A Phase 1, Open-label Study to Compare the Pharmacokinetics and Pharmacodynamics of Warfarin and Esmolol in the Absence and Presence of MEDI0382 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Maximum international normalized ratio (INRmax)
研究概览
简要总结
A Phase 1 study to evaluate the effect of MEDI0382 on PK and PD of warfarin and esmolol in healthy subjects.
详细描述
This is a Phase 1 open label, one-sequence, crossover study to evaluate the effect of MEDI0382 on PK and PD of warfarin and esmolol in healthy subjects. The safety and tolerability of MEDI0382 in combination with warfarin and esmolol will also be evaluated. Following screening, the study consists of 2 5-day inpatient stays followed by outpatient visits.
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
- •Healthy volunteers aged ≥ 18 to 45 years
- •BMI between 18 -30 kg/m2
- •Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception
排除标准
- •Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product
- •Receipt of investigational product as part of a clinical study or a GLP-1 analogue containing preparation within the last 30 days or 5 half-lives of the drug (whichever is longer) at the time of screening.
- •Concurrent participation in another study of any kind
- •Severe allergy/hypersensitivity to any of the proposed study treatments or excipients.
- •History or presence of gastrointestinal (GI), hepatic, or renal disease or any other conditions known to interfere with absorption, distribution, metabolism or excretion of drugs.
- •Impaired renal function is defined as estimated glomerular filtration rate (eGFR) < 60 mL/minute/1.73 m2 at screening.
- •Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks of screening.
- •History of hemophilia, von Willebrand's disease, lupus anticoagulant, or other diseases/syndromes that can either alter or increase the propensity for bleeding.
研究组 & 干预措施
MEDI0382
All participants will receive MEDI0382.
干预措施: MEDI0382 (Biological)
Warfarin
All participants will receive Warfarin
干预措施: Warfarin (Drug)
Esmolol
All participants will receive Esmolol
干预措施: Esmolol (Drug)
结局指标
主要结局
Maximum international normalized ratio (INRmax)
时间窗: Days 2-8 and Days 27-33
To assess the AUC INR in the absence and presence of Warfarin on a steady state MEDI0382
Change in heart rate from resting after a 9-minute excercise treadmill test (Bruce Protocol, first 3 stages)
时间窗: Days 1 and 26
To assess the effects of MEDI0382 on the hear rate-lowering effect of esmolol during treadmill test.
次要结局
- PK(AUC) of R-Warfarin and S-Warfarin(Days 2 and 27)
- 12 lead electrocardiogram including RR, PR, QRS, QT and QTc intervals(Day 1, Day 8, Day 13, and Day 18)
- Vital signs (systolic and diastolic blood pressure)(Days 1-8, Days 12 and 13, Days 25-33)
- Clinical laboratory assessments (serum chemistry)(Day -1, Day 8, Day 17, Day 25 and Day 33)
- PK (Cmax) of R-Warfarin and S-Warfarin(Days 2 and 27)
- Anti-drug antibody titer incidence(Days 1 and 33)
- Clinical laboratory assessments (hematology)(Days 1 and 33)
- Clinical laboratory assessment (urinalysis)(Day -1)
- Number of patients with Adverse Events (AEs)(33 Days)
- Vital signs (pulse rate and respiratory rate(Days 1-8, Days 12 and 13, Days 25-33)