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Trial record 8 of 19 for:    MIPOMERSEN

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01133366
Recruitment Status : Completed
First Posted : May 28, 2010
Last Update Posted : August 3, 2016
Ionis Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Kastle Therapeutics, LLC

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: warfarin sodium Drug: mipomersen sodium; warfarin sodium Phase 1

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Study Start Date : May 2010
Actual Primary Completion Date : May 2010
Actual Study Completion Date : July 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

Arm Intervention/treatment
Active Comparator: warfarin alone Drug: warfarin sodium
25 mg of warfarin oral (single dose)
Other Name: Coumadin®

Experimental: warfarin with mipomersen 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®

Primary Outcome Measures :
  1. 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 ]
  2. Maximal Value (MAX) for INR, PT and aPTT [ Time Frame: Serial sampling up to 144 hours post dose ]
  3. Time of maximal effect (Tmax) for INR, PT, and aPTT [ Time Frame: Serial sampling up to 144 hours post dose ]

Secondary Outcome Measures :
  1. Warfarin Plasma Pharmacokinetic parameters (AUC 0-t, AUC 0-inf, Maximum Concentration (Cmax)) [ Time Frame: Serial PK sampling up to 144 hours post dose ]
  2. Mipomersen Plasma Pharmacokinetic parameters (AUC0-t, AUC0-inf, Cmax) [ Time Frame: Serial PK sampling up to 24 hours post dose ]
  3. Incidence of treatment-emergent Adverse Events [ Time Frame: Through Day 78 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01133366

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United States, Texas
PPD Development, LP
Austin, Texas, United States
Sponsors and Collaborators
Kastle Therapeutics, LLC
Ionis Pharmaceuticals, Inc.
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Study Director: Medical Monitor Genzyme, a Sanofi Company
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Responsible Party: Kastle Therapeutics, LLC Identifier: NCT01133366    
Other Study ID Numbers: MIPO2900509
First Posted: May 28, 2010    Key Record Dates
Last Update Posted: August 3, 2016
Last Verified: August 2016
Keywords provided by Kastle Therapeutics, LLC:
ApoB (Apolipoprotein B)
LDL (low density lipoprotein)
Additional relevant MeSH terms:
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Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents