Safety, Pharmacokinetics and Pharmacodynamics of Single Rising Doses Oral BIRB 796 BS in Healthy Human Subjects

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: Placebo; Drug: BIBR 796 BS; Other: high fat standardized breakfast

• Registration Number: NCT02208856
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

To assess safety, pharmacokinetics and pharmacodynamics of BIRB 796 BS in escalating single doses, with and without a 64 g fat breakfast at one selected dose.

Detailed Description

Not available

Study Timeline

• Study Start: 1999-09
• Primary Completion: 1999-12
• Status Verified: 2014-08
• Study First Submitted: 2014-08-04
• Study First Submitted QC: 2014-08-04
• Last Update Submitted: 2014-08-04
• Study First Posted: 2014-08-05
• Last Update Posted: 2014-08-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 64

Inclusion Criteria

• Healthy male subjects as determined by results of screening
• Signed written informed consent in accordance with good clinical practice (GCP) and local legislation
• Age >= 18 and <= 45 years
• Broca >= -20% and <= +20%

Exclusion Criteria

• Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Surgery of gastrointestinal tract (except appendectomy)
• Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• History of orthostatic hypotension, fainting spells or blackouts
• Chronic or relevant acute infections
• History of allergy/hypersensitivity (including drug allergy) which is deemed relevant ot the trial as judged by the investigator
• Intake of drugs with a long half-life (> 24 hours) (= 1 month prior to administration or during the trial)
• Use of any drugs, which might influence the results of the trial (= 10 days prior to administration or during the trial)
• Participation in another trial with an investigational drug (=2 months prior to administration or during trial)
• Smoker (> 10 cigarettes of > 3 cigars of > 3 pipes/day)
• Inability to refrain from smoking on trial days
• Alcohol abuse (> 60 g/day)
• Drug abuse
• Blood donation > 400 ml (=1 month prior to administration of during the trial)
• Excessive physical activities (= 5 days prior to administration or during the trial)
• Any laboratory value outside the reference range of clinical relevance (but not exclusive to) total white cell count >= 10 x 10**9/L, C-reactive protein >= 4.5 mg/L, any haemoglobin or > 15 mg/dl protein on urine dipstick
• History of any familial bleeding disorder

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
BIBR 796 BS food effect	BIBR 796 BS	-
BIBR 796 BS food effect	high fat standardized breakfast	-
BIBR 796 BS	BIBR 796 BS	-

Primary Outcome Measures

Name	Time	Method
Number of subjects with clinically relevant changes in electrocardiograms (ECG)	Baseline, up to 96 hours after drug administration
Number of subjects with adverse events	up to 96 hours after drug administration
Number of subjects with clinically relevant changes in vital signs	Baseline, up to 96 hours after drug administration
Number of subjects with clinically relevant changes in laboratory measurements	Baseline, up to 96 hours after drug administration

Secondary Outcome Measures

Name	Time	Method
Maximum concentration of the analyte in plasma (Cmax)	up to 48 hours after drug administration
Area under the concentration-time curve of the analyte in plasma from time zero to infinity (AUC0-inf)	up to 48 hours after drug administration
Time from dosing to the maximum concentration of the analyte in plasma (Tmax)	up to 48 hours after drug administration
Terminal rate constant of the analyte in plasma (λz)	up to 48 hours after drug administration
Half life of the analyte in plasma (t1/2)	up to 48 hours after drug administration
Mean residence time of the analyte in the body (MRTtot)	up to 48 hours after drug administration
Mac-1/L selectin ratio of TNFalpha-stimulated to unstimulated neutrophils	up to 48 hours after drug administration
Apparent clearance of the analyte in plasma (CL/F)	up to 96 hours after drug administration
Apparent volume of distribution during the terminal phase λz (Vz/F)	up to 48 hours after drug administration
Mac-1/L selectin ratio of formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated to unstimulated neutrophils	up to 48 hours after drug administration
Percent changes in TNFalpha production	up to 48 hours after drug administration	after ex vivo stimulation of whole blood with endotoxin