Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Doses

Study Overview
=================
Brief Summary
-----------------
The primary objective of this trial was to investigate safety and tolerability of multiple doses of BI 409306 in healthy young and elderly volunteers. The secondary objective was to explore the pharmacokinetics and pharmacodynamics of multiple doses of BI 409306 in healthy young and elderly volunteers

Official Title
-----------------
Safety, Tolerability Pharmacokinetics and Pharmacodynamics of Multiple Rising Doses of BI 409306 Film-coated Tablets Given Orally q.d. or Bid for 14 Days in Young Healthy and Elderly Healthy Male/Female Volunteers (Randomised, Double-blind, Placebo Controlled Within Dose Groups Phase I Study)

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

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Healthy males and females 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 >21 and Age <50 years for young healthy volunteers or Age >65 and Age <80 years for elderly healthy volunteers 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. For female subjects: Female subjects must be surgically sterilized or postmenopausal. Surgical sterilization or hysterectomy must have occurred at least 6 months prior to screening. Menopausal women must have no regular menstrual bleeding for at least 2 years prior to screening. 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 (including but not limited to any kind of seizures, stroke or psychiatric disorders) History or evidence of relevant orthostatic reaction (drop in systolic blood pressure (SBP) >20 mm Hg and increase in heart rate > 30 bpm after 2 minutes standing relative to supine data), fainting spells or blackouts. Chronic or relevant acute infections History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) Intake of any drugs within 14 days or drugs with a long half-life (> 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 four weeks prior to administration or during the trial Smoker (> 5 cigarettes or > 1 cigars or > 1 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 in the judgment of investigator Inability to comply with dietary regimen of trial site A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc F interval >430 ms in males and >450 ms in females); A history of additional risk factors for TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 409306 low dose<br>Film-coated tablet | Drug: BI 409306<br>* Low dose film-coated tablet<br>|
| Experimental: BI 409306 medium dose<br>Film-coated tablet | Drug: BI 409306<br>* Medium dose film-coated tablet<br>|
| Experimental: BI 409306 high dose<br>Film-coated tablet | Drug: BI 409306<br>* High dose film-coated tablet<br>|
| Experimental: BI 409306 high dose II<br>Film-coated tablet | Drug: BI 409306<br>* High dose film-coated tablet<br>|
| Placebo Comparator: Placebo<br>Film-coated tablet | Drug: BI 409306 Placebo<br>* Placebo film-coated tablet<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events |  | up to 12 weeks | 
| Number of participants with clinically relevant findings in vital signs |  | up to 12 weeks | 
| Number of participants with clinically significant abnormalities in electrocardiogram (ECG) results |  | up to 12 weeks | 
| Number of participants with significant changes from baseline laboratory measurements |  | up to 12 weeks | 
| Number of participants with clinically relevant findings in physical examination |  | up to 12 weeks | 
| Assessment of tolerability by investigator (global assessment) |  | up to 12 weeks | 
| Suicidality assessment |  | up to 12 weeks | 
| Color discrimination test |  | up to 12 weeks | 
| Visual acuity test |  | up to 12 weeks | 
| Ophthalmological examination |  | up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum measured concentration of the analyte in plasma) |  | up to 12 weeks | 
| tmax (time from dosing to maximum measured concentration of the analyte in plasma) |  | up to 12 weeks | 
| AUC0-24 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to 24 hours) |  | up to 12 weeks | 
| AUC0-12 (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to 12 hours) |  | up to 12 weeks |