Bioavailability of BIBR 953 ZW After BIBR 1048 (Oral Pro-drug of BIBR 953 ZW) Administered as Hydroxypropyl Methylcellulose (HPMC) Polymorph II Capsule Relative to HPMC Polymorph I Capsule in Healthy Subjects.

Bioavailability of BIBR 953 ZW After 150 mg of BIBR 1048 (Oral Pro-drug of BIBR 953 ZW) Administered as HPMC Polymorph II Capsule Relative to 150 mg HPMC Polymorph I Capsule in Healthy Subjects. A Two-way Crossover, Randomised, Open Trial

Investigation of the relative bioavailability of BIBR 953 ZW after administration of 150 mg BIBR 1048 polymorph II versus BIBR 953 ZW after administration of 150 mg BIBR 1048 polymorph I in HPMC capsules

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: BIBR 1048 MS polymorph II; Drug: BIBR 1048 MS polymorph I

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy female and male subjects as determined by results of screening
• Signed written informed consent in accordance with GCP and local legislation
• Age ≥ 18 and ≤ 55 years
• BMI ≥ 18.5 and ≤ 29.9 kg/m2

Exclusion Criteria:

• Any finding at the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
• History of or current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hormonal disorders
• History of relevant 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 that might influence the results of the trial within 10 days prior to administration or during the 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 of more than 400 ml within 4 weeks 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
• History of any familial bleeding disorder
• Platelets < 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 polymorph II	Drug: BIBR 1048 MS polymorph II
Active Comparator: BIBR 1048 MS polymorph I	Drug: BIBR 1048 MS polymorph I

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC0-infinity (area under the plasma concentration-time curve of BIBR 953 ZW from 0 to infinity)	0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration
AUC0-tz	0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration
Cmax (maximum measured plasma concentration of BIBR 953 ZW)	0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration

Secondary Outcome Measures

Outcome Measure	Time Frame
tmax (time from dosing to when the plasma concentration reaches Cmax after extravascular doses )	0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration
t1/2 (half life)	0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration
MRTpo (mean time of residence of drug molecules in the body)	0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration
CL/F (apparent clearance after oral administration)	0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration
Vz/F (apparent volume of distribution)	0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration
Changes in ECG	up to 31 days
Changes in systolic and diastolic blood pressure	up to 31 days
Occurrence of adverse events	up to 31 days
Assessment of tolerability by investigator on a four-point scale	up to 31 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): August 1, 2004

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: 1160.52