Tolerability of BIBR 953 ZW IV and Bioavailability of BIBR 1048 Tablet and Solution in Healthy Males

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: BIBR 1048 MS tablet; Drug: BIBR 953 ZW IV Placebo; Drug: BIBR 953 ZW IV; Drug: BIBR 1048 MS oral solution

• Registration Number: NCT02170584
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

Two substudies to assess (1) the tolerability of BIBR 953 ZW intravenous infusion at 0.1, 1 and 5 mg BIBR 953 ZW and (2) the absolute bioavailability of 100mg BIBR 1048 administered as 'acid free' tablet formulation (TF1) and (3) the bioavailability of the 100 mg tablet of BIBR 1048 relative to the tartaric acid solution of 100 mg dose strength and (4) the absolute bioavailability of the 100 mg tartaric acid solution of BIBR 1048 MS.

Detailed Description

Not available

Study Timeline

• Study Start: 2001-01
• Primary Completion: 2001-03
• Status Verified: 2014-06
• Study First Submitted: 2014-06-20
• Study First Submitted QC: 2014-06-20
• Last Update Submitted: 2014-06-20
• Study First Posted: 2014-06-23
• Last Update Posted: 2014-06-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 30

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%

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
BIBR 1048 MS tablet	BIBR 1048 MS tablet	-
BIBR 953 ZW IV Placebo	BIBR 953 ZW IV Placebo	-
BIBR 953 ZW IV	BIBR 953 ZW IV	-
BIBR 1048 MS oral solution	BIBR 1048 MS oral solution	-

Primary Outcome Measures

Name	Time	Method
AUC0-inf (Area under the plasma concentration-time curve extrapolated to infinity)	up to 48 hours after drug administration
AUC0-tf (Area under the plasma concentration-time curve up to the last quantifiable plasma concentration)	up to 48 hours after drug administration
Cmax (Maximum plasma concentration after oral administration)	up to 48 hours after drug administration
Cumulative urinary excretion of BIBR 953 ZW administered intravenously	up to 48 hours after drug administration

Secondary Outcome Measures

Name	Time	Method
changes in activated partial thromboplastin time (aPTT )	up to 48 hours after drug administration
changes in prothrombin time (PT)	up to 48 hours after drug administration
C29 (Plasma concentration of BIBR 953 ZW at 29 minutes after the start of the 30 min. infusion)	29 minutes after start of infusion
t1/2 (terminal half-life)	up to 48 hours after infusion
CLtot (total clearance of drug from plasma)	up to 48 hours after infusion
CLren (renal clearance from plasma)	up to 48 hours after infusion
MRTdisp (Mean time of residence of drug molecules in the body after intravascular administration)	up to 48 hours after infusion
Vss (apparent volume of distribution at steady state)	up to 48 hours after infusion
Vz (Apparent volume of distribution during the terminal elimination phase)	up to 48 hours after infusion
MRTtot (total mean residence time)	up to 48 hours after oral administration
CLtot/F (total clearance after oral administration)	up to 48 hours after oral administration
tmax (time to reach the peak plasma concentration)	up to 48 hours after oral administration
Vz/F (apparent volume of distribution of the terminal elimination phase after oral administration)	up to 48 hours after oral administration
changes in Ecarin clotting time (ECT)	up to 48 hours after drug administration
changes in thrombin time (TT)	up to 48 hours after drug administration
changes in vital signs (systolic and diastolic blood pressure, pulse rate)	up to 1 month
changes in electrocardiogram	up to 1 month
occurrence of adverse events	up to 1 month