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Bioavailability of BIBR 1048 MS Single Doses With or Without Pantoprazole in Healthy Subjects

Phase 1
Completed
Conditions
Healthy
Interventions
Drug: BIBR 1048 MS capsule formulation A
Drug: BIBR 1048 MS capsule formulation B
Drug: BIBR 1048 MS powder plus solution
Registration Number
NCT02170805
Lead Sponsor
Boehringer Ingelheim
Brief Summary

The pharmacokinetics of 50 mg BIBR 1048 administered as two newly developed capsule formulation using melt extrusion technology was assessed in two separate, single dose, 3-way crossover, open design, randomised studies. The 3-way crossover treatments included administration of the tartaric acid solution of 50 mg BIBR 1048, the capsule formulation A or B and administration of the capsules with coadministration of pantoprazole.

Detailed Description

Not available

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 GCP and local legislation
  • Age ≥ 18 and ≤ 55 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 & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Substudy 1BIBR 1048 MS capsule formulation AThree treatments of single administrations of BIBR 1048 MS 50 mg with or without pantoprazole; randomised sequence 1. BIBR 1048 MS capsule formulation A without pantoprazole; 2. BIBR 1048 MS capsule formulation A with coadministration of 40 mg pantoprazole (bid); 3. BIBR 1048 MS powder plus solution without pantoprazole
Substudy 1BIBR 1048 MS powder plus solutionThree treatments of single administrations of BIBR 1048 MS 50 mg with or without pantoprazole; randomised sequence 1. BIBR 1048 MS capsule formulation A without pantoprazole; 2. BIBR 1048 MS capsule formulation A with coadministration of 40 mg pantoprazole (bid); 3. BIBR 1048 MS powder plus solution without pantoprazole
Substudy 2BIBR 1048 MS capsule formulation BThree treatments of single administrations of BIBR 1048 MS 50 mg with or without pantoprazole; randomised sequence 1. BIBR 1048 MS capsule formulation B without pantoprazole; 2. BIBR 1048 MS capsule formulation B with coadministration of 40 mg pantoprazole (bid); 3. BIBR 1048 MS powder plus solution without pantoprazole
Substudy 2BIBR 1048 MS powder plus solutionThree treatments of single administrations of BIBR 1048 MS 50 mg with or without pantoprazole; randomised sequence 1. BIBR 1048 MS capsule formulation B without pantoprazole; 2. BIBR 1048 MS capsule formulation B with coadministration of 40 mg pantoprazole (bid); 3. BIBR 1048 MS powder plus solution without pantoprazole
Substudy 1PantoprazoleThree treatments of single administrations of BIBR 1048 MS 50 mg with or without pantoprazole; randomised sequence 1. BIBR 1048 MS capsule formulation A without pantoprazole; 2. BIBR 1048 MS capsule formulation A with coadministration of 40 mg pantoprazole (bid); 3. BIBR 1048 MS powder plus solution without pantoprazole
Substudy 2PantoprazoleThree treatments of single administrations of BIBR 1048 MS 50 mg with or without pantoprazole; randomised sequence 1. BIBR 1048 MS capsule formulation B without pantoprazole; 2. BIBR 1048 MS capsule formulation B with coadministration of 40 mg pantoprazole (bid); 3. BIBR 1048 MS powder plus solution without pantoprazole
Primary Outcome Measures
NameTimeMethod
AUC0-∞ (Area under the concentration-time curve the time interval from 0 extrapolated to infinity) of BIBR 953 ZWBefore and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 hours after administration of study drug
AUC0-tf (Area under the concentration-time curve over the time interval from 0 to the time of the last quantifiable concentration) of BIBR 953 ZWBefore and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 hours after administration of study drug
Secondary Outcome Measures
NameTimeMethod
Cmax (Maximum measured concentration) of BIBR 953 ZWBefore and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 hours after administration of study drug
tmax (Time from dosing to the maximum concentration) of BIBR 953 ZWBefore and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 hours after administration of study drug
Vz/F (Apparent volume of distribution) of BIBR 953 ZWBefore and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 hours after administration of study drug
t1/2 (Terminal half-life) of BIBR 953 ZWBefore and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 hours after administration of study drug
MRTtot (Total mean residence time) of BIBR 953 ZWBefore and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 hours after administration of study drug
CLtot/F (Total apparent clearance) of BIBR 953 ZWBefore and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 hours after administration of study drug
λz (terminal elimination rate constant) of BIBR 953 ZWBefore and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 hours after administration of study drug
Changes in aPTT (activated partial thromboplastin time)Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 hours after administration of study drug
Changes in PT (prothrombin time)Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 48 hours after administration of study drug
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