Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of BI 11634 Solution in Healthy Male Volunteers

Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Rising Oral Doses of 5, 10, 25, 50, 100, 200 and 400 mg BI 11634 Solution Administered to Healthy Male Volunteers. Randomised, Double-blind, Placebo Controlled at Each Dose Level. Intra-individual Comparison of Solution to an Immediate Release Tablet Formulation at One Dose Level (50 mg)

First evaluation of safety, tolerability, pharmacokinetics and the pharmacodynamic effect of BI 11634 on coagulation parameters

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: BI 11634 tablet; Drug: BI 11634 drinking solution

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy males according to the following criteria:

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

• Age ≥18 and ≤50 years
• Haemoglobin within the normal ranges
• Body Mass Index (BMI) ≥18.5 and BMI ≤29.9 kg/m2
• 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:

• Relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Relevant surgery of gastrointestinal tract
• History of any bleeding disorder or acute blood coagulation defect, for the subject itself or any person of his family as far as known
• History of gastric ulcera and cholecystectomy
• Occult blood in feces
• Relevant diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
• History of relevant orthostatic hypotension, fainting spells or blackouts
• Relevant chronic or acute infections
• History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
• Intake of drugs with a long half-life (>24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial
• Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial
• Use of acetylsalicylic acid or any other non-steroidal anti-inflammatory drugs (NSAID) within 2 weeks of study start until the end of study
• Participation in another trial with an investigational drug within two months prior to administration or during the trial
• Alcohol abuse (more than 40 g/day)
• Drug abuse
• Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
• Excessive physical activities (within one week prior to administration or during the trial)
• Any laboratory value outside the reference range that is of clinical relevance
• Vulnerable subjects (e.g. persons kept in detention)
• The subject is not able to understand and comply with protocol requirements, instructions and protocol-stated restrictions
• Subjects with a history within the past 2 weeks of closed head or torso trauma or deceleration injury such as an automobile accident or fall from a significant height

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: BI 11634 drinking solution; single rising dose	Drug: BI 11634 drinking solution
Experimental: BI 11634 tablet	Drug: BI 11634 tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of subjects with adverse events	up to 10 days after drug administration
Number of subjects with clinically significant findings in vital signs (blood pressure, pulse rate)	up to 10 days after drug administration
Number of subjects with clinically significant findings in ECG	up to 10 days after drug administration
Assessment of tolerability by investigator on a 4-point scale	up to 10 days after drug administration
Number of subjects with clinically significant findings laboratory tests	up to 10 days after drug administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent inhibition of thrombin generation by BI 11634		up to 24 hours after drug administration
Percent peak inhibition of thrombin generation		up to 24 hours after drug administration
Time to maximum inhibition of thrombin generation BI 11634		up to 24 hours after drug administration
Percent prolongation of lag time		up to 24 hours after drug administration
Area under the inhibition of the endogenous thrombin generation-time curve		up to 24 hours after drug administration
Cmax (maximum measured concentration of the analyte in plasma)		up to 72 hours after drug administration
t1/2 (terminal half-life of the analyte in plasma)		up to 72 hours after drug administration
MRTpo (mean residence time of the analyte in the body after oral administration)		up to 72 hours after drug administration
Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)		up to 72 hours after drug administration
tmax (time from dosing to maximum measured concentration)		up to 72 hours after drug administration
λz (terminal rate constant in plasma)		up to 72 hours after drug administration
Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2)		up to 48 hours after drug administration
fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2)		up to 48 hours after drug administration
CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2)		up to 48 hours after drug administration
AUC0-inf (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity)		up to 72 hours after drug administration
AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 up to the last quantifiable data point)		up to 72 hours after drug administration
CL/F (apparent clearance of the analyte in plasma after extravascular administration)		up to 72 hours after drug administration
Activated partial thromboplastin time (aPTT) ratios between groups		up to 72 hours after drug administration
Maximum aPTT prolongation	compared between groups	up to 72 hours after drug administration
Maximum international normalized ratio (INR)	compared between groups	up to 72 hours after drug administration
% inhibition of endogenous Factor Xa	by Russel's Viper Venom test (RVV)	up to 72 hours after drug administration
Maximum prolongation of blood coagulation time	by HepTest® (Haemachem Inc.) and COAMATIC® Heparin test (Chromogenix)	up to 72 hours after drug administration

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): March 1, 2007

Study Registration Dates

• First Submitted: August 12, 2014
• First Submitted That Met QC Criteria: August 12, 2014
• First Posted (Estimate): August 13, 2014

Study Record Updates

• Last Update Posted (Actual): August 31, 2018
• Last Update Submitted That Met QC Criteria: August 29, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Other Study ID Numbers: 1234.1