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

NCT01133366 | Completed Phase 1 DMC

• 1 other identifier: MIPO2900509
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy

Keywords

ISIS301012; antisense; ApoB (Apolipoprotein B); LDL (low density lipoprotein); mipomersen

Outcome Measures

Primary Outcomes (3)

• Area under the effect curve (AUC), for INR (international normalized ratio), PT (prothrombin time), and aPTT (activated partial thromboplastin time)

  Serial sampling up to 144 hours post dose

• Maximal Value (MAX) for INR, PT and aPTT

  Serial sampling up to 144 hours post dose

• Time of maximal effect (Tmax) for INR, PT, and aPTT

  Serial sampling up to 144 hours post dose

Secondary Outcomes (3)

• Warfarin Plasma Pharmacokinetic parameters (AUC 0-t, AUC 0-inf, Maximum Concentration (Cmax))

  Serial PK sampling up to 144 hours post dose

• Mipomersen Plasma Pharmacokinetic parameters (AUC0-t, AUC0-inf, Cmax)

  Serial PK sampling up to 24 hours post dose

• Incidence of treatment-emergent Adverse Events

  Through Day 78

Study Arms (2)

warfarin alone

ACTIVE COMPARATOR

Drug: warfarin sodium

warfarin with mipomersen

EXPERIMENTAL

Drug: mipomersen sodium; warfarin sodium

Interventions

warfarin sodium DRUG

25 mg of warfarin oral (single dose)

Also known as: Coumadin®

warfarin alone

mipomersen sodium; warfarin sodium DRUG

200 mg of mipomersen subcutaneous (SC) (4 doses) plus a single 25 mg of warfarin oral administered with the final mipomersen SC dose

Also known as: Coumadin®

warfarin with mipomersen

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Kastle Therapeutics, LLC: lead
• Ionis Pharmaceuticals, Inc.: collaborator

Study Sites (1)

PPD Development, LP

Austin, Texas, United States

Location

MeSH Terms

Interventions

Warfarin; mipomersen

Intervention Hierarchy (Ancestors)

4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2010
• First Posted: May 28, 2010
• Study Start: May 1, 2010
• Primary Completion: May 1, 2010
• Study Completion: July 1, 2010
• Last Updated: August 3, 2016

Record last verified: 2016-08

Locations

US (1)