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A Study to Investigate the Effect of YM150 on the Plasma Concentration of Digoxin in Healthy Subjects

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ClinicalTrials.gov Identifier: NCT01514812
Recruitment Status : Completed
First Posted : January 23, 2012
Last Update Posted : January 24, 2012
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc

Brief Summary:
This study is to evaluate the effect of YM150 on the plasma concentration of digoxin in healthy subjects.

Condition or disease Intervention/treatment Phase
Healthy Pharmacokinetic of Digoxin Drug: YM150 Drug: placebo Drug: digoxin Phase 1

Detailed Description:

The study will be of a double blind, randomized, two period crossover design. Two treatments, digoxin in combination with YM150, and digoxin in combination with placebo, will be evaluated. Each subject will receive both treatments in random order. Placebo will be used to maintain the blind. Males and females will be equally divided over the treatment orders.

Subjects will be dosed with digoxin and either YM150 or placebo for 8 days to reach steady state. In the second period the subjects will receive digoxin and the alternate treatment. There will be a washout period of at least 10 days between the consecutive treatments. In both study periods the subjects will be admitted the day prior to study drug administration (Day 0). The subjects will be discharged on Day 10. Approximately one week after the last discharge, the subjects will return to the unit for a post study visit.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Official Title: A Double Blind, Randomized, Two Period Crossover Study To Determine The Effect of Multiple Doses of 120 MG Modified Release Formulation of YM150 on the Steady State Pharmacokinetics of Digoxin in Healthy Subjects
Study Start Date : February 2006
Actual Primary Completion Date : April 2006
Actual Study Completion Date : April 2006

Resource links provided by the National Library of Medicine

Drug Information available for: Digoxin

Arm Intervention/treatment
Experimental: YM150-placebo sequence group
YM150+digoxin; Washout; Placebo+digoxin
Drug: YM150
oral - modified release formulation of YM150
Other Name: darexaban

Drug: placebo
oral

Drug: digoxin
oral

Experimental: placebo-YM150 sequence group
Placebo+digoxin; Washout; YM150+digoxin
Drug: YM150
oral - modified release formulation of YM150
Other Name: darexaban

Drug: placebo
oral

Drug: digoxin
oral




Primary Outcome Measures :
  1. Cmax of digoxin assessed by its plasma concentration change [ Time Frame: for 24 hour after the last dose of each period ]
  2. AUC of digoxin assessed by its plasma concentration change [ Time Frame: for 24 hour after the last dose of each period ]

Secondary Outcome Measures :
  1. Changes in the blood coaggregation indexes such as PT(INR), aPTT and FXa [ Time Frame: before dosing and 5hr after dosing on days 4 and 8 and 24h and 48h after the last dose ]
  2. Safety assessed by the incidence of adverse events, vital signs, 12-lead ECG and labo-tests [ Time Frame: for 10 days after dosing ]


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy, as judged by the investigator or sub-investigator based on the results of physical examinations and all tests
  • Body weight: male: ≥60 kg, <100 kg; female: ≥45.0 kg, <80.0 kg
  • BMI (at screening): ≥18.0, <30.0

Exclusion Criteria:

  • Female subjects of child-bearing potential, not practicing adequate methods to prevent pregnancies, like abstinence or double barrier methods
  • Known or suspected hypersensitivity / allergy to FXa inhibitors, digoxin, or heart glycosides in general or 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)
  • PT or aPTT at the screening visit outside the normal range
  • History of peptic ulcer or of any other organic lesion susceptible to bleed
  • Any surgical intervention (including tooth extraction) or trauma within the last 3 months preceding the initiation of the study
  • Any clinically significant history of upper gastrointestinal symptoms (such as nausea, vomiting, abdominal discomfort or upset, or heartburn) in the 4 weeks prior to admission to the Research Unit
  • Any clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic
  • Any of the liver function tests (ALAT, ASAT, LDH and γ-GT) above the upper limit of normal range (ULN)
  • Any clinically significant abnormality following the investigator's review of the prestudy physical examination, ECG and clinical laboratory tests
  • Abnormal pulse rate and blood pressure measurements at the pre-study visit as follows: Pulse rate <40 or >90 bpm; systolic blood pressure <95 or >160 mmHg; diastolic blood pressure <40 or >95 mmHg (measurements taken after subject has been resting in supine position for 5 min)
  • Regular use of any prescribed or OTC (over-the-counter) drugs (including natural and herbal remedies and especially those with P-gp inhibiting activity, like St. John's worth) in the four weeks prior to admission to the Research Unit OR any use of such drugs (including natural and herbal remedies) as well as vitamins in the two weeks prior to admission to the Research Unit
  • Donation of blood or blood products within 3 months prior to admission to the Research Unit

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01514812


Locations
France
Paris, France
Sponsors and Collaborators
Astellas Pharma Inc
Investigators
Study Chair: Use Central Contact Astellas Pharma Inc

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Astellas Pharma Inc
ClinicalTrials.gov Identifier: NCT01514812     History of Changes
Other Study ID Numbers: 150-CL-007
2004-004930-15 ( EudraCT Number )
First Posted: January 23, 2012    Key Record Dates
Last Update Posted: January 24, 2012
Last Verified: January 2012

Keywords provided by Astellas Pharma Inc:
YM150
digoxin
drug-drug interaction
Plasma concentration
darexaban
Pharmacokinetics of digoxin

Additional relevant MeSH terms:
Digoxin
Darexaban
Anti-Arrhythmia Agents
Cardiotonic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Anticoagulants