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

NCT02170844 | Completed Phase 1

• 1 other identifier: 1160.28
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (9)

• Change from baseline in blood pressure (BP)

  At screening (day -14 to -3), at day -1, pre-dose, 2, 8, 24, 48 h after administration and on visit 5 (day 10 to day 14 after administration)

• Change from baseline in pulse rate (PR)

  At screening (day -14 to -3), at day -1, pre-dose, 2, 8, 24, 48 h after administration and on visit 5 (day 10 to day 14 after administration)

• Change from baseline in respiratory rate

  At screening (day -14 to -3), at day -1, pre-dose, 2, 8, 24, 48 h after administration and on visit 5 (day 10 to day 14 after administration)

• Change from baseline in tympanic body temperature

  At screening (day -14 to -3), at day -1, pre-dose, 2, 8, 24, 48 h after administration and on visit 5 (day 10 to day 14 after administration)

• Change from baseline in 12-Lead electrocardiogram (ECG)

  At screening (day -14 to -3), at day -1, pre-dose, 2, 48 h after administration and on visit 5 (day 10 to day 14 after administration)

• Change from baseline in haematology

  At screening (day -14 to -3), at day -1 (pre-dose), 48 h after administration and on visit 5 (day 10 to day 14 after administration)

• Change from baseline in blood chemistry

  At screening (day -14 to -3), at day -1 (pre-dose), 48 h after administration and on visit 5 (day 10 to day 14 after administration)

• Change from baseline in urinalysis

  At screening (day -14 to -3), at day -1 (pre-dose), 4, 8, 12, 24, 36, 48 h after administration and on visit 5 (day 10 to day 14 after administration)

• Occurence of adverse events

  Up to visit 5 (day 10 - 14)

Secondary Outcomes (16)

• Cmax (maximum concentration of the analyte in plasma)

  pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration

• tmax (time from dosing to maximum concentration)

  pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration

• AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)

  pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration

• AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable point)

  pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration

• λz (terminal rate constant in plasma)

  pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration

Study Arms (4)

BIBR 1048 MS (Japanese)

EXPERIMENTAL

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

Drug: BIBR 1048 MS

BIBR 1048 MS Placebo (Japanese)

PLACEBO COMPARATOR

Japanese subjects will receive placebo of BIBR 1048 MS

Drug: Placebo of BIBR 1048 MS

BIBR 1048 MS (Caucasian)

EXPERIMENTAL

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

Drug: BIBR 1048 MS

BIBR 1048 MS Placebo (Caucasian)

PLACEBO COMPARATOR

Japanese subjects will receive placebo of BIBR 1048 MS

Drug: Placebo of BIBR 1048 MS

Interventions

BIBR 1048 MS DRUG

BIBR 1048 MS (Caucasian); BIBR 1048 MS (Japanese)

Placebo of BIBR 1048 MS DRUG

BIBR 1048 MS Placebo (Caucasian); BIBR 1048 MS Placebo (Japanese)

Eligibility Criteria

• Age: 20 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• No finding deviating from normal and of clinical relevance
• No evidence of a clinically relevant concomitant disease
• Age ≥20 and Age ≤45 years
• BMI ≥18 and BMI ≤25 kg/m2 (Body Mass Index)
• 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.
• Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation.

You may not qualify if:

• Current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• 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
• Current diseases of the central nervous system (such as epilepsy), or psychiatric disorders or neurological disorders
• History of clinically significant orthostatic hypotension, clinically significant current or past fainting spells or blackouts.
• 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)
• concussions (head trauma resulting in injuring to brain) with or without loss of consciousness
• 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
• 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.
• 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.
• Participation in another trial with an investigational drug within three months prior to administration or during the trial
• Smoker (\> 10 cigarettes/day or \> 3 cigars/day or \> 3 pipes/day)

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2014
• First Posted: June 23, 2014
• Study Start: June 1, 2004
• Primary Completion: August 1, 2004
• Last Updated: August 31, 2018

Record last verified: 2018-08