the analyte in plasma over a uniform dosing interval t after administration of the first dose) |  | up to 72 hours after first dose |