Ignite Creation Date:
2025-12-24 @ 4:41 PM
Ignite Modification Date:
2025-12-27 @ 12:08 PM
Study NCT ID:
NCT01133366
Status:
COMPLETED
Last Update Posted:
2016-08-03
First Post:
2010-05-27
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
A Study to Determine the Effects of Multiple Doses of Mipomersen (200 mg SC) on the Pharmacodynamics and Pharmacokinetics of Single-dose Warfarin
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D014859', 'term': 'Warfarin'}, {'id': 'C524142', 'term': 'mipomersen'}], 'ancestors': [{'id': 'D015110', 'term': '4-Hydroxycoumarins'}, {'id': 'D003374', 'term': 'Coumarins'}, {'id': 'D001578', 'term': 'Benzopyrans'}, {'id': 'D011714', 'term': 'Pyrans'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 18}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2010-05'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-08', 'completionDateStruct': {'date': '2010-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-08-01', 'studyFirstSubmitDate': '2010-05-27', 'studyFirstSubmitQcDate': '2010-05-27', 'lastUpdatePostDateStruct': {'date': '2016-08-03', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2010-05-28', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2010-05', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Area under the effect curve (AUC), for INR (international normalized ratio), PT (prothrombin time), and aPTT (activated partial thromboplastin time)', 'timeFrame': 'Serial sampling up to 144 hours post dose'}, {'measure': 'Maximal Value (MAX) for INR, PT and aPTT', 'timeFrame': 'Serial sampling up to 144 hours post dose'}, {'measure': 'Time of maximal effect (Tmax) for INR, PT, and aPTT', 'timeFrame': 'Serial sampling up to 144 hours post dose'}], 'secondaryOutcomes': [{'measure': 'Warfarin Plasma Pharmacokinetic parameters (AUC 0-t, AUC 0-inf, Maximum Concentration (Cmax))', 'timeFrame': 'Serial PK sampling up to 144 hours post dose'}, {'measure': 'Mipomersen Plasma Pharmacokinetic parameters (AUC0-t, AUC0-inf, Cmax)', 'timeFrame': 'Serial PK sampling up to 24 hours post dose'}, {'measure': 'Incidence of treatment-emergent Adverse Events', 'timeFrame': 'Through Day 78'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['ISIS301012', 'antisense', 'ApoB (Apolipoprotein B)', 'LDL (low density lipoprotein)', 'mipomersen'], 'conditions': ['Healthy']}, 'descriptionModule': {'briefSummary': 'The purpose of this study is to assess how blood clotting and thinning time is effected when a single dose of warfarin is given alone and when a single dose of warfarin is given with mipomersen; to assess the blood levels of a single dose of warfarin, a single dose of mipomersen, and a single dose of warfarin when given with mipomersen; and to assess the safety of mipomersen when given with or without warfarin.', 'detailedDescription': 'This will be a Phase 1, open-label, single-sequence, 2-period, crossover study to determine the effect of multiple doses of mipomersen (200 mg SC given every other day for a total of 4 doses) on the PD and PK of warfarin and to evaluate the PK of mipomersen when administered alone and in combination with warfarin. Subjects will be admitted to the clinic on Day -1 until discharge from the clinic on Day 18 and return for outpatient visits on Days 19, 20, and 78. All subjects will receive a single 25-mg oral dose of warfarin given alone on Day 1 (designated the reference treatment). All subjects will then receive 200-mg SC doses of mipomersen given every other day on Days 8, 10, 12, and 14 (total of 800 mg mipomersen) with a single 25-mg oral dose of warfarin also given on Day 14 (combination designated the test treatment).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT'], 'maximumAge': '45 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Written informed consent before any study-related procedure is performed.\n* Body mass index (BMI) between 18 and 32 kg/m2, inclusive.\n* No clinically significant abnormalities based on medical history, laboratory assessments, vital sign, 12-lead electrocardiogram (ECG) results, and physical examination.\n* Subjects willing and able to follow a prescribed diet.\n* Subjects have not consumed nicotine or nicotine-containing products for at least 6 months before Screening.\n* Subjects are nonpregnant and nonlactating, surgically sterile, postmenopausal, abstinent, or the subject or partner is willing to use a reliable method of contraception during the study and for 5 months after mipomersen dosing.\n\nExclusion Criteria:\n\n* Poor metabolizer of warfarin as determined by CYP2C9 genotype testing.\n* Clinically significant PT, aPTT, INR, protein C, protein S, or platelet count results or hematuria.\n* Abnormal prolongation of skin bleeding time or a personal or family history of coagulation or bleeding disorders, vascular malformations including aneurysms, or venous thromboembolism.\n* Active or recurring clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurologic, psychiatric, immunologic, hematologic, gastrointestinal, or metabolic disease.\n* Active malignancy of any type other than nonmelanomatous skin malignancies.\n* Use of any prescribed or over-the-counter concomitant medications within 14 days before the first dose of investigational product without approval of the Investigator and Sponsor.\n* Positive test result for drugs of abuse, alcohol, or cotinine or history of alcohol abuse or drug addiction.\n* Positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or HIV.'}, 'identificationModule': {'nctId': 'NCT01133366', 'briefTitle': 'A Study to Determine the Effects of Multiple Doses of Mipomersen (200 mg SC) on the Pharmacodynamics and Pharmacokinetics of Single-dose Warfarin', 'organization': {'class': 'INDUSTRY', 'fullName': 'Kastle Therapeutics, LLC'}, 'officialTitle': 'A Drug-Drug Interaction Study to Assess the Effects of Multiple Doses of Mipomersen (200 mg SC) on Single-Dose Warfarin (25 mg) Pharmacodynamics and Pharmacokinetics in Healthy Adult Subjects', 'orgStudyIdInfo': {'id': 'MIPO2900509'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'warfarin alone', 'interventionNames': ['Drug: warfarin sodium']}, {'type': 'EXPERIMENTAL', 'label': 'warfarin with mipomersen', 'interventionNames': ['Drug: mipomersen sodium; warfarin sodium']}], 'interventions': [{'name': 'warfarin sodium', 'type': 'DRUG', 'otherNames': ['Coumadin®'], 'description': '25 mg of warfarin oral (single dose)', 'armGroupLabels': ['warfarin alone']}, {'name': 'mipomersen sodium; warfarin sodium', 'type': 'DRUG', 'otherNames': ['Coumadin®'], 'description': '200 mg of mipomersen subcutaneous (SC) (4 doses) plus a single 25 mg of warfarin oral administered with the final mipomersen SC dose', 'armGroupLabels': ['warfarin with mipomersen']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Austin', 'state': 'Texas', 'country': 'United States', 'facility': 'PPD Development, LP', 'geoPoint': {'lat': 30.26715, 'lon': -97.74306}}], 'overallOfficials': [{'name': 'Medical Monitor', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Genzyme, a Sanofi Company'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Kastle Therapeutics, LLC', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Ionis Pharmaceuticals, Inc.', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}