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A Study to Determine the Effects of Multiple Doses of Mipomersen (200 mg SC) on the Pharmacodynamics and Pharmacokinetics of Single-dose Warfarin

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ClinicalTrials.gov Identifier: NCT01133366
Recruitment Status : Completed
First Posted : May 28, 2010
Last Update Posted : August 3, 2016
Sponsor:
Collaborator:
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Kastle Therapeutics, LLC

Tracking Information
First Submitted Date  ICMJE May 27, 2010
First Posted Date  ICMJE May 28, 2010
Last Update Posted Date August 3, 2016
Study Start Date  ICMJE May 2010
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 28, 2010)
  • Area under the effect curve (AUC), for INR (international normalized ratio), PT (prothrombin time), and aPTT (activated partial thromboplastin time) [ Time Frame: Serial sampling up to 144 hours post dose ]
  • Maximal Value (MAX) for INR, PT and aPTT [ Time Frame: Serial sampling up to 144 hours post dose ]
  • Time of maximal effect (Tmax) for INR, PT, and aPTT [ Time Frame: Serial sampling up to 144 hours post dose ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 27, 2010)
  • Area under the effect curve (AUC), for INR (international normalized ratio), PT (prothrombin time), and aPTT (activated partical thromboplastin time) [ Time Frame: Serial sampling up to 144 hours post dose ]
  • Maximal Value (MAX) for INR, PT and aPTT [ Time Frame: Serial sampling up to 144 hours post dose ]
  • Time of maximal effect (Tmax) for INR, PT, and aPTT [ Time Frame: Serial sampling up to 144 hours post dose ]
Change History Complete list of historical versions of study NCT01133366 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2010)
  • Warfarin Plasma Pharmacokinetic parameters (AUC 0-t, AUC 0-inf, Maximum Concentration (Cmax)) [ Time Frame: Serial PK sampling up to 144 hours post dose ]
  • Mipomersen Plasma Pharmacokinetic parameters (AUC0-t, AUC0-inf, Cmax) [ Time Frame: Serial PK sampling up to 24 hours post dose ]
  • Incidence of treatment-emergent Adverse Events [ Time Frame: Through Day 78 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 27, 2010)
  • Warfarin Plasma Pharmacokinetic parameters (AUC 0-t, AUC 0-inf, Cmax) [ Time Frame: Serial PK sampling up to 144 hours post dose ]
  • Mipomersen Plasma Pharmacokinetic parameters (AUC0-t, AUC0-inf, Cmax) [ Time Frame: Serial PK sampling up to 24 hours post dose ]
  • Incidence of treatment-emergent Adverse Events [ Time Frame: Through Day 78 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Determine the Effects of Multiple Doses of Mipomersen (200 mg SC) on the Pharmacodynamics and Pharmacokinetics of Single-dose Warfarin
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description 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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Healthy
Intervention  ICMJE
  • Drug: warfarin sodium
    25 mg of warfarin oral (single dose)
    Other Name: Coumadin®
  • Drug: mipomersen sodium; warfarin sodium
    200 mg of mipomersen subcutaneous (SC) (4 doses) plus a single 25 mg of warfarin oral administered with the final mipomersen SC dose
    Other Name: Coumadin®
Study Arms  ICMJE
  • Active Comparator: warfarin alone
    Intervention: Drug: warfarin sodium
  • Experimental: warfarin with mipomersen
    Intervention: Drug: mipomersen sodium; warfarin sodium
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 27, 2010)
18
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE July 2010
Actual Primary Completion Date May 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Written informed consent before any study-related procedure is performed.
  • Body mass index (BMI) between 18 and 32 kg/m2, inclusive.
  • No clinically significant abnormalities based on medical history, laboratory assessments, vital sign, 12-lead electrocardiogram (ECG) results, and physical examination.
  • Subjects willing and able to follow a prescribed diet.
  • Subjects have not consumed nicotine or nicotine-containing products for at least 6 months before Screening.
  • 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.

Exclusion Criteria:

  • Poor metabolizer of warfarin as determined by CYP2C9 genotype testing.
  • Clinically significant PT, aPTT, INR, protein C, protein S, or platelet count results or hematuria.
  • Abnormal prolongation of skin bleeding time or a personal or family history of coagulation or bleeding disorders, vascular malformations including aneurysms, or venous thromboembolism.
  • Active or recurring clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurologic, psychiatric, immunologic, hematologic, gastrointestinal, or metabolic disease.
  • Active malignancy of any type other than nonmelanomatous skin malignancies.
  • 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.
  • Positive test result for drugs of abuse, alcohol, or cotinine or history of alcohol abuse or drug addiction.
  • Positive test result for hepatitis B surface antigen, hepatitis C virus antibody, or HIV.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01133366
Other Study ID Numbers  ICMJE MIPO2900509
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Kastle Therapeutics, LLC
Study Sponsor  ICMJE Kastle Therapeutics, LLC
Collaborators  ICMJE Ionis Pharmaceuticals, Inc.
Investigators  ICMJE
Study Director: Medical Monitor Genzyme, a Sanofi Company
PRS Account Kastle Therapeutics, LLC
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP