A Randomized, Double-Blind, Vehicle-Controlled Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenously Administered PRT064445 After Dosing to Steady State With One of Four Direct/Indirect fXa Inhibitors in Healthy Volunteers
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 28
- 主要终点
- Efficacy: Percent Change From Baseline in Anti-fXa Activity at 2 Mins Following Andexanet/Placebo Administration
研究概览
简要总结
The purpose of this study is to evaluate the ability of PRT064445 to reverse the effects of several blood thinner drugs on laboratory tests. The study also is evaluating the blood levels of PRT064445 given at different doses.
详细描述
A randomized, double-blind, vehicle-controlled study to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of intravenously administered PRT064445 after dosing to steady state with one of four direct/indirect factor Xa (fXa) inhibitors in healthy volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Healthy men or women between the ages of 18 and 45 years old
排除标准
- •History (including family history) or symptoms of, or risk factors for bleeding
- •History (including family history) of or risk factors for a hypercoagulable or thrombotic condition
- •Absolute/relative contraindication to anticoagulation or treatment with specific anticoagulants
- •History of major surgery, severe trauma or bone fracture within 3 months prior to dosing; or planned surgery within 1 month after dosing
研究组 & 干预措施
Module 4 (800 mg bolus + 480 mg infusion) 8mg/min
1280 mg PRT064445: 800 mg IV at ~30 mg/min, followed by a continuous infusion of 480 mg (4 mg /min over 60 minutes)
干预措施: Placebo/Edoxaban (Combination Product)
Module 4 (800 mg bolus)
800 mg PRT064445 as a single IV bolus
干预措施: PRT064445/Edoxaban (Combination Product)
Module 4 (600 mg bolus)
600 mg PRT064445 given as a single IV bolus
干预措施: PRT064445/Edoxaban (Combination Product)
Module 4 (600 mg bolus)
600 mg PRT064445 given as a single IV bolus
干预措施: Placebo/Edoxaban (Combination Product)
Module 4 (800 mg bolus + 480 mg infusion) 8mg/min
1280 mg PRT064445: 800 mg IV at ~30 mg/min, followed by a continuous infusion of 480 mg (4 mg /min over 60 minutes)
干预措施: PRT064445/Edoxaban (Combination Product)
Module 4 (800 mg bolus)
800 mg PRT064445 as a single IV bolus
干预措施: Placebo/Edoxaban (Combination Product)
Module 4 Placebo
Placebo administered intravenously (IV) as a bolus or a bolus followed by continuous infusion.
干预措施: Placebo (Drug)
结局指标
主要结局
Efficacy: Percent Change From Baseline in Anti-fXa Activity at 2 Mins Following Andexanet/Placebo Administration
时间窗: Baseline to 2 minutes following the end of andexanet/placebo administration
Anti-fXa activity was measured immediately prior to (Baseline) and at 2 mins following andexanet/placebo administration. Anti-fXa activity was measured using a commercial kit (Coamatic Heparin-82 33 9363, DiaPharma)
次要结局
- Andexanet Maximum Observed Plasma Concentration (Cmax)(Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.)
- Andexanet Area Under the Drug Concentration-time Curve From Time 0 Extrapolated to Infinity (AUC0-inf )(Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.)
- Andexanet Time of Maximum Observed Plasma Concentration (Tmax)(Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.)
- Andexanet Total Systemic Clearance (CL)(Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.)
- Efficacy: Percent Change From Baseline in Thrombin Generation at 2 Mins Following Andexanet/Placebo Administration(Baseline to 2 minutes following the end of andexanet/placebo administration)
- Efficacy: Percent Change From Baseline in Unbound Edoxaban Plasma Concentration at 2 Mins Following Andexanet/Placebo Administration(Baseline to 2 minutes following the end of andexanet/placebo administration)
- Andexanet Apparent Terminal Elimination Half-life (t1/2)(Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.)
- Andexanet Total Volume of Distribution (Vss)(Blood was collected at predose, 0.033, 0.2, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4.5, 5.5, 6.5, 7.5, 8.5 and 14.5 hours postdose.)