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

This study has been completed.
Sponsor:
Collaborator:
Isis Pharmaceuticals
Information provided by:
Genzyme, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT01133366
First received: May 27, 2010
Last updated: October 28, 2010
Last verified: October 2010
  Purpose

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 Intervention Phase
Healthy
Drug: warfarin sodium
Drug: mipomersen sodium; warfarin sodium
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Genzyme, a Sanofi Company:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • Maximal Value (MAX) for INR, PT and aPTT [ Time Frame: Serial sampling up to 144 hours post dose ] [ Designated as safety issue: No ]
  • Time of maximal effect (Tmax) for INR, PT, and aPTT [ Time Frame: Serial sampling up to 144 hours post dose ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Warfarin Plasma Pharmacokinetic parameters (AUC 0-t, AUC 0-inf, Maximum Concentration (Cmax)) [ Time Frame: Serial PK sampling up to 144 hours post dose ] [ Designated as safety issue: No ]
  • Mipomersen Plasma Pharmacokinetic parameters (AUC0-t, AUC0-inf, Cmax) [ Time Frame: Serial PK sampling up to 24 hours post dose ] [ Designated as safety issue: No ]
  • Incidence of treatment-emergent Adverse Events [ Time Frame: Through Day 78 ] [ Designated as safety issue: Yes ]

Enrollment: 18
Study Start Date: May 2010
Study Completion Date: July 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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®

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).

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01133366

Locations
United States, Texas
PPD Development, LP
Austin, Texas, United States
Sponsors and Collaborators
Genzyme, a Sanofi Company
Isis Pharmaceuticals
Investigators
Study Director: Medical Monitor Genzyme, a Sanofi Company
  More Information

No publications provided

Responsible Party: Medical Monitor, Genzyme Corporation
ClinicalTrials.gov Identifier: NCT01133366     History of Changes
Other Study ID Numbers: MIPO2900509
Study First Received: May 27, 2010
Last Updated: October 28, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Genzyme, a Sanofi Company:
ISIS301012
antisense
ApoB (Apolipoprotein B)
LDL (low density lipoprotein)
mipomersen

Additional relevant MeSH terms:
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 26, 2014