Assessment of Safety, Pharmacokinetics and the Effect of BIBR 1048 MS on Coagulation Parameters in Healthy Volunteer Subjects

Bioavailability of BIBR 953 ZW After Multiple Oral Doses of 50 and 200 mg BIBR 1048 MS Film-coated Tablet Administered BIDfor 3 Days or 200 mg BIBR 1048 MS With and Without Pre-treatment With Pantoprazole to Healthy Volunteer Subjects. Two Groups, 2-way Crossover, Randomised, Open Trial

To assess safety, pharmacokinetics and the effect of BIBR 1048 MS on coagulation parameters in healthy volunteer subjects.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BIBR 1048 MS - low dose; Drug: BIBR 1048 MS - high dose; Drug: BIBR 1048 MS + Pantoprazole

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 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 GCP and local legislation
• Age ≥ 18 and ≤ 50 years
• Broca ≥ - 20% and ≤ + 20%

Exclusion Criteria:

• Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram (ECG)) deviating from normal and of clinical relevance
• History or current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hormonal disorders
• History of orthostatic hypotension, fainting spells and blackouts
• Diseases of the central nervous system (such as epilepsy) or psychiatric 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
• History of any bleeding disorder including prolonged or habitual bleeding
• History of other hematologic disease
• History of cerebral bleeding (e.g. after a car accident)
• History of commotio cerebri
• Intake of drugs with a long-life (> 24 hours) within 1 month prior to administration
• Use of any drug which might influence the results of the trial within 10 days prior to administration or during the trial
• Participation in another trial with investigational drug within 2 months prior to administration or during the trial
• Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from smoking on study days
• Alcohol abuse (> 60g/day)
• Drug abuse
• Blood donation 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
• History of any familiar bleeding disorder
• Thrombocytes < 150000/µl

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIBR 1048 MS	Drug: BIBR 1048 MS - low dose; Drug: BIBR 1048 MS - high dose
Experimental: BIBR 1048 MS + Pantoprazole	Drug: BIBR 1048 MS - high dose; Drug: BIBR 1048 MS + Pantoprazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Urinary excretion of total BIBR 953 ZW	Day 1, day 2, day 3 (different time points)
Peak (maximum) plasma concentration at steady state (Cmax,ss) of BIBR 953 ZW	Day 1, day 2, day 3 (different time points)
Area under the plasma concentration-time curve at steady state (AUCss) of BIBR 953 ZW	Day 1, day 2, day 3 (different time points)
Amount of total (free and glucuronide) BIBR 953 ZW excreted in urine over one dosing interval	Day 1, day 2, day 3 (different time points)

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to reach the peak plasma concentration (Tmax,ss) of BIBR 953ZW	Day 1, day 2, day 3 (different time points)
Total clearance (CLtot /f ) of BIBR 953 ZW after oral administration	Day 1, day 2, day 3 (different time points)
Occurence of adverse events	6 weeks
Change from Baseline in pulse rate	Baseline, day 1,day 2, day 3, day 4
Change from Baseline in systolic and diastolic blood pressure	Baseline, day 1,day 2, day 3, day 4
Change from Baseline in clinical laboratory tests	Baseline, day 1,day 2, day 3, day 4
Changes from baseline in activated partial thromboplastin time (aPTT)	Day 1, day 2, day 3 (different time points)
Changes from baseline in prothrombin time (PT) (International Normalised Ratio (INR))	Day 1, day 2, day 3 (different time points)
Total mean residence time (MRTtot) of BIBR 953 ZW after oral administration	ay 1, day 2, day 3 (different time points)

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 1999
• Primary Completion (Actual): January 1, 2000

Study Registration Dates

• First Submitted: June 20, 2014
• First Submitted That Met QC Criteria: June 20, 2014
• First Posted (Estimate): June 23, 2014

Study Record Updates

• Last Update Posted (Estimate): June 23, 2014
• Last Update Submitted That Met QC Criteria: June 20, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Anti-Ulcer Agents; Proton Pump Inhibitors; Dabigatran; Pantoprazole
• Other Study ID Numbers: 1160.14