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
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 April 15, 2014