A Study to Find Out How YM150 is Absorbed Into and Eliminated From the Body in Healthy Male Subjects

An Open Label Study to Evaluate the Pharmacokinetics of YM150 After a Single Oral Dose of C14-labeled YM150 in Healthy Male Subjects

The study aims to observe how YM150 was absorbed, distributed and excreted after dosing with a radio labeled drinking solution.

Study Overview

• Status: Completed
• Conditions: Healthy Male Subjects; Pharmacokinetics
• Intervention / Treatment: Drug: YM150

Detailed Description

Healthy male subjects are admitted on Day 0. Subjects receive a single oral dose of 14C-labeled YM150 in the morning of Day 1 and remain in the unit for 7 days (6 nights). Blood, plasma, urine and feces samples are collected until 120 hrs after dosing for analysis of 14C-labeled radioactivity, YM150, YM-222714 and other metabolites. Expired air is collected as well for assessment of 14C-radioactivity.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Zuidlaren, Netherlands, 9471 GP
    • PRA International EDS NL

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Body weight between 60 and 100 kg and Body Mass Index between 18 and 30 kg/m2

Exclusion Criteria:

• Known or suspected hypersensitivity to YM150 or any of the constituents of the formulations used
• History of and/or any sign or symptom indicating current abnormal hemostasis or blood dyscrasia, including but not limited to neutropenia, thrombocytopenia, thrombocytopathy, thromboasthenia, hemophilia, Von Willebrand's disease, and vascular purpura, bleeding gums or frequent nose bleeding
• Family history of congenital vascular malformation (e.g. Marfan's Syndrome) and/or bleeding disorder (e.g. hemophilia, Von Willebrand's disease, Christmas disease)
• History of peptic ulcer or of any other organic lesion susceptible to bleeding
• Prothrombin time (PT) or Activated partial thromboplastin time (aPTT) at the screening visit outside the normal range
• Any surgical intervention (including tooth extraction) or trauma within the last 3 months preceding the start of the study
• Any clinically significant history of asthma, eczema, any other clinically significant allergic condition or previous severe hypersensitivity to any other drug
• Any clinically significant upper gastro-intestinal symptoms likely to interfere with the absorption of the drug
• History or presence of any cardiovascular disease or disorder
• History of a clinically significant ECG abnormality
• Any clinically relevant history of other disease or disorder - gastrointestinal, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic
• Any clinically significant abnormality following the Investigator's review of the pre-study physical examination, ECG, and clinical laboratory tests
• Abnormal heart rate and blood pressure measurements at the screening visit as follows: heart rate <40 or >90 bpm; mean systolic blood pressure <95 or >160 mmHg; mean diastolic blood pressure <40 or >95 mmHg (blood pressure measurements taken in triplicate after subject has been resting in supine position for 5 min)
• Regular use of any prescribed or OTC drugs (including vitamins and herbal remedies) in the 4 weeks prior to admission to the clinical unit OR any use of such drugs in the 2 weeks prior to admission to the clinical unit
• History of drug abuse at any time, OR any use of drugs of abuse within 3 months prior to admission to the clinical unit
• Participation in any clinical study within 3 months, or participation in more than 3 clinical studies within 12 months, prior to the expected date of enrolment into the study
• History of drinking more than 21 units of alcohol per week (1 unit = 270 ml of beer or 40 ml of spirits or 125 ml of wine) within 3 months prior to admission to the clinical unit
• History of smoking more than 10 cigarettes (or equivalent amount of tobacco) per day within 3 months prior to admission to the clinical unit
• Subject, who is anti-HAV (IgM), anti-HCV, HBsAg or HIV-1 or -2 positive
• Donation of blood (>400 ml) or blood products within 3 months prior to admission to the clinical unit or plasmapheresis within 4 weeks prior to admission to the clinical unit
• Exposure to radiation for diagnostic reasons (except dental X-rays and plain X-rays of thorax and bony skeleton (excluding spinal column)), during work or during participation in a clinical study in the previous year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment arm 1	Drug: YM150; 14C-labeled YM150, oral solution; Other Names: darexaban

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of 14C-labeled YM150 assessed by whole blood, plasma, urine, feces and expired air concentrations	AUCinf (Amount excreted in urine extrapolated until infinity), AUClast (Amount excreted in urine until last sample), Cmax (Maximum concentration), tmax (Time to attain maximum concentration), tlag (Absorption lag time) and t1/2 (Apparent terminal elimination half-life). Excretion rate and cumulative excretion of radioactivity in urine, feces and expired air.	Day 1 - Day 6
Pharmacokinetics of YM150 and metabolites assessed by plasma and urine concentrations	- AUCinf, AUClast, Cmax, tmax, tlag and t1/2. In urine - amount excreted in urine, CLR (Renal clearance) and % of dose excreted.	Day 1 - Day 6

Secondary Outcome Measures

Outcome Measure	Time Frame
Identification of the metabolic profile of YM150 in human plasma, urine and feces	0 - 2 hours Day 1
Monitoring of safety and tolerability through assessment of vital signs, Electrocardiogram (ECG), clinical safety laboratory and adverse events	Day 1 - 14

Collaborators and Investigators

• Sponsor: Astellas Pharma Europe B.V.

Publications and helpful links

Helpful Links

• Link to Results on JAPIC

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: July 10, 2012
• First Submitted That Met QC Criteria: August 1, 2012
• First Posted (Estimate): August 6, 2012

Study Record Updates

• Last Update Posted (Estimate): June 26, 2013
• Last Update Submitted That Met QC Criteria: June 24, 2013
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Phase 1; 14C-labeled
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Darexaban
• Other Study ID Numbers: 150-CL-015; 2006-001968-22 (EudraCT Number)