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

Phase 1

Completed

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

• Registration Number: NCT02211157
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study Start: 2000-03
• Primary Completion: 2000-07
• Status Verified: 2014-08
• Study First Submitted: 2014-08-05
• Study First Submitted QC: 2014-08-05
• Study First Posted: 2014-08-07
• Last Update Submitted: 2014-08-07
• Last Update Posted: 2014-08-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 24

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
BIBR 796 BS, fasted	BIBR 796 BS	dose escalation
BIBR 796 BS, fed	BIBR 796 BS	50 mg BIRB 796 BS (food effect)
BIBR 796 BS, fed	high fat breakfast	50 mg BIRB 796 BS (food effect)
Placebo	Placebo	-

Primary Outcome Measures

Name	Time	Method
Number of patients with clinically relevant changes in vital signs	up to 16 days
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

Secondary Outcome Measures

Name	Time	Method
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)	up to day 9	Change in the Mac-1 / L-selectin ratio
Assessment of neutrophil and monocyte activation by ex vivo stimulation of whole blood with tumour necrosis factor (TNF) α	up to day 9	Change in the Mac-1 / L-selectin ratio
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