{ "FullStudy":{ "Rank":217934, "Study":{ "ProtocolSection":{ "IdentificationModule":{ "NCTId":"NCT01514929", "OrgStudyIdInfo":{ "OrgStudyId":"ACHN-490-006" }, "Organization":{ "OrgFullName":"Achaogen, Inc.", "OrgClass":"INDUSTRY" }, "BriefTitle":"A Study to Evaluate the Effect of IV ACHN-490 Injection on the QT/QTc Interval in Healthy Volunteers", "OfficialTitle":"A Randomized, Double-Blind, Placebo and Positive-Controlled, Crossover Study to Evaluate the Effect of IV ACHN-490 Injection on the QT/QTc Interval in Healthy Volunteers" }, "StatusModule":{ "StatusVerifiedDate":"May 2012", "OverallStatus":"Completed", "ExpandedAccessInfo":{ "HasExpandedAccess":"No" }, "StartDateStruct":{ "StartDate":"October 2011" }, "CompletionDateStruct":{ "CompletionDate":"March 2012", "CompletionDateType":"Actual" }, "StudyFirstSubmitDate":"November 28, 2011", "StudyFirstSubmitQCDate":"January 18, 2012", "StudyFirstPostDateStruct":{ "StudyFirstPostDate":"January 23, 2012", "StudyFirstPostDateType":"Estimate" }, "LastUpdateSubmitDate":"May 8, 2012", "LastUpdatePostDateStruct":{ "LastUpdatePostDate":"May 9, 2012", "LastUpdatePostDateType":"Estimate" } }, "SponsorCollaboratorsModule":{ "ResponsibleParty":{ "ResponsiblePartyType":"Sponsor" }, "LeadSponsor":{ "LeadSponsorName":"Achaogen, Inc.", "LeadSponsorClass":"INDUSTRY" }, "CollaboratorList":{ "Collaborator":[ { "CollaboratorName":"Department of Health and Human Services", "CollaboratorClass":"FED" } ] } }, "OversightModule":{ "OversightHasDMC":"Yes" }, "DescriptionModule":{ "BriefSummary":"The purpose of this study is to determine if the study drug, ACHN-490 Injection, affects the QT interval in normal volunteers. The hypothesis is that the drug will not cause an increase in the QT interval." }, "ConditionsModule":{ "ConditionList":{ "Condition":[ "Cardiac Effects in Normal Healthy Volunteers" ] }, "KeywordList":{ "Keyword":[ "Thorough QT" ] } }, "DesignModule":{ "StudyType":"Interventional", "PhaseList":{ "Phase":[ "Phase 1" ] }, "DesignInfo":{ "DesignAllocation":"Randomized", "DesignInterventionModel":"Crossover Assignment", "DesignPrimaryPurpose":"Treatment", "DesignMaskingInfo":{ "DesignMasking":"Double", "DesignWhoMaskedList":{ "DesignWhoMasked":[ "Participant", "Investigator" ] } } }, "EnrollmentInfo":{ "EnrollmentCount":"64", "EnrollmentType":"Actual" } }, "ArmsInterventionsModule":{ "ArmGroupList":{ "ArmGroup":[ { "ArmGroupLabel":"Supratherapeutic Dose", "ArmGroupType":"Experimental", "ArmGroupDescription":"20mg/kg ACHN-490 Injection", "ArmGroupInterventionList":{ "ArmGroupInterventionName":[ "Drug: ACHN-490 Injection" ] } },{ "ArmGroupLabel":"Possible Therapeutic Dose", "ArmGroupType":"Experimental", "ArmGroupDescription":"15mg/kg ACHN-490 Injection", "ArmGroupInterventionList":{ "ArmGroupInterventionName":[ "Drug: ACHN-490 Injection" ] } },{ "ArmGroupLabel":"Moxifloxacin", "ArmGroupType":"Active Comparator", "ArmGroupDescription":"400mg moxifloxacin", "ArmGroupInterventionList":{ "ArmGroupInterventionName":[ "Drug: Moxifloxacin" ] } },{ "ArmGroupLabel":"Placebo", "ArmGroupType":"Placebo Comparator", "ArmGroupDescription":"Placebo", "ArmGroupInterventionList":{ "ArmGroupInterventionName":[ "Drug: Placebo" ] } } ] }, "InterventionList":{ "Intervention":[ { "InterventionType":"Drug", "InterventionName":"ACHN-490 Injection", "InterventionDescription":"20mg/kg IV 30 minute infusion given once", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Supratherapeutic Dose" ] } },{ "InterventionType":"Drug", "InterventionName":"ACHN-490 Injection", "InterventionDescription":"15mg/kg IV 30 minute infusion given once", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Possible Therapeutic Dose" ] } },{ "InterventionType":"Drug", "InterventionName":"Moxifloxacin", "InterventionDescription":"400mg oral pill given once", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Moxifloxacin" ] } },{ "InterventionType":"Drug", "InterventionName":"Placebo", "InterventionDescription":"Placebo oral pill given once", "InterventionArmGroupLabelList":{ "InterventionArmGroupLabel":[ "Placebo" ] } } ] } }, "OutcomesModule":{ "PrimaryOutcomeList":{ "PrimaryOutcome":[ { "PrimaryOutcomeMeasure":"Safety", "PrimaryOutcomeDescription":"In Part 1, the safety and tolerability of a single 20 mg/kg dose of ACHN-490 Injection will be assessed by measuring adverse events, blood pressure and other vital sign measurements, incidence and magnitude of clinically significant changes from baseline in clinical laboratory values (hematology, chemistry, and urinalysis), and physical examination, through 24 hours after study drug administration or resolution of all adverse events.", "PrimaryOutcomeTimeFrame":"1 day" },{ "PrimaryOutcomeMeasure":"Effect of ACHN-490 Injection on QTcF", "PrimaryOutcomeDescription":"The primary endpoint for Part 2 of this study is the time-matched change from baseline in QTcF within 24 hours of receiving study drug.", "PrimaryOutcomeTimeFrame":"24 hours" } ] }, "SecondaryOutcomeList":{ "SecondaryOutcome":[ { "SecondaryOutcomeMeasure":"PK Parameters", "SecondaryOutcomeDescription":"The secondary endpoints for Part 1 of this study will include relevant PK parameters such as AUC0-t, AUC0-∞, CLT, Vss, Cmax, Tmax, and t1/2 measured for 24 hours after receiving study drug.", "SecondaryOutcomeTimeFrame":"24 hours" },{ "SecondaryOutcomeMeasure":"ECG Parameters", "SecondaryOutcomeDescription":"Part 2 of the study will measure the effect of ACHN-490 Injection compared to placebo within 24 hours of study drug administration on heart rate, PR interval, QRS interval, QTcB, uncorrected QT interval, RR intervals, change in ST and T-wave morphology, and categorical change in QTc variables.", "SecondaryOutcomeTimeFrame":"24 hours" },{ "SecondaryOutcomeMeasure":"PK Parameters", "SecondaryOutcomeDescription":"Part 2 of this study will measure multiple PK parameters such as AUC0-t, AUC0-∞, CLT, Vss, Cmax, Tmax, and t1/2 measured for 24 hours after receiving study drug.", "SecondaryOutcomeTimeFrame":"24 hours" },{ "SecondaryOutcomeMeasure":"Correlation between drug concentration and QTc", "SecondaryOutcomeDescription":"Part 2 of this study will measure the correlation between the QTc change from baseline and plasma concentrations of ACHN-490 Injection within 24 hours of study drug administration.", "SecondaryOutcomeTimeFrame":"24 hours" },{ "SecondaryOutcomeMeasure":"Safety and tolerability", "SecondaryOutcomeDescription":"Part 2 of this study will measure safety and tolerability of ACHN-490 Injection including adverse events, incidence and magnitude of clinically significant changes from baseline in clinical laboratory values (hematology, chemistry, and urinalysis) and physical examination; all for up to 44 days after receiving study drug.", "SecondaryOutcomeTimeFrame":"Up to 44 days" } ] } }, "EligibilityModule":{ "EligibilityCriteria":"Inclusion Criteria:\n\nMale and female subjects between 18 and 50 years of age and with a body mass index ≥ 18 to ≤ 33 kg/m2, and weight of ≥ 40 to ≤ 100 kg inclusive.\nSubject is in good health as judged by the investigator based on the laboratory criteria and no clinically significant findings on the medical history or physical examination.\nFemales of child-bearing potential (defined as less than one year post-menopause) are eligible for enrollment if they are not breast feeding, they have a negative serum pregnancy test before study entry, and they are using a highly effective method of contraception for at least 3 months before study drug administration, during the study, and for at least 6 months after study completion.\nSubjects who are willing to comply with all study activities and procedures and have provided written informed consent prior to any study procedures and have signed and dated a Health Insurance Portability and Accountability Act (HIPAA) authorization form.\n\nExclusion Criteria:\n\nA history of additional risk factors for TdP.\nUnstable cardiovascular disease, including recent myocardial infarction or cardiac arrhythmia.\nSustained supine systolic blood pressure >150 mmHg, or <110 mmHg in Part 1 or <100mmHg in Part 2, or a diastolic blood pressure >95 mmHg at screening or baseline.\nA resting pulse rate at rest, taken during screening, of <40 bpm or >100 bpm.\nAn abnormal screening ECG indicating a second- or third-degree atrioventricular (AV) block, or one or more of the following: QRS >110 milliseconds (msec), QTcB >470 msec for females or 450 msec for males, PR interval >240 msec, or any rhythm other than sinus rhythm, which is interpreted by the Investigator to be clinically significant.\nUncontrolled hypertension, asthma, unstable diabetes (type I or type II), thyroid disease, seizures, myasthenia gravis, or any other neuromuscular disorder.\nPositive results at screening for hepatitis B virus, hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection.\nHistory of central nervous system disorders, epilepsy or known seizure disorder (excluding a history of childhood febrile seizures).\nThe subject has a history of any cancer, except basal cell or stage 1 squamous cell carcinoma of the skin, which has not been in remission for at least 5 years prior to the first dose of study drug.\nSubjects who have any condition possibly affecting drug absorption.\nHistory of significant hearing loss or a family history of hearing loss, excluding age related (≥ age 65) hearing loss. A prior diagnosis of sensorineural hearing loss or Ménière's disease.\nClinically significant illness, including viral syndromes within 3 weeks of dosing.\nThe use of concomitant medications that prolong the QT/QTc interval.\nUsed prescription medications, over-the-counter (OTC) medications, investigational medications/therapy, vitamins, or nicotine-containing products (eg, cigarettes, cigars, chewing tobacco, snuff, etc.) within 28 days or 5 half-lives, whichever is longer, before dosing of ACHN-490 Injection.\nUsed aminoglycosides within 6 months prior to IMP administration.\nUsed herbal preparations including St. John's wort, ginseng, kava kava, ginkgo biloba, melatonin, and other nutraceuticals within 28 days prior to IMP administration.\nConsumed caffeine- or xanthine-containing products (eg, tea, coffee, chocolate, cola, etc.), Seville oranges (sour), grapefruit, grapefruit juice, or fish liver oils within 72 hours prior to IMP administration.\nCurrent participation in a clinical study of an investigational product.\nConsumed more than 28 units of ethanol per week at any time in the 6 months before dosing (1 unit of ethanol is equivalent to 8 ounces of beer, 4 ounces of wine, or 1 ounce of spirits) or history of alcoholism and/or drug/chemical abuse. Also, consumption of any amount of ethanol within 72 hours of ACHN-490 Injection dosing.\nDonated blood or blood components within 60 days prior to receiving study drug.\nWomen who are pregnant (or planning to become pregnant within the next 3 months) or currently breastfeeding.\nPrevious participation in this or any other ACHN-490 Injection study.\nKnown hypersensitivity to aminoglycosides or any component of the ACHN-490 Injection.\nSubjects with poor venous access.\nUnable to understand verbal or written English or any other language for which a certified translation of the informed consent is not available.\nAny other medical, psychological, or social condition which, in the opinion of the PI or the medical monitor, would prevent the subject from fully participating in the study would represent a concern for study compliance or would constitute a safety concern to the subject.\nAn employee of the investigator or study center with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as a family member of the employee or investigator.\n* (Part 1 only) * Acceptable and reproducible spirometry measurements defined as: forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 80% of predicted or FEV1/FVC ratio <70% of predicted. See Appendix 7 for definitions of acceptability and reproducibility.\n* (Part 2 only) * Known hypersensitivity to moxifloxacin or other quinolones.\n* (Part 2 only) * Taken antacids, sucralfate, multivitamins, or other products with multivalent cations within 8 hours before oral dose in Part 2 or need to take any of the above within 4 hours after the dose administration.\n* (Part 2 only) * Taken warfarin or Class IA or Class III antiarrhythmics within one week prior to study drug administration or expected to need to take any of the above during the study period.\n* (Part 2 only) * Participation in Part 1 of the study.", "HealthyVolunteers":"Accepts Healthy Volunteers", "Gender":"All", "MinimumAge":"18 Years", "MaximumAge":"50 Years", "StdAgeList":{ "StdAge":[ "Adult" ] } }, "ContactsLocationsModule":{ "OverallOfficialList":{ "OverallOfficial":[ { "OverallOfficialName":"Medical Director", "OverallOfficialAffiliation":"Achaogen, Inc.", "OverallOfficialRole":"Study Director" } ] }, "LocationList":{ "Location":[ { "LocationFacility":"Investigational Site", "LocationCity":"West Bend", "LocationState":"Wisconsin", "LocationZip":"53095", "LocationCountry":"United States" } ] } } }, "DerivedSection":{ "MiscInfoModule":{ "VersionHolder":"April 22, 2020" }, "InterventionBrowseModule":{ "InterventionMeshList":{ "InterventionMesh":[ { "InterventionMeshId":"D000077266", "InterventionMeshTerm":"Moxifloxacin" } ] }, "InterventionAncestorList":{ "InterventionAncestor":[ { "InterventionAncestorId":"D000000900", "InterventionAncestorTerm":"Anti-Bacterial Agents" },{ "InterventionAncestorId":"D000000890", "InterventionAncestorTerm":"Anti-Infective Agents" },{ "InterventionAncestorId":"D000059005", "InterventionAncestorTerm":"Topoisomerase II Inhibitors" },{ "InterventionAncestorId":"D000059003", "InterventionAncestorTerm":"Topoisomerase Inhibitors" },{ "InterventionAncestorId":"D000004791", "InterventionAncestorTerm":"Enzyme Inhibitors" },{ "InterventionAncestorId":"D000045504", "InterventionAncestorTerm":"Molecular Mechanisms of Pharmacological Action" },{ "InterventionAncestorId":"D000000970", "InterventionAncestorTerm":"Antineoplastic Agents" } ] }, "InterventionBrowseLeafList":{ "InterventionBrowseLeaf":[ { "InterventionBrowseLeafId":"M1722", "InterventionBrowseLeafName":"Moxifloxacin", "InterventionBrowseLeafAsFound":"Moxifloxacin", "InterventionBrowseLeafRelevance":"high" },{ "InterventionBrowseLeafId":"M140649", "InterventionBrowseLeafName":"Norgestimate, ethinyl estradiol drug combination", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M2803", "InterventionBrowseLeafName":"Anti-Bacterial Agents", "InterventionBrowseLeafRelevance":"low" },{ "InterventionBrowseLeafId":"M2795", "InterventionBrowseLeafName":"Anti-Infective Agents", "InterventionBrowseLeafRelevance":"low" } ] }, "InterventionBrowseBranchList":{ "InterventionBrowseBranch":[ { "InterventionBrowseBranchAbbrev":"Infe", "InterventionBrowseBranchName":"Anti-Infective Agents" },{ "InterventionBrowseBranchAbbrev":"ANeo", "InterventionBrowseBranchName":"Antineoplastic Agents" },{ "InterventionBrowseBranchAbbrev":"All", "InterventionBrowseBranchName":"All Drugs and Chemicals" },{ "InterventionBrowseBranchAbbrev":"Repr", "InterventionBrowseBranchName":"Reproductive Control Agents" } ] } } } } } }