Multiple Oral Doses of BIBR 1048 MS Solution in Healthy Volunteers

Safety, Pharmacodynamics, and Pharmacokinetics After Multiple Oral Doses of 50, 100, 200, and 400 mg BIBR 1048 MS Solution Administered TID for 7 Days to Healthy Volunteer Subjects. An Open Study, Placebo-controlled Randomised Double Blind at Each Dose Level

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BIBR 1048 MS low; Drug: BIBR 1048 MS medium 1; Drug: BIBR 1048 MS medium 2; Drug: BIBR 1048 MS high; Drug: BIBR 1048 MS placebo

• Study Type: Interventional
• Enrollment (Actual): 40
• 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 GCP 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
• 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
  • any bleeding disorder including prolonged or habitual bleeding
  • other hematologic disease
  • cerebral bleeding (e.g. after a car accident)
  • commotio cerebri
• Intake of drugs with a long half-life (>24 hours) within 1 month prior to administration
• 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) or inability to refrain from smoking on study days
• Alcohol abuse (> 60 g/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 familial bleeding disorder
• Thrombocytes < 150000/µl

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BIBR 1048 MS low dose	Drug: BIBR 1048 MS low
Experimental: BIBR 1048 MS high dose	Drug: BIBR 1048 MS high
Experimental: BIBR 1048 MS medium dose 1	Drug: BIBR 1048 MS medium 1
Experimental: BIBR 1048 MS medium dose 2	Drug: BIBR 1048 MS medium 2
Placebo Comparator: BIBR 1048 Placebo	Drug: BIBR 1048 MS placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in aPTT (activated partial thromboplastin time)	up to day 10
Change in PT (prothrombin time)	up to day 10

Secondary Outcome Measures

Outcome Measure	Time Frame
Cmax (maximum measured concentration) of BIBR 953 ZW	up to day 10
tmax (time from dosing to the maximum concentration) of BIBR 953 ZW	up to day 10
AUC0-∞ (area under the concentration-time curve the time interval from 0 extrapolated to infinity) of BIBR 953 ZW	up to day 10
Cmax,ss (maximum measured concentration at steady state) of BIBR 953 ZW	Day 7
Cmin,ss (minimum measured concentration at steady state) of BIBR 953 ZW	Day 7
Cavg (average plasma concentration at steady state) of BIBR 953 ZW	up to day 10
PTF (percent peak trough fluctuation for the last dosing interval) of BIBR 953 ZW	up to day 10
tmax,ss (time to reach Cmax) of BIBR 953 ZW	up to day 10
t1/2 (terminal half-life) of BIBR 953 ZW	up to day 10
AUCss (area under the plasma concentration-time curve of one dosing interval at steady state) of BIBR 953 ZW	up to day 10
MRTss (mean residence time at steady state) of BIBR 953 ZW	up to day 10
CLtot/F (total apparent clearance) of BIBR 953 ZW	up to day 10
Vz/F (apparent volume of distribution) of BIBR 953 ZW	up to day 10

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: May 1, 1999
• Primary Completion (Actual): July 1, 1999

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; Protease Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Dabigatran
• Other Study ID Numbers: 1160.2