{ "FullStudy":{ "Rank":217744, "Study":{ "ProtocolSection":{ "IdentificationModule":{ "NCTId":"NCT01517399", "OrgStudyIdInfo":{ "OrgStudyId":"ARQ197-A-U158" }, "Organization":{ "OrgFullName":"Daiichi Sankyo, Inc.", "OrgClass":"INDUSTRY" }, "BriefTitle":"Drug-drug Interaction Study of Tivantinib (ARQ 197) With Omeprazole, S-warfarin, Caffeine, Midazolam, and Digoxin in Cancer Subjects", "OfficialTitle":"A Phase 1, Open-Label, Single-Sequence Crossover Study Assessing the Effect of Tivantinib (ARQ 197) on the Pharmacokinetics of Omeprazole/S-Warfarin/Caffeine/Midazolam and Digoxin in Cancer Subjects" }, "StatusModule":{ "StatusVerifiedDate":"February 2018", "OverallStatus":"Completed", "ExpandedAccessInfo":{ "HasExpandedAccess":"No" }, "StartDateStruct":{ "StartDate":"December 2011" }, "PrimaryCompletionDateStruct":{ "PrimaryCompletionDate":"August 2013", "PrimaryCompletionDateType":"Actual" }, "CompletionDateStruct":{ "CompletionDate":"September 2013", "CompletionDateType":"Actual" }, "StudyFirstSubmitDate":"January 4, 2012", "StudyFirstSubmitQCDate":"January 20, 2012", "StudyFirstPostDateStruct":{ "StudyFirstPostDate":"January 25, 2012", "StudyFirstPostDateType":"Estimate" }, "LastUpdateSubmitDate":"February 8, 2019", "LastUpdatePostDateStruct":{ "LastUpdatePostDate":"February 12, 2019", "LastUpdatePostDateType":"Actual" } }, "SponsorCollaboratorsModule":{ "ResponsibleParty":{ "ResponsiblePartyType":"Sponsor" }, "LeadSponsor":{ "LeadSponsorName":"Daiichi Sankyo, Inc.", "LeadSponsorClass":"INDUSTRY" }, "CollaboratorList":{ "Collaborator":[ { "CollaboratorName":"Medpace, Inc.", "CollaboratorClass":"INDUSTRY" } ] } }, "OversightModule":{ "OversightHasDMC":"No" }, "DescriptionModule":{ "BriefSummary":"The purpose of this study is to determine the effects of tivantinib on the pharmacokinetics of omeprazole, s-warfarin, caffein, midazolam, or digoxin in patients with cancer.", "DetailedDescription":"Nonclinical studies have indicated that tivantinib (parent molecule) has the potential to inhibit CYP3A4 ([I]/Ki=0.15, midazolam as substrate), CYP2C19 ([I]/Ki=0.98), CYP2C9 ([I]/Ki=0.44), and CYP1A ([I]/Ki=0.37), and the efflux transporter P glycoprotein (P-gp) (I2/IC50=82) at the clinical concentrations being studied in the Phase 3 development program. In addition, tivantinib has major circulating plasma metabolite(s) which also have been shown in nonclinical studies to exhibit similar CYP inhibition potential. The results of this study will evaluate the potential of tivantinib to influence the pharmacokinetics of CYP3A4/CYP2C19/CYP2C9/CYP1A and/or P-gp substrates, and help to provide the guidance to clinicians on co-administration of tivantinib with drugs metabolized by CYP3A4/CYP2C19/CYP2C9/ CYP1A and/or transported by P-gp." }, "ConditionsModule":{ "ConditionList":{ "Condition":[ "Solid Tumors" ] }, "KeywordList":{ "Keyword":[ "Oncology", "pharmacokinetics", "PK interaction in advanced solid tumors with our drug and other drugs" ] } }, "DesignModule":{ "StudyType":"Interventional", "PhaseList":{ "Phase":[ "Phase 1" ] }, "DesignInfo":{ "DesignInterventionModel":"Sequential Assignment", "DesignPrimaryPurpose":"Other", "DesignMaskingInfo":{ "DesignMasking":"None (Open Label)" } }, "EnrollmentInfo":{ "EnrollmentCount":"28", "EnrollmentType":"Actual" } }, "ArmsInterventionsModule":{ "ArmGroupList":{ "ArmGroup":[ { "ArmGroupLabel":"Test drug administration", "ArmGroupType":"Other", "ArmGroupDescription":"All drugs except vitamin K will be administered as a single dose once by itself as a reference treatment and once with tivantinib", "ArmGroupInterventionList":{ "ArmGroupInterventionName":[ "Drug: tivantinib", "Drug: omeprazole", "Drug: s-warfarin", "Drug: caffeine", "Dietary Supplement: vitamin K", "Drug: digoxin", "Drug: midazolam" ] } } ] }, "InterventionList":{ "Intervention":[ { "InterventionType":"Drug", "InterventionName":"tivantinib", "InterventionDescription":"three oral 120 mg tablets administered twice a day", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Test drug administration" ] }, "InterventionOtherNameList":{ "InterventionOtherName":[ "ARQ 197" ] } },{ "InterventionType":"Drug", "InterventionName":"omeprazole", "InterventionDescription":"One 40 mg oral capsule once alone and once again with tivantinib", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Test drug administration" ] } },{ "InterventionType":"Drug", "InterventionName":"s-warfarin", "InterventionDescription":"One 10 mg oral tablet once alone and once again with tivantinib", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Test drug administration" ] } },{ "InterventionType":"Drug", "InterventionName":"caffeine", "InterventionDescription":"One 200 mg oral tablet once alone and once again with tivantinib", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Test drug administration" ] } },{ "InterventionType":"Dietary Supplement", "InterventionName":"vitamin K", "InterventionDescription":"One oral 5 mg tablet on multiple days when and around warfarin administration", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Test drug administration" ] } },{ "InterventionType":"Drug", "InterventionName":"digoxin", "InterventionDescription":"One oral 0.25 mg tablet once alone and once again with tivantinib", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Test drug administration" ] } },{ "InterventionType":"Drug", "InterventionName":"midazolam", "InterventionDescription":"Intravenous 1.5 mg dose once alone and once again with tivantinib", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Test drug administration" ] } } ] } }, "OutcomesModule":{ "PrimaryOutcomeList":{ "PrimaryOutcome":[ { "PrimaryOutcomeMeasure":"Area under the plasma concentration versus time curve (AUC) for S-Warfarin, Caffeine, Midazolam and Digoxin", "PrimaryOutcomeDescription":"Parameters of S-warfarin/caffeine/midazolam and digoxin (area under the concentration-time curve from time 0 to the last quantifiable concentration [AUC last] and area under the curve from time of dosing extrapolated to infinity [AUC 0-inf]) when warfarin/caffeine/midazolam and digoxin are administered alone or in combination with tivantinib", "PrimaryOutcomeTimeFrame":"Pharmacokinetic sampling will be done on days 1, 4, 6, 10, 11, 14, 16 (designated as days -5, -2, 1, 5, 6, 9, 11 in the study protocol)" },{ "PrimaryOutcomeMeasure":"Area under the plasma concentration versus time curve (AUC) for Omeprazole", "PrimaryOutcomeDescription":"The ratios of omeprazole exposures vs. 5-hydroxyomeprazole exposures in terms of AUC last and AUC 0-inf when omeprazole is administered alone or in combination with tivantinib.", "PrimaryOutcomeTimeFrame":"Pharmacokinetic sampling will be done on days 1, 4, 6, 10, 11, 14, 16 (designated as days -5, -2, 1, 5, 6, 9, 11 in the study protocol)" } ] }, "SecondaryOutcomeList":{ "SecondaryOutcome":[ { "SecondaryOutcomeMeasure":"Maximum observed concentration in plasma [Cmax] - Omeprazole, S-warfarin, Caffeine, Midazolam, Digoxin and the metabolite 5-hydroxyomeprazole", "SecondaryOutcomeDescription":"Maximum observed concentration in plasma [Cmax] when omeprazole, warfarin, caffeine, midazolam and digoxin are administered alone or in combination with tivantinib.", "SecondaryOutcomeTimeFrame":"Pharmacokinetic sampling will be done on days 1, 4, 6, 10, 11, 14, 16 (designated as days -5, -2, 1, 5, 6, 9, 11 in the study protocol)" },{ "SecondaryOutcomeMeasure":"Time to Maximum Plasma Concentration (Tmax) - Omeprazole, S-warfarin, Caffeine, Midazolam, Digoxin and the metabolite 5-hydroxyomeprazole", "SecondaryOutcomeDescription":"Maximum observed concentration in plasma [Tmax] when omeprazole, warfarin, caffeine, midazolam and digoxin are administered alone or in combination with tivantinib.", "SecondaryOutcomeTimeFrame":"Pharmacokinetic sampling will be done on days 1, 4, 6, 10, 11, 14, 16 (designated as days -5, -2, 1, 5, 6, 9, 11 in the study protocol)" },{ "SecondaryOutcomeMeasure":"Apparent oral clearance [CL/F] - Omeprazole, S-warfarin, Caffeine, Midazolam, Digoxin and the metabolite 5-hydroxyomeprazole", "SecondaryOutcomeDescription":"Apparent oral clearance [CL/F] when omeprazole, warfarin, caffeine, midazolam and digoxin are administered alone or in combination with tivantinib.", "SecondaryOutcomeTimeFrame":"Pharmacokinetic sampling will be done on days 1, 4, 6, 10, 11, 14, 16 (designated as days -5, -2, 1, 5, 6, 9, 11 in the study protocol)" },{ "SecondaryOutcomeMeasure":"Apparent volume of distribution [V/F] - Omeprazole, S-warfarin, Caffeine, Midazolam, Digoxin and the metabolite 5-hydroxyomeprazole", "SecondaryOutcomeDescription":"Apparent volume of distribution [V/F] when omeprazole, warfarin, caffeine, midazolam and digoxin are administered alone or in combination with tivantinib.", "SecondaryOutcomeTimeFrame":"Pharmacokinetic sampling will be done on days 1, 4, 6, 10, 11, 14, 16 (designated as days -5, -2, 1, 5, 6, 9, 11 in the study protocol)" },{ "SecondaryOutcomeMeasure":"Maximum observed concentration in plasma [Cmax] for Tivantinib and its major metabolites, HPM4, HPM5, HPM6, and HPM8", "SecondaryOutcomeTimeFrame":"Pharmacokinetic sampling will be done on Days 6, 10, and 16 (designated as days 1, 5, and 11 in the study protocol)" },{ "SecondaryOutcomeMeasure":"Time to Maximum Plasma Concentration (Tmax) for Tivantinib and its major metabolites, HPM4, HPM5, HPM6, and HPM8", "SecondaryOutcomeTimeFrame":"Pharmacokinetic sampling will be done on Days 6, 10, and 16 (designated as days 1, 5, and 11 in the study protocol)" },{ "SecondaryOutcomeMeasure":"Apparent oral clearance [CL/F] for Tivantinib and its major metabolites, HPM4, HPM5, HPM6, and HPM8", "SecondaryOutcomeTimeFrame":"Pharmacokinetic sampling will be done on Days 6, 10, and 16 (designated as days 1, 5, and 11 in the study protocol)" },{ "SecondaryOutcomeMeasure":"Apparent volume of distribution [V/F] for Tivantinib and its major metabolites, HPM4, HPM5, HPM6, and HPM8", "SecondaryOutcomeTimeFrame":"Pharmacokinetic sampling will be done on Days 6, 10, and 16 (designated as days 1, 5, and 11 in the study protocol)" } ] } }, "EligibilityModule":{ "EligibilityCriteria":"Inclusion Criteria:\n\nHave a histologically or cytologically confirmed advanced solid tumor at screening;\nMale or female ≥ 18 years of age;\nSubjects (male and female) of childbearing potential must agree to use double barrier contraceptive measures or avoid intercourse during the study and for 90 days after the last dose of study drug. In addition, all female subjects of childbearing potential must have a negative pregnancy test result before initiating study treatment;\nAn Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2;\n\nAdequate bone marrow, liver, clotting, and renal function, defined as:\n\nPlatelet count ≥ 100 x 10^9/L, Hemoglobin (Hb) ≥ 9.0 g/dL, ANC ≥ 1.5 × 109/L, Total bilirubin ≤ 1.5 x the upper limit of normal (ULN), Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN (≤ 5 x ULN for subjects with liver metastases), International normalized ratio ≤ 1.5, Serum creatinine ≤ 1.5 x ULN;\n\nAble to provide written informed consent, comply with protocol visits and procedures, be able to take oral medication, and not have any active infection or chronic co-morbidity that would interfere with therapy; and\nSubjects must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign and date an IRB approved ICF (including HIPAA authorization, if applicable) before performance of any study specific procedures or tests.\n\nExclusion Criteria:\n\nHistory of cardiac disease:\n\nActive coronary artery disease, defined as myocardial infarction (MI), unstable angina, coronary artery bypass graft, or stenting within 6 months prior to study entry (an MI that occurred > 6 months prior to study entry is permitted);\nEvidence of uncontrolled symptomatic bradycardia or other cardiac arrhythmia defined as ≥ Grade 2 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4, or uncontrolled hypertension;\nActive, clinically serious infection(s) defined as ≥ Grade 2 according to NCI CTCAE, version 4;\nFamily or personal history of coagulopathy;\nHistory of hypersensitivity or adverse reactions to omeprazole, digoxin, warfarin, caffeine, midazolam, or vitamin K;\nKnown metastatic brain or meningeal tumors, unless the subject is > 3 months from definitive therapy and clinically stable (supportive therapy with steroids or anticonvulsant medications is allowed) with respect to the tumor at the time of first dose of study drug;\nPregnant or breastfeeding;\nAny major surgical procedure within 3 weeks prior to first dose of study drug;\nSignificant gastrointestinal disorder(s), in the opinion of the Investigator (eg, Crohn's disease, ulcerative colitis, extensive gastric resection);\nReceived anti-cancer therapy, including antibody, retinoid, or hormonal treatment (except megestrol acetate as supportive care), and radiation, within 3 weeks before dosing. Prior and concurrent use of hormone replacement therapy, the use of gonadotropin-releasing hormone modulators for prostate cancer, and the use of somatostatin analogs for neuroendocrine tumors are permitted;\nReceived any other investigational drug within 3 weeks prior to dosing;\nReceived tivantinib as prior therapy;\nSubstance abuse or medical, psychological, or social conditions that may, in the opinion of the Investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results;\nAny condition that is unstable or that could jeopardize the safety of the subject and the subject's protocol compliance, including known human immunodeficiency virus, hepatitis B virus, or hepatitis C virus infection;\nInability to swallow oral medications that could interfere with the absorption of tivantinib;\nAdministration or possibility of initiating or continuing any treatment with any known Cytochrome P450 (CYP)3A4, CYP2C19, CYP1A2, CYP2C9, and P-glycoprotein enzyme-altering drugs (inducer or inhibitor) or non-drug agents or systemic gastric pH modifiers (ie, ranitidine, proton pump inhibitors etc) within the 14 days prior to dosing and/or during the primary objective phase after initiation of the study treatment; or\nClinical diagnosis of hepatic impairment from chronic liver cirrhosis with confirmation by either previous liver biopsy or imaging, regardless of liver function test results at screening.", "HealthyVolunteers":"No", "Gender":"All", "MinimumAge":"18 Years", "StdAgeList":{ "StdAge":[ "Adult", "Older Adult" ] } }, "ContactsLocationsModule":{ "OverallOfficialList":{ "OverallOfficial":[ { "OverallOfficialName":"Hamim Zahir, BPharm, PhD", "OverallOfficialAffiliation":"Daiichi Sankyo UK Ltd.", "OverallOfficialRole":"Study Director" } ] }, "LocationList":{ "Location":[ { "LocationFacility":"START - South Texas Accelerated Research Therapeutics, LLC", "LocationCity":"San Antonio", "LocationState":"Texas", "LocationZip":"78229", "LocationCountry":"United States" } ] } }, "IPDSharingStatementModule":{ "IPDSharing":"Yes", "IPDSharingDescription":"De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/", "IPDSharingInfoTypeList":{ "IPDSharingInfoType":[ "Study Protocol", "Statistical Analysis Plan (SAP)", "Clinical Study Report (CSR)" ] }, "IPDSharingTimeFrame":"Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.", "IPDSharingAccessCriteria":"Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.", "IPDSharingURL":"https://vivli.org/ourmember/daiichi-sankyo/" } }, "DerivedSection":{ "MiscInfoModule":{ "VersionHolder":"April 22, 2020" }, "InterventionBrowseModule":{ "InterventionMeshList":{ "InterventionMesh":[ { "InterventionMeshId":"D000014812", "InterventionMeshTerm":"Vitamin K" },{ "InterventionMeshId":"D000004077", "InterventionMeshTerm":"Digoxin" },{ "InterventionMeshId":"D000008874", "InterventionMeshTerm":"Midazolam" },{ "InterventionMeshId":"D000002110", "InterventionMeshTerm":"Caffeine" },{ "InterventionMeshId":"D000009853", "InterventionMeshTerm":"Omeprazole" },{ "InterventionMeshId":"D000014859", "InterventionMeshTerm":"Warfarin" } ] }, "InterventionAncestorList":{ "InterventionAncestor":[ { "InterventionAncestorId":"D000014815", "InterventionAncestorTerm":"Vitamins" },{ "InterventionAncestorId":"D000018977", "InterventionAncestorTerm":"Micronutrients" },{ "InterventionAncestorId":"D000078622", "InterventionAncestorTerm":"Nutrients" },{ "InterventionAncestorId":"D000006133", "InterventionAncestorTerm":"Growth Substances" },{ "InterventionAncestorId":"D000045505", "InterventionAncestorTerm":"Physiological Effects of Drugs" },{ "InterventionAncestorId":"D000000759", "InterventionAncestorTerm":"Adjuvants, Anesthesia" },{ "InterventionAncestorId":"D000006993", "InterventionAncestorTerm":"Hypnotics and Sedatives" },{ "InterventionAncestorId":"D000002492", "InterventionAncestorTerm":"Central Nervous System Depressants" },{ "InterventionAncestorId":"D000014151", "InterventionAncestorTerm":"Anti-Anxiety Agents" },{ "InterventionAncestorId":"D000014149", "InterventionAncestorTerm":"Tranquilizing Agents" },{ "InterventionAncestorId":"D000011619", "InterventionAncestorTerm":"Psychotropic Drugs" },{ "InterventionAncestorId":"D000018686", "InterventionAncestorTerm":"Anesthetics, Intravenous" },{ "InterventionAncestorId":"D000018681", "InterventionAncestorTerm":"Anesthetics, General" },{ "InterventionAncestorId":"D000000777", "InterventionAncestorTerm":"Anesthetics" },{ "InterventionAncestorId":"D000018757", "InterventionAncestorTerm":"GABA Modulators" },{ "InterventionAncestorId":"D000018682", "InterventionAncestorTerm":"GABA Agents" },{ "InterventionAncestorId":"D000018377", "InterventionAncestorTerm":"Neurotransmitter Agents" },{ "InterventionAncestorId":"D000045504", "InterventionAncestorTerm":"Molecular Mechanisms of Pharmacological Action" },{ "InterventionAncestorId":"D000000925", "InterventionAncestorTerm":"Anticoagulants" },{ "InterventionAncestorId":"D000000897", "InterventionAncestorTerm":"Anti-Ulcer Agents" },{ "InterventionAncestorId":"D000005765", "InterventionAncestorTerm":"Gastrointestinal Agents" },{ "InterventionAncestorId":"D000054328", "InterventionAncestorTerm":"Proton Pump Inhibitors" },{ "InterventionAncestorId":"D000004791", "InterventionAncestorTerm":"Enzyme Inhibitors" },{ "InterventionAncestorId":"D000000697", "InterventionAncestorTerm":"Central Nervous System Stimulants" },{ "InterventionAncestorId":"D000010726", "InterventionAncestorTerm":"Phosphodiesterase Inhibitors" },{ "InterventionAncestorId":"D000058915", "InterventionAncestorTerm":"Purinergic P1 Receptor Antagonists" },{ "InterventionAncestorId":"D000058914", "InterventionAncestorTerm":"Purinergic Antagonists" },{ "InterventionAncestorId":"D000058905", "InterventionAncestorTerm":"Purinergic Agents" },{ "InterventionAncestorId":"D000000889", "InterventionAncestorTerm":"Anti-Arrhythmia Agents" },{ "InterventionAncestorId":"D000002316", "InterventionAncestorTerm":"Cardiotonic Agents" },{ "InterventionAncestorId":"D000020011", "InterventionAncestorTerm":"Protective Agents" },{ "InterventionAncestorId":"D000000933", "InterventionAncestorTerm":"Antifibrinolytic Agents" },{ "InterventionAncestorId":"D000050299", "InterventionAncestorTerm":"Fibrin Modulating Agents" },{ "InterventionAncestorId":"D000006490", "InterventionAncestorTerm":"Hemostatics" },{ "InterventionAncestorId":"D000003029", "InterventionAncestorTerm":"Coagulants" } ] }, "InterventionBrowseLeafList":{ "InterventionBrowseLeaf":[ { "InterventionBrowseLeafId":"M10428", "InterventionBrowseLeafName":"Midazolam", "InterventionBrowseLeafAsFound":"Midazolam", "InterventionBrowseLeafRelevance":"high" },{ "InterventionBrowseLeafId":"M16141", "InterventionBrowseLeafName":"Vitamins", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M11368", "InterventionBrowseLeafName":"Omeprazole", "InterventionBrowseLeafAsFound":"Omeprazole", "InterventionBrowseLeafRelevance":"high" },{ "InterventionBrowseLeafId":"M5848", "InterventionBrowseLeafName":"Digoxin", "InterventionBrowseLeafAsFound":"Digoxin", "InterventionBrowseLeafRelevance":"high" },{ "InterventionBrowseLeafId":"M3955", "InterventionBrowseLeafName":"Caffeine", "InterventionBrowseLeafAsFound":"Caffeine", "InterventionBrowseLeafRelevance":"high" },{ "InterventionBrowseLeafId":"M16138", "InterventionBrowseLeafName":"Vitamin K", "InterventionBrowseLeafAsFound":"Vitamin K", "InterventionBrowseLeafRelevance":"high" },{ "InterventionBrowseLeafId":"M16185", "InterventionBrowseLeafName":"Warfarin", "InterventionBrowseLeafAsFound":"Warfarin", "InterventionBrowseLeafRelevance":"high" },{ "InterventionBrowseLeafId":"M15468", "InterventionBrowseLeafName":"Trace Elements", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M19593", "InterventionBrowseLeafName":"Micronutrients", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M1986", "InterventionBrowseLeafName":"Nutrients", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M2688", "InterventionBrowseLeafName":"Anesthetics", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M8626", "InterventionBrowseLeafName":"Hypnotics and Sedatives", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M15488", "InterventionBrowseLeafName":"Anti-Anxiety Agents", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M13057", "InterventionBrowseLeafName":"Psychotropic Drugs", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M19350", "InterventionBrowseLeafName":"Anesthetics, Intravenous", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M19345", "InterventionBrowseLeafName":"Anesthetics, General", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M19411", "InterventionBrowseLeafName":"GABA Modulators", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M19088", "InterventionBrowseLeafName":"Neurotransmitter Agents", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M2825", "InterventionBrowseLeafName":"Anticoagulants", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M2769", "InterventionBrowseLeafName":"Antacids", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M2800", "InterventionBrowseLeafName":"Anti-Ulcer Agents", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M7464", "InterventionBrowseLeafName":"Gastrointestinal Agents", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M26217", "InterventionBrowseLeafName":"Proton Pump Inhibitors", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M2610", "InterventionBrowseLeafName":"Central Nervous System Stimulants", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M12212", "InterventionBrowseLeafName":"Phosphodiesterase Inhibitors", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M2794", "InterventionBrowseLeafName":"Anti-Arrhythmia Agents", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M4154", "InterventionBrowseLeafName":"Cardiotonic Agents", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M20453", "InterventionBrowseLeafName":"Protective Agents", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M2833", "InterventionBrowseLeafName":"Antifibrinolytic Agents", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M8159", "InterventionBrowseLeafName":"Hemostatics", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M4842", "InterventionBrowseLeafName":"Coagulants", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"T370", "InterventionBrowseLeafName":"Caffeine", "InterventionBrowseLeafAsFound":"Caffeine", "InterventionBrowseLeafRelevance":"high" },{ "InterventionBrowseLeafId":"T481", "InterventionBrowseLeafName":"Vitamin K", "InterventionBrowseLeafAsFound":"Vitamin K", "InterventionBrowseLeafRelevance":"high" },{ "InterventionBrowseLeafId":"T458", "InterventionBrowseLeafName":"Phylloquinone", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"T449", "InterventionBrowseLeafName":"Menadione", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"T450", "InterventionBrowseLeafName":"Menaquinone", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"T452", "InterventionBrowseLeafName":"Naphthoquinone", "InterventionBrowseLeafRelevance":"low" } ] }, "InterventionBrowseBranchList":{ "InterventionBrowseBranch":[ { "InterventionBrowseBranchAbbrev":"AdjAn", "InterventionBrowseBranchName":"Adjuvants, Anesthesia" },{ "InterventionBrowseBranchAbbrev":"CNSDep", "InterventionBrowseBranchName":"Central Nervous System Depressants" },{ "InterventionBrowseBranchAbbrev":"PsychDr", "InterventionBrowseBranchName":"Psychotropic Drugs" },{ "InterventionBrowseBranchAbbrev":"All", "InterventionBrowseBranchName":"All Drugs and Chemicals" },{ "InterventionBrowseBranchAbbrev":"Micro", "InterventionBrowseBranchName":"Micronutrients" },{ "InterventionBrowseBranchAbbrev":"Gast", "InterventionBrowseBranchName":"Gastrointestinal Agents" },{ "InterventionBrowseBranchAbbrev":"AnArAg", "InterventionBrowseBranchName":"Anti-Arrhythmia Agents" },{ "InterventionBrowseBranchAbbrev":"CaAg", "InterventionBrowseBranchName":"Cardiotonic Agents" },{ "InterventionBrowseBranchAbbrev":"CNSSti", "InterventionBrowseBranchName":"Central Nervous System Stimulants" },{ "InterventionBrowseBranchAbbrev":"Coag", "InterventionBrowseBranchName":"Coagulants" },{ "InterventionBrowseBranchAbbrev":"AnCoag", "InterventionBrowseBranchName":"Anticoagulants" },{ "InterventionBrowseBranchAbbrev":"Ot", "InterventionBrowseBranchName":"Other Dietary Supplements" },{ "InterventionBrowseBranchAbbrev":"Vi", "InterventionBrowseBranchName":"Vitamins" } ] } } } } } }