{
  "FullStudy":{
    "Rank":217943,
    "Study":{
      "ProtocolSection":{
        "IdentificationModule":{
          "NCTId":"NCT01514812",
          "OrgStudyIdInfo":{
            "OrgStudyId":"150-CL-007"
          },
          "SecondaryIdInfoList":{
            "SecondaryIdInfo":[
              {
                "SecondaryId":"2004-004930-15",
                "SecondaryIdType":"EudraCT Number"
              }
            ]
          },
          "Organization":{
            "OrgFullName":"Astellas Pharma Inc",
            "OrgClass":"INDUSTRY"
          },
          "BriefTitle":"A Study to Investigate the Effect of YM150 on the Plasma Concentration of Digoxin in Healthy Subjects",
          "OfficialTitle":"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"
        },
        "StatusModule":{
          "StatusVerifiedDate":"January 2012",
          "OverallStatus":"Completed",
          "ExpandedAccessInfo":{
            "HasExpandedAccess":"No"
          },
          "StartDateStruct":{
            "StartDate":"February 2006"
          },
          "PrimaryCompletionDateStruct":{
            "PrimaryCompletionDate":"April 2006",
            "PrimaryCompletionDateType":"Actual"
          },
          "CompletionDateStruct":{
            "CompletionDate":"April 2006",
            "CompletionDateType":"Actual"
          },
          "StudyFirstSubmitDate":"January 18, 2012",
          "StudyFirstSubmitQCDate":"January 20, 2012",
          "StudyFirstPostDateStruct":{
            "StudyFirstPostDate":"January 23, 2012",
            "StudyFirstPostDateType":"Estimate"
          },
          "LastUpdateSubmitDate":"January 23, 2012",
          "LastUpdatePostDateStruct":{
            "LastUpdatePostDate":"January 24, 2012",
            "LastUpdatePostDateType":"Estimate"
          }
        },
        "SponsorCollaboratorsModule":{
          "ResponsibleParty":{
            "ResponsiblePartyType":"Sponsor"
          },
          "LeadSponsor":{
            "LeadSponsorName":"Astellas Pharma Inc",
            "LeadSponsorClass":"INDUSTRY"
          }
        },
        "OversightModule":{
          "OversightHasDMC":"No"
        },
        "DescriptionModule":{
          "BriefSummary":"This study is to evaluate the effect of YM150 on the plasma concentration of digoxin in healthy subjects.",
          "DetailedDescription":"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.\n\nSubjects 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."
        },
        "ConditionsModule":{
          "ConditionList":{
            "Condition":[
              "Healthy",
              "Pharmacokinetic of Digoxin"
            ]
          },
          "KeywordList":{
            "Keyword":[
              "YM150",
              "digoxin",
              "drug-drug interaction",
              "Plasma concentration",
              "darexaban",
              "Pharmacokinetics of digoxin"
            ]
          }
        },
        "DesignModule":{
          "StudyType":"Interventional",
          "PhaseList":{
            "Phase":[
              "Phase 1"
            ]
          },
          "DesignInfo":{
            "DesignAllocation":"Randomized",
            "DesignInterventionModel":"Crossover Assignment",
            "DesignMaskingInfo":{
              "DesignMasking":"Quadruple",
              "DesignWhoMaskedList":{
                "DesignWhoMasked":[
                  "Participant",
                  "Care Provider",
                  "Investigator",
                  "Outcomes Assessor"
                ]
              }
            }
          },
          "EnrollmentInfo":{
            "EnrollmentCount":"24",
            "EnrollmentType":"Actual"
          }
        },
        "ArmsInterventionsModule":{
          "ArmGroupList":{
            "ArmGroup":[
              {
                "ArmGroupLabel":"YM150-placebo sequence group",
                "ArmGroupType":"Experimental",
                "ArmGroupDescription":"YM150+digoxin; Washout; Placebo+digoxin",
                "ArmGroupInterventionList":{
                  "ArmGroupInterventionName":[
                    "Drug: YM150",
                    "Drug: placebo",
                    "Drug: digoxin"
                  ]
                }
              },{
                "ArmGroupLabel":"placebo-YM150 sequence group",
                "ArmGroupType":"Experimental",
                "ArmGroupDescription":"Placebo+digoxin; Washout; YM150+digoxin",
                "ArmGroupInterventionList":{
                  "ArmGroupInterventionName":[
                    "Drug: YM150",
                    "Drug: placebo",
                    "Drug: digoxin"
                  ]
                }
              }
            ]
          },
          "InterventionList":{
            "Intervention":[
              {
                "InterventionType":"Drug",
                "InterventionName":"YM150",
                "InterventionDescription":"oral - modified release formulation of YM150",
                "InterventionArmGroupLabelList":{
                  "InterventionArmGroupLabel":[
                    "YM150-placebo sequence group",
                    "placebo-YM150 sequence group"
                  ]
                },
                "InterventionOtherNameList":{
                  "InterventionOtherName":[
                    "darexaban"
                  ]
                }
              },{
                "InterventionType":"Drug",
                "InterventionName":"placebo",
                "InterventionDescription":"oral",
                "InterventionArmGroupLabelList":{
                  "InterventionArmGroupLabel":[
                    "YM150-placebo sequence group",
                    "placebo-YM150 sequence group"
                  ]
                }
              },{
                "InterventionType":"Drug",
                "InterventionName":"digoxin",
                "InterventionDescription":"oral",
                "InterventionArmGroupLabelList":{
                  "InterventionArmGroupLabel":[
                    "YM150-placebo sequence group",
                    "placebo-YM150 sequence group"
                  ]
                }
              }
            ]
          }
        },
        "OutcomesModule":{
          "PrimaryOutcomeList":{
            "PrimaryOutcome":[
              {
                "PrimaryOutcomeMeasure":"Cmax of digoxin assessed by its plasma concentration change",
                "PrimaryOutcomeTimeFrame":"for 24 hour after the last dose of each period"
              },{
                "PrimaryOutcomeMeasure":"AUC of digoxin assessed by its plasma concentration change",
                "PrimaryOutcomeTimeFrame":"for 24 hour after the last dose of each period"
              }
            ]
          },
          "SecondaryOutcomeList":{
            "SecondaryOutcome":[
              {
                "SecondaryOutcomeMeasure":"Changes in the blood coaggregation indexes such as PT(INR), aPTT and FXa",
                "SecondaryOutcomeTimeFrame":"before dosing and 5hr after dosing on days 4 and 8 and 24h and 48h after the last dose"
              },{
                "SecondaryOutcomeMeasure":"Safety assessed by the incidence of adverse events, vital signs, 12-lead ECG and labo-tests",
                "SecondaryOutcomeTimeFrame":"for 10 days after dosing"
              }
            ]
          }
        },
        "EligibilityModule":{
          "EligibilityCriteria":"Inclusion Criteria:\n\nHealthy, as judged by the investigator or sub-investigator based on the results of physical examinations and all tests\nBody weight: male: ≥60 kg, <100 kg; female: ≥45.0 kg, <80.0 kg\nBMI (at screening): ≥18.0, <30.0\n\nExclusion Criteria:\n\nFemale subjects of child-bearing potential, not practicing adequate methods to prevent pregnancies, like abstinence or double barrier methods\nKnown or suspected hypersensitivity / allergy to FXa inhibitors, digoxin, or heart glycosides in general or the constituents of the formulations used\nHistory 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\nFamily history of congenital vascular malformation (e.g. Marfan's Syndrome) and/or bleeding disorder (e.g. hemophilia, Von Willebrand's disease, Christmas disease)\nPT or aPTT at the screening visit outside the normal range\nHistory of peptic ulcer or of any other organic lesion susceptible to bleed\nAny surgical intervention (including tooth extraction) or trauma within the last 3 months preceding the initiation of the study\nAny 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\nAny clinically significant history of any other disease or disorder - gastrointestinal, cardiovascular, respiratory, renal, hepatic, neurological, dermatological, psychiatric or metabolic\nAny of the liver function tests (ALAT, ASAT, LDH and γ-GT) above the upper limit of normal range (ULN)\nAny clinically significant abnormality following the investigator's review of the prestudy physical examination, ECG and clinical laboratory tests\nAbnormal 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)\nRegular 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\nDonation of blood or blood products within 3 months prior to admission to the Research Unit",
          "HealthyVolunteers":"Accepts Healthy Volunteers",
          "Gender":"All",
          "MinimumAge":"18 Years",
          "MaximumAge":"55 Years",
          "StdAgeList":{
            "StdAge":[
              "Adult"
            ]
          }
        },
        "ContactsLocationsModule":{
          "OverallOfficialList":{
            "OverallOfficial":[
              {
                "OverallOfficialName":"Use Central Contact",
                "OverallOfficialAffiliation":"Astellas Pharma Inc",
                "OverallOfficialRole":"Study Chair"
              }
            ]
          },
          "LocationList":{
            "Location":[
              {
                "LocationCity":"Paris",
                "LocationCountry":"France"
              }
            ]
          }
        },
        "ReferencesModule":{
          "ReferenceList":{
            "Reference":[
              {
                "ReferencePMID":"23754514",
                "ReferenceType":"derived",
                "ReferenceCitation":"Kadokura T, Groenendaal D, Heeringa M, Mol R, Verheggen F, Garcia-Hernandez A, Onkels H. Darexaban (YM150), an oral direct factor Xa inhibitor, has no effect on the pharmacokinetics of digoxin. Eur J Drug Metab Pharmacokinet. 2014 Mar;39(1):1-9. doi: 10.1007/s13318-013-0141-1. Epub 2013 Jun 11."
              }
            ]
          }
        }
      },
      "DerivedSection":{
        "MiscInfoModule":{
          "VersionHolder":"April 22, 2020"
        },
        "InterventionBrowseModule":{
          "InterventionMeshList":{
            "InterventionMesh":[
              {
                "InterventionMeshId":"D000004077",
                "InterventionMeshTerm":"Digoxin"
              },{
                "InterventionMeshId":"C000569750",
                "InterventionMeshTerm":"Darexaban"
              }
            ]
          },
          "InterventionAncestorList":{
            "InterventionAncestor":[
              {
                "InterventionAncestorId":"D000000889",
                "InterventionAncestorTerm":"Anti-Arrhythmia Agents"
              },{
                "InterventionAncestorId":"D000002316",
                "InterventionAncestorTerm":"Cardiotonic Agents"
              },{
                "InterventionAncestorId":"D000004791",
                "InterventionAncestorTerm":"Enzyme Inhibitors"
              },{
                "InterventionAncestorId":"D000045504",
                "InterventionAncestorTerm":"Molecular Mechanisms of Pharmacological Action"
              },{
                "InterventionAncestorId":"D000020011",
                "InterventionAncestorTerm":"Protective Agents"
              },{
                "InterventionAncestorId":"D000045505",
                "InterventionAncestorTerm":"Physiological Effects of Drugs"
              },{
                "InterventionAncestorId":"D000065427",
                "InterventionAncestorTerm":"Factor Xa Inhibitors"
              },{
                "InterventionAncestorId":"D000000991",
                "InterventionAncestorTerm":"Antithrombins"
              },{
                "InterventionAncestorId":"D000015842",
                "InterventionAncestorTerm":"Serine Proteinase Inhibitors"
              },{
                "InterventionAncestorId":"D000011480",
                "InterventionAncestorTerm":"Protease Inhibitors"
              },{
                "InterventionAncestorId":"D000000925",
                "InterventionAncestorTerm":"Anticoagulants"
              }
            ]
          },
          "InterventionBrowseLeafList":{
            "InterventionBrowseLeaf":[
              {
                "InterventionBrowseLeafId":"M5848",
                "InterventionBrowseLeafName":"Digoxin",
                "InterventionBrowseLeafAsFound":"Digoxin",
                "InterventionBrowseLeafRelevance":"high"
              },{
                "InterventionBrowseLeafId":"M234983",
                "InterventionBrowseLeafName":"Darexaban",
                "InterventionBrowseLeafAsFound":"Darexaban",
                "InterventionBrowseLeafRelevance":"high"
              },{
                "InterventionBrowseLeafId":"M2794",
                "InterventionBrowseLeafName":"Anti-Arrhythmia Agents",
                "InterventionBrowseLeafRelevance":"low"
              },{
                "InterventionBrowseLeafId":"M4154",
                "InterventionBrowseLeafName":"Cardiotonic Agents",
                "InterventionBrowseLeafRelevance":"low"
              },{
                "InterventionBrowseLeafId":"M20453",
                "InterventionBrowseLeafName":"Protective Agents",
                "InterventionBrowseLeafRelevance":"low"
              },{
                "InterventionBrowseLeafId":"M29100",
                "InterventionBrowseLeafName":"Factor Xa Inhibitors",
                "InterventionBrowseLeafRelevance":"low"
              },{
                "InterventionBrowseLeafId":"M2888",
                "InterventionBrowseLeafName":"Antithrombins",
                "InterventionBrowseLeafRelevance":"low"
              },{
                "InterventionBrowseLeafId":"M2887",
                "InterventionBrowseLeafName":"Antithrombin III",
                "InterventionBrowseLeafRelevance":"low"
              },{
                "InterventionBrowseLeafId":"M12926",
                "InterventionBrowseLeafName":"Protease Inhibitors",
                "InterventionBrowseLeafRelevance":"low"
              },{
                "InterventionBrowseLeafId":"M16974",
                "InterventionBrowseLeafName":"Serine Proteinase Inhibitors",
                "InterventionBrowseLeafRelevance":"low"
              },{
                "InterventionBrowseLeafId":"M18192",
                "InterventionBrowseLeafName":"HIV Protease Inhibitors",
                "InterventionBrowseLeafRelevance":"low"
              },{
                "InterventionBrowseLeafId":"M2825",
                "InterventionBrowseLeafName":"Anticoagulants",
                "InterventionBrowseLeafRelevance":"low"
              },{
                "InterventionBrowseLeafId":"T18",
                "InterventionBrowseLeafName":"Serine",
                "InterventionBrowseLeafRelevance":"low"
              }
            ]
          },
          "InterventionBrowseBranchList":{
            "InterventionBrowseBranch":[
              {
                "InterventionBrowseBranchAbbrev":"AnArAg",
                "InterventionBrowseBranchName":"Anti-Arrhythmia Agents"
              },{
                "InterventionBrowseBranchAbbrev":"CaAg",
                "InterventionBrowseBranchName":"Cardiotonic Agents"
              },{
                "InterventionBrowseBranchAbbrev":"All",
                "InterventionBrowseBranchName":"All Drugs and Chemicals"
              },{
                "InterventionBrowseBranchAbbrev":"AnCoag",
                "InterventionBrowseBranchName":"Anticoagulants"
              },{
                "InterventionBrowseBranchAbbrev":"Infe",
                "InterventionBrowseBranchName":"Anti-Infective Agents"
              },{
                "InterventionBrowseBranchAbbrev":"AA",
                "InterventionBrowseBranchName":"Amino Acids"
              }
            ]
          }
        }
      }
    }
  }
}