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.
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
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
25 mg of warfarin oral (single dose)
200 mg of mipomersen subcutaneous (SC) (4 doses) plus a single 25 mg of warfarin oral administered with the final mipomersen SC dose
PPD Development, LP
Austin, Texas, United States
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
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
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