Safety, Tolerance, and Pharmacokinetics of Single Rising Oral Doses of BILB 1941 ZW Solution in Healthy Male Subjects, Followed With Bioavailability Comparison of BILB 1941 ZW Tablet and Solution Formulation Administered With or Without Food

Phase 1

Completed

Interventions: Drug: BILB 1941 ZW - single rising dose part
Drug: Placebo
Drug: BILB 1941 ZW - tablet
Drug: BILB 1941 ZW - solution
Other: standardized breakfast

Brief Summary: The objective of the current study was to investigate the safety, tolerability, and pharmacokinetics of BILB 1941 ZW following the administration of single rising doses from 5 mg to 300 mg. In addition the bioavailability of the 60 mg dose given fasted and after a high-fat breakfast was to be be investigated

Recruitment & Eligibility

Inclusion Criteria

Healthy males according to the following criteria based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests:

1.1 No finding deviating from normal and of clinical relevance

1.2 No evidence of a clinically relevant concomitant disease
Age ≥18 and Age ≤50 years, 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

Exclusion Criteria

Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
History or current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hormonal disorders, including a clinical history of viral hepatitis, or serological evidence of active Hepatitis B or Hepatitis C infection
History of orthostatic hypotension, fainting spells and blackouts
Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
Chronic or relevant acute infections
History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
Intake of drugs with a long half-life (> 24 hours) within 1 month prior to administration
Use of any drugs which might influence the results of the trial within 10 days prior to administration or during the trial
Participation in another trial with an investigational drug within 1 month prior to administration or during the trial
Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from smoking on trial days
Alcohol abuse (> 60 g/day)
Drug abuse
Blood donation of more than 100 mL within 1 month prior to administration or during the trial
Excessive physical activities within 5 days prior to administration or during the trial
Any laboratory value outside the clinically accepted reference range and of clinical relevance
History of any familial bleeding disorder

Arm && Interventions

Group	Intervention	Description
BILB 1941 ZW - single rising dose	BILB 1941 ZW - single rising dose part	Single rising dose part
Placebo	Placebo	Single rising dose part
BILB 1941 ZW - tablet - fasted	BILB 1941 ZW - tablet	Relative bioavailability: The oral solution fasted should be compared with the solid form fasted and after a standardized breakfast
BILB 1941 ZW - solution	BILB 1941 ZW - solution	Relative bioavailability: The oral solution fasted should be compared with the solid form fasted and after a standardized breakfast
BILB 1941 ZW - tablet - fed	BILB 1941 ZW - tablet	Relative bioavailability: The oral solution fasted should be compared with the solid form fasted and after a standardized breakfast
BILB 1941 ZW - tablet - fed	standardized breakfast	Relative bioavailability: The oral solution fasted should be compared with the solid form fasted and after a standardized breakfast

Primary Outcome Measures

Name	Time	Method
Number of subjects with clinically significant changes in vital signs	up to 48 hours following drug administration	Blood pressure, Pulse Rate
Number of subjects with adverse events	up to 48 hours following drug administration
Assessment of tolerability by investigator on a 4-point scale	after 48 hours following drug administration
Number of subjects with abnormal findings in physical examination	up to 48 hours following drug administration
Number of subjects with abnormal changes in laboratory parameters	up to 48 hours following drug administration
Number of subjects with clinically significant changes in 12-lead ECG (electrocardiogram)	up to 48 hours following drug administration

Secondary Outcome Measures

Name	Time	Method
tmax (time from dosing to maximum concentration)	up to 48 hours following drug administration
AUC0-∞ (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)	up to 48 hours following 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)	up to 48 hours following drug administration
t1/2 (terminal half-life of the analyte in plasma)	up to 48 hours following drug administration
Cmax (maximum concentration of the analyte in plasma)	up to 48 hours following drug administration
λz (terminal rate constant in plasma)	up to 48 hours following drug administration
MRT (Mean time of residence of drug molecules in the body after intravascular administration)	up to 48 hours following drug administration
Vz/F (Apparent volume of distribution during the terminal phase after extravascular administration)	up to 48 hours following drug administration