Safety, Pharmacokinetics and Pharmacodynamics After Single Rising Oral Doses of BIBR 1048 MS as Capsules in Healthy Subjects of Japanese and Caucasian Origin

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Placebo of BIBR 1048 MS; Drug: BIBR 1048 MS

Study type: Interventional

Funder types: Industry

Identifiers

NCT02170844

1160.28

Details and patient eligibility

About

To investigate and compare safety, pharmacokinetics and pharmacodynamics of BIBR 1048 MS following oral administration of single rising doses from 50 mg to 350 mg in healthy male subjects of Japanese and Caucasian origin. This was the first administration of this substance to subjects of Japanese origin.

Enrollment: 40 patients

Sex: Male

Ages: 20 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy males according to the following criteria:

   Based upon a complete medical history, including the physical examination, vital signs (BP, PR, Respiratory Rate and tympanic body temperature), 12- lead ECG, clinical laboratory tests

   • 1.1. No finding deviating from normal and of clinical relevance
   • 1.2. No evidence of a clinically relevant concomitant disease

2. Age ≥20 and Age ≤45 years

3. BMI ≥18 and BMI ≤25 kg/m2 (Body Mass Index)

4. Japanese subjects were from a well-defined Japanese population, both parents of Japanese origin and the subjects have Japanese passport and had lived ≤ 8 years outside Japan.

5. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation.

Exclusion criteria

1. Current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders

2. An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women, or an unwillingness if the male subject to use an adequate form of contraception as well as having their female partner(s) use another form of contraception (if the woman could become pregnant) from the time of the first dose administration until after follow up

3. Current diseases of the central nervous system (such as epilepsy), or psychiatric disorders or neurological disorders

4. History of clinically significant orthostatic hypotension, clinically significant current or past fainting spells or blackouts.

5. Chronic or relevant acute infections

6. 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)
   • concussions (head trauma resulting in injuring to brain) with or without loss of consciousness

7. Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives, whichever is shorter, of the respective drug prior to administration or during the trial

8. Use of Acetylsalicylic-Acid (ASA)-containing over-the-counter medications, clopidogrel or ticlopidine or dipyridamole, chronic administration of Non Steroidal Antiinflammatory Drugs (NSAIDs) (COX-2 inhibitors excluded), coumadin like anticoagulants, chronic use of corticosteroids, heparin and fibrinolytic agents within 14 days prior to administration or during the trial.

9. Use of all other medication including over the counter (medicinal cream, vitamin, eye drop etc.) within 7 days prior to administration or during the trial.

10. Participation in another trial with an investigational drug within three months prior to administration or during the trial

11. Smoker (> 10 cigarettes/day or > 3 cigars/day or > 3 pipes/day)

12. Inability to refrain from smoking on trial days

13. Alcohol abuse (more than 21unit/week)

14. History of drug abuse

15. Blood donation (more than 100 mL within three months prior to screening administration and any blood donation from screening to follow-up)

16. Excessive physical activities (within one week prior to administration or during the trial and until follow-up)

17. Any laboratory value outside the reference range that is of clinical relevance

18. Inability to comply with dietary regimen of study centre

19. Known hypersensitivity to the drug or its excipients

    Exclusion criteria specific for this study:

20. History of any familial bleeding disorder

21. Thrombocytes < 150000/micro L

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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40 participants in 4 patient groups, including a placebo group

BIBR 1048 MS (Japanese)

Experimental group

Description:

Japanese subjects received an increasing dose (50 mg to 150 mg) of BIBR 1048 MS

Treatment:

Drug: BIBR 1048 MS

BIBR 1048 MS Placebo (Japanese)

Placebo Comparator group

Description:

Japanese subjects will receive placebo of BIBR 1048 MS

Treatment:

Drug: Placebo of BIBR 1048 MS

BIBR 1048 MS (Caucasian)

Experimental group

Description:

Caucasian subjects received an increasing dose (50 mg to 150 mg) of BIBR 1048 MS

Treatment:

Drug: BIBR 1048 MS

BIBR 1048 MS Placebo (Caucasian)

Placebo Comparator group

Description:

Japanese subjects will receive placebo of BIBR 1048 MS

Treatment:

Drug: Placebo of BIBR 1048 MS