Clinical trial NCT02170116: Pharmacodynamics, Safety and Pharmacokinetics After Oral Administration of BIBR 1048 MS in Healthy Volunteers
Official title: Pharmacodynamics, Safety and Pharmacokinetics After Single Oral Administration of 10, 30, 100, 200 and 400 mg BIBR 1048 MS as Drinking Solution in Healthy Subjects. An Open Study, Placebo Randomized Double Blind at Each Dose Level.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-06-23
Enrollment: 40
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study was to assess safety, pharmacokinetics and the effect of BIBR 953 ZW on coagulation parameters of BIBR 953 ZW after oral single doses of the prodrug, BIBR 1048 MS, in healthy male subjects. This was the first administration of this substance to humans.


Eligibility criteria: Inclusion Criteria:

* Healthy male subjects as determined by results of screening
* Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation
* Age \>= 18 and \<= 45 years
* Broca \>= - 20 % and \<= + 20 %

Exclusion Criteria:

* Any finding 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 or 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)
  * commotion 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 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 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: Changes from baseline in prothrombin time (PT) (International Normalised Ratio (INR))
timeFrame: - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours after administration
measure: Changes from baseline in activated partial thromboplastin time (aPTT)
timeFrame: - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours after administration
Secondary outcomes:
measure: Peak (maximum) plasma concentration (Cmax) of BIBR 953 ZW
timeFrame: - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration
measure: time to reach the peak plasma concentration (tmax ) of BIBR 953 ZW
timeFrame: - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration
measure: AUC0-12 h - Area under the plasma concentration-time curve of BIBR 953 ZW from 0 to 12 h
timeFrame: - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration
measure: Area under the plasma concentration-time curve (AUC0-infinity) of BIBR 953 ZW from 0 to infinity
timeFrame: - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration
measure: Area under the plasma concentration-time curve of BIBR 953 ZW (AUCtf -infinity) from tf (last time point when measured plasma concentration) to infinity expressed as % of AUC0-infinity
timeFrame: - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration
measure: Terminal half-life(t1/2 ) of BIBR 953 ZW derived from non-compartmental analysis
timeFrame: - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration
measure: Total mean residence time (MRTtot ) of BIBR 953 ZW
timeFrame: - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration
measure: Total clearance (CLtot /f ) of BIBR 953 ZW after oral administration
timeFrame: 24 hours after administration
measure: Volume of distribution (Vz/f ) of BIBR 953 ZW during terminal phase after oral administration
timeFrame: - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration
measure: Changes from baseline in Pulse rate
timeFrame: up to day 3
measure: Changes from baseline in Systolic and diastolic blood pressure
timeFrame: up to day 3
measure: Occurrence of Adverse events
timeFrame: up to day 3
measure: Changes from baseline in Ecarin Clotting Time (ECT)
timeFrame: up to day 3
measure: Changes from baseline in thrombin inhibition test time
timeFrame: up to day 3
measure: Changes from baseline in thrombin time
timeFrame: up to day 3
Other outcomes:
Locations:
Study officials:
References: