Single Increasing Doses of BIII 890 CL in Healthy Young Male Volunteers and in Healthy Elderly Male and Female Volunteers

Study Overview
=================
Brief Summary
-----------------
Safety, tolerability and pharmacokinetics of BIII 890

Official Title
-----------------
A Single Blind, Placebo-controlled, Parallel-group, Single Increasing Dose Tolerance Study in Healthy Young Male Volunteers After Intravenous Administration of BIII 890 CL as Loading Dose (Dosage: 12.5, 25, 50 mg/h, Infusion Time 1 hr; 50 mg/h, Infusion Time 2 Hrs) Followed by Maintenance Dose (Dosage: 6.25, 12.5, 25 mg/h, Infusion Time 5 Hrs; 30 mg/h, Infusion Time 4 Hrs) and in Healthy Elderly Male and Female Volunteers After Intravenous Administration of BIII 890 CL as Loading Dose (Dosage: 50 mg/h, Infusion Time 1 hr) Followed by Maintenance Dose (Dosage: 25 mg/h, Infusion Time 5 Hrs)

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

Intervention / Treatment
-----------------
* Drug: BIII 890 CL
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants in the study should be healthy males, range from 21 to 50 years of age and be within +- 20% of their normal weight (Broca-Index) and healthy elderly males and females, > 60 years of age and be within +-25 % of their normal weight (Broca-Index) In accordance with good clinical practice (GCP) and the local legislation all volunteers will have given their written informed consent prior to admission to the study Exclusion Criteria: Volunteers were excluded from the study if the results of the medical examination, laboratory tests or ECG recordings are judged by the investigator to differ significantly from normal clinical values Volunteers with known gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Volunteers with diseases of the central nervous system (such as epilepsy), central nervous system (CNS) trauma in their medical history or with psychiatric disorders or neurological disorders Volunteers with known history of relevant orthostatic hypotension, fainting spells or blackouts Volunteers with chronic or relevant acute infections Volunteers with history of allergy/hypersensitivity (including drug allergy) which was deemed relevant to the trial as, judged by the investigator Volunteers who had taken a drug with a long half-life (≥ 24 hours) within at least one month or less than ten half-lives of the respective drug before enrolment in the study Volunteers who received any other drugs which could influence the results of the trial during the week prior to the start of the study Volunteers who participated in another study with an investigational drug within the last two months preceding this study Volunteers who smoke (> 10 cigarettes or 3 cigars or 3 pipes/day) Volunteers who were not able to refrain from smoking on study days Volunteers who drunk more than 60 g of alcohol per day Volunteers who were dependent on drugs Volunteers who participated in excessive physical activities (e.g. competitive sports) during the last week before the study Volunteers who donated blood within the last 4 weeks (≥ 100 mL)

Ages Eligible for Study
-----------------
Minimum Age: 21 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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIII 890 CL single rising dose<br> | Drug: BIII 890 CL<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with clinically relevant changes in vital signs | blood pressure, pulse rate, respiratory rate, body temperature | Pre-dose, up to 8 days after drug administration | 
| Number of subjects with clinically relevant changes in 12-lead ECG |  | Pre-dose, up to 8 days after drug administration | 
| Number of subjects with clinically relevant changes in laboratory parameters | including coagulation parameters | Pre-dose, up to 8 days after drug administration | 
| Number of subjects with adverse events |  | Up to 8 days after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum measured concentration of the analyte in plasma (Cmax) |  | up to 32 hours after start of drug administration | 
| Time from dosing to the maximum concentration of the analyte in plasma over a uniform dosing interval λz (tmax) |  | up to 32 hours after start of drug administration | 
| Apparent terminal half-life of the analyte in plasma (t1/2) |  | up to 32 hours after start of drug administration | 
| Area under the concentration-time curve of the analyte in plasma (AUC) |  | up to 32 hours after start of drug administration | 
| Mean residence time (MRT) |  | up to 32 hours after start of drug administration | 
| Plasma clearance (CL) |  | up to 32 hours after start of drug administration | 
| Volume of distribution (V) |  | up to 32 hours after start of drug administration | 
| Amount of parent drug excreted into urine (Ae) |  | up to 32 hours after start of drug administration |