Safety, Pharmacokinetics and Pharmacodynamics of BIRB 796 BS Tablets Administered to Healthy Human Subjects

Safety, Pharmacokinetics and Pharmacodynamics of BIRB 796 BS Tablets (20, 30, 150, 300, and 600 mg) Administered Orally to Healthy Human Subjects Once Daily for 7 Days. A Placebo Controlled, Randomised, Double Blinded Study

Study to assess safety, pharmacokinetics and pharmacodynamics of BIRB 796 BS in escalating multiple doses with and without a 64 g fat breakfast at the 50 mg dose level

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 41 years (Adult)
• Accepts Healthy Volunteers: No
• 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 and local legislation
• Age ≥ 18 and ≤ 45 years
• Broca ≥ - 20% and ≤ + 20%

Exclusion Criteria:

• Any findings of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hormonal disorders
• Surgery of gastrointestinal tract (except appendectomy)
• 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 or during the trial)
• Use of any drugs which might influence the results of the trial within 10 days prior to administration or during trial
• Participation in another trial with an investigational drug within 2 months prior to administration or during trial
• Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day)
• Inability to refrain from smoking on study days
• Alcohol abuse (> 60 g/day)
• Drug abuse
• Blood donation > 400 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 reference range of clinical relevance including, but not limited to total white cell count ≥ 10 x 10**9/L, C-reactive protein ≥ 4.5 mg/L, Gamma-Glutamyl Transferase ≥ 40 U/L, any hemoglobin or > 15 mg/dl protein or urine dipstick, abnormal Multitest® assessment of cellular immunity
• History of any familial bleeding disorder
• Inability to comply with dietary regimen of study centre

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, fasted; dose escalation	Drug: BIBR 796 BS
Experimental: BIBR 796 BS, fed; 50 mg BIRB 796 BS (food effect)	Drug: BIBR 796 BS; Other: high fat breakfast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients with clinically relevant changes in laboratory parameters	up to day 16
Number of patients with abnormal findings in electrocardiogram (ECG)	up to day 16
Number of patients with adverse events	up to 30 days
Assessment of tolerability on a 4-point scale	day 16
Number of patients with clinically relevant changes in vital signs	up to 16 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum plasma concentration (Cmax) for several time points		up to day 9
Area under the plasma concentration-time curve (AUC) for several time points		up to day 9
Time to maximum concentration (tmax)		up to day 9
Elimination rate constant (λz)		up to day 9
Terminal half-life (t1/2)		up to day 9
Mean residence time (MRT)		up to day 9
Apparent clearance (CL/f)		up to day 9
Apparent volume of distribution (Vz/F)		up to day 9
Assessment of neutrophil and monocyte activation by ex vivo stimulation of whole blood with formyl-methionyl-leucyl-phenylalanine (fMLP)	Change in the Mac-1 / L-selectin ratio	up to day 9
Assessment of neutrophil and monocyte activation by ex vivo stimulation of whole blood with tumour necrosis factor (TNF) α	Change in the Mac-1 / L-selectin ratio	up to day 9
Assessment of TNFα production by ex vivo stimulation of whole blood with endotoxin		up to day 9
Changes in cellular immune response measured by Multitest®		Day 8

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2000
• Primary Completion (Actual): July 1, 2000

Study Registration Dates

• First Submitted: August 5, 2014
• First Submitted That Met QC Criteria: August 5, 2014
• First Posted (Estimate): August 7, 2014

Study Record Updates

• Last Update Posted (Estimate): August 8, 2014
• Last Update Submitted That Met QC Criteria: August 7, 2014
• Last Verified: August 1, 2014

More Information

Terms related to this study

• Other Study ID Numbers: 1175.3