Appraisal of MDCO-157 and Plavix® Pharmacokinetics and Pharmacodynamics in Healthy Volunteers With an Open-label, Randomized, Cross-over Evaluation: The AMPHORE Study
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Dose Response of MDCO-157 (3 doses) compared to Plavix 300 mg
研究概览
简要总结
Following a first, dose ascending study that enrolled 144 normal healthy volunteers (NHVs), this study, to be conducted in approximately 36 NHVs, will provide pertinent information in determining the dose-response of MDCO-157 for platelet aggregation inhibition and P2Y12 receptor inhibition effects and in selection of doses that match the antiplatelet effects of 300 mg PLAVIX® ®. The study will also provide additional data for pharmacokinetics (PK), safety and tolerability of single doses of MDCO-157.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 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
- 未提供
排除标准
- •Known or suspected hypersensitivity or allergy to clopidogrel, Captisol, PLAVIX® , or its excipients
- •Body mass index <20 or > 30 kg/m²
- •Inability to communicate with the investigator or comply with study related procedures, or high likelihood of being lost to follow up
- •Known or suspected pregnancy or lactating female
- •Medical history, physical examination including 12-lead ECG or laboratory evaluation conducted at the screening visit with results indicative of any disease or condition which might compromise the hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, or central nervous system; or other conditions that may interfere with the absorption, distribution, metabolism or excretion of study drug, or would place the subject at increased risk
- •Tobacco product use within the last 6 months prior to dosing
- •Platelet count < 150,000/µL
- •A personal or family history of coagulation or bleeding disorders or reasonable suspicion of vascular malformations
- •Active pathological bleeding such as peptic ulcer or intracranial hemorrhage
- •Positive screen for Hepatitis B (Hepatitis B Surface Antigen HBsAg), Hepatitis C (Hepatitis C Antibody), or HIV (anti-HIV 1/2)
- •Received an investigational drug within a period of 30 days or 5 half-lives, whichever is longer, prior to enrollment in the study
- •Use of aspirin, other non-steroidal anti-inflammatory drugs, CYP3A4 inhibitors (ketoconazole), CYP2C19 inhibitors (eg, omeprazole) or other drugs known to affect platelet function or coagulation within 14 days prior to receiving study drug (MDCO-157 or oral clopidogrel)
- •Grapefruit within 10 days prior to receiving study drug (MDCO-157 or PLAVIX®)
- •Use of any over-the-counter medication, including herbal products, within 7 days prior to administration of study drug (MDCO-157 or PLAVIX®), except for up to 2 grams of acetaminophen per day for up to 3 days for pain control
研究组 & 干预措施
75mg MDCO-157
iv
干预措施: MDCO-157 (Drug)
150mg MDCO-157
iv
干预措施: MDCO-157 (Drug)
300mg MDCO-157
iv
干预措施: MDCO-157 (Drug)
300mg PLAVIX
oral
干预措施: PLAVIX (Drug)
结局指标
主要结局
Dose Response of MDCO-157 (3 doses) compared to Plavix 300 mg
时间窗: 24 hr
To evaluate the dose-response of MDCO-157 (at 3 doses) compared to Plavix (300 mg), using Emax and AUEC with VASP, over 24 hours: * Maximum effect of P2Y12 receptor inhibition (Emax) using VASP (flow cytometry) * Area under the effect of P2Y12 receptor inhibition time curve (AUEC) using VASP (flow cytometry)
次要结局
- Pharmacokinetics (PK) of MDCO-157 and its metabolites(24 hrs)
- Safety and tolerability(48 hrs post each treatment period)
- Dose response of MDCO-157 as assessed by LTA(24 hours)
- Dose response of MDCO-157 as assess by VerifyNow P2Y12 assay(24 hours)