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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Maximal Value (MAX) for INR, PT and aPTT
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
warfarin alone
干预措施: warfarin sodium (Drug)
warfarin with mipomersen
干预措施: mipomersen sodium; warfarin sodium (Drug)
结局指标
主要结局
Maximal Value (MAX) for INR, PT and aPTT
时间窗: Serial sampling up to 144 hours post dose
Area under the effect curve (AUC), for INR (international normalized ratio), PT (prothrombin time), and aPTT (activated partial thromboplastin time)
时间窗: Serial sampling up to 144 hours post dose
Time of maximal effect (Tmax) for INR, PT, and aPTT
时间窗: Serial sampling up to 144 hours post dose
次要结局
- 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)