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

Safety, Pharmacokinetics and Pharmacodynamics of Single Rising Doses (1, 4, 15, 50, 100, 200, 400, and 600 mg) Oral BIRB 796 BS in Healthy Human Subjects. A Placebo Controlled, Randomised Study, Double Blinded at Each Dose Level

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BIBR 796 BS; Other: high fat standardized breakfast

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: BIBR 796 BS food effect	Drug: BIBR 796 BS; Other: high fat standardized breakfast
Experimental: BIBR 796 BS	Drug: BIBR 796 BS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
Number of subjects with clinically relevant changes in electrocardiograms (ECG)	Baseline, up to 96 hours after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Mac-1/L selectin ratio of TNFalpha-stimulated to unstimulated neutrophils		up to 48 hours after drug administration
Percent changes in TNFalpha production	after ex vivo stimulation of whole blood with endotoxin	up to 48 hours after drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: September 1, 1999
• Primary Completion (Actual): December 1, 1999

Study Registration Dates

• First Submitted: August 4, 2014
• First Submitted That Met QC Criteria: August 4, 2014
• First Posted (Estimate): August 5, 2014

Study Record Updates

• Last Update Posted (Estimate): August 5, 2014
• Last Update Submitted That Met QC Criteria: August 4, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: 1175.1