Clinical trial NCT02170584: Tolerability of BIBR 953 ZW IV and Bioavailability of BIBR 1048 Tablet and Solution in Healthy Males
Official title: Tolerability of Single Rising Doses of 0.1 mg, 1 mg, and 5 mg BIBR 953 ZW IV (Placebo-controlled in Each Dose Group; Substudy 1) and Absolute and Relative Bioavailability of 100mg BIBR 1048 Tablet and of Solution and of 1 mg or 5 mg BIBR 953 ZW IV (Randomized, Three-way Crossover; Substudy 2).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-06-23
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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 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

Primary outcomes:
measure: AUC0-inf (Area under the plasma concentration-time curve extrapolated to infinity)
timeFrame: up to 48 hours after drug administration
measure: AUC0-tf (Area under the plasma concentration-time curve up to the last quantifiable plasma concentration)
timeFrame: up to 48 hours after drug administration
measure: Cmax (Maximum plasma concentration after oral administration)
timeFrame: up to 48 hours after drug administration
measure: Cumulative urinary excretion of BIBR 953 ZW administered intravenously
timeFrame: up to 48 hours after drug administration
Secondary outcomes:
measure: changes in activated partial thromboplastin time (aPTT )
timeFrame: up to 48 hours after drug administration
measure: changes in prothrombin time (PT)
timeFrame: up to 48 hours after drug administration
measure: C29 (Plasma concentration of BIBR 953 ZW at 29 minutes after the start of the 30 min. infusion)
timeFrame: 29 minutes after start of infusion
measure: t1/2 (terminal half-life)
timeFrame: up to 48 hours after infusion
measure: CLtot (total clearance of drug from plasma)
timeFrame: up to 48 hours after infusion
measure: CLren (renal clearance from plasma)
timeFrame: up to 48 hours after infusion
measure: MRTdisp (Mean time of residence of drug molecules in the body after intravascular administration)
timeFrame: up to 48 hours after infusion
measure: Vss (apparent volume of distribution at steady state)
timeFrame: up to 48 hours after infusion
measure: Vz (Apparent volume of distribution during the terminal elimination phase)
timeFrame: up to 48 hours after infusion
measure: MRTtot (total mean residence time)
timeFrame: up to 48 hours after oral administration
measure: CLtot/F (total clearance after oral administration)
timeFrame: up to 48 hours after oral administration
measure: tmax (time to reach the peak plasma concentration)
timeFrame: up to 48 hours after oral administration
measure: Vz/F (apparent volume of distribution of the terminal elimination phase after oral administration)
timeFrame: up to 48 hours after oral administration
measure: changes in Ecarin clotting time (ECT)
timeFrame: up to 48 hours after drug administration
measure: changes in thrombin time (TT)
timeFrame: up to 48 hours after drug administration
measure: changes in vital signs (systolic and diastolic blood pressure, pulse rate)
timeFrame: up to 1 month
measure: changes in electrocardiogram
timeFrame: up to 1 month
measure: occurrence of adverse events
timeFrame: up to 1 month
Other outcomes:
Locations:
Study officials:
References: