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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc
ClinicalTrials.gov Identifier:
NCT01514812
First received: January 18, 2012
Last updated: January 23, 2012
Last verified: January 2012
  Purpose

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


Condition Intervention Phase
Healthy
Pharmacokinetic of Digoxin
Drug: YM150
Drug: placebo
Drug: digoxin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc:

Primary Outcome Measures:
  • Cmax of digoxin assessed by its plasma concentration change [ Time Frame: for 24 hour after the last dose of each period ] [ Designated as safety issue: No ]
  • AUC of digoxin assessed by its plasma concentration change [ Time Frame: for 24 hour after the last dose of each period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Safety assessed by the incidence of adverse events, vital signs, 12-lead ECG and labo-tests [ Time Frame: for 10 days after dosing ] [ Designated as safety issue: No ]

Enrollment: 24
Study Start Date: February 2006
Study Completion Date: April 2006
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01514812

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

No publications provided by Astellas Pharma Inc

Additional 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
Study First Received: January 18, 2012
Last Updated: January 23, 2012
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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

Additional relevant MeSH terms:
Digoxin
Anti-Arrhythmia Agents
Cardiotonic Agents
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014