NCT03397888已完成1 期
The Effect o f Hepatic Impairment on the Pharmacokinetics and Pharmacodynamics of Betrixiban, an Oral FXa Antagonist
Portola Pharmaceuticals1 个研究点 分布在 1 个国家目标入组 32 人开始时间: 2017年11月16日最近更新:
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- PK - Tmax
研究概览
简要总结
Single center, prospective open label PK and PD study of betrixaban in subjects with mild and moderate hepatic impairment vs healthy volunteers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Cohorts 1 & 2: Man or a woman 18 to 70 with stable chronic hepatic impairment disease due to cirrhosis confirmed by biopsy, ultrasound, CT or MRI (Cohort 1 - Mild impairment, Child-Pugh Category A; Cohort 2 - Moderate Impairment, Child-Pugh Category B). Cohort 3: essentially healthy man or woman without liver disease whose sex, age and weight match patients in Cohorts 1 & 2 in order to result in similar average demographics.
- •Body Mass Index between 18 and 35 kg*m-2 and weighs at least 50 kg.
- •Contraception. Men must agree to acceptable methods of contraception. Women of child-bearing potential must agree to two acceptable forms of contraception. Post-menopausal women must have had no regular menstrual bleeding for at least one year prior to initial dosing and confirmed by an elevated plasma Follicle-stimulating hormone level test at screening for women not in receipt of hormone replacement therapy (HRT). Women who report surgical sterilization must have had the procedure at least six months prior to dosing, supported by clinical documentation.
- •The subject has clinical unremarkable medical history, physical examination, ECG, laboratory values and vital signs, as determined by the investigator. Subjects in Cohorts 1 & 2 may have: abnormal liver function tests, INR up to 2.2, PT up to 6 seconds over control, aPPT up to 45 seconds and platelets down to 45,000/uL.
- •The subject smokes <12 cigarettes per day or equivalent and agrees to no or reduced tobacco products while domiciled.
- •The subject is able to read and give written informed consent and signed the IRB approved consent form.
- •The subject has adequate venous access for blood sampling.
排除标准
- •The subject has a history, symptoms of, or risk factors for bleeding or a stool specimen within 6 months of dosing positive for occult blood.
- •The subject has an absolute/relative contraindication to anticoagulation due to: history of intracranial bleeding, severe active bleeding, recent brain, eye, or spinal cord surgery or major surgery within 6 months of dosing.
- •The subject has a history of or risk factors for a hypercoagulable or thrombotic condition.
- •The subject has a history of any clinically significant cardiac, endocrinologic, hematologic, hepatic (except for Cohorts 1 & 2), immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal or other major disease other than the underlying disease in Cohorts 1 &
- •The subject has a calculated creatinine clearance of <60mL/min as determined by Cockcroft-Gault method.
- •Concomitant medication use:
- •For all subjects, illicit drugs, oral contraceptives, and hormone replacement therapy are excluded within 30 days prior to Day -
- •For all subjects, over the counter drugs, including dietary supplements and herbal products are excluded within 14 days prior to Day -
- •Subjects enrolled in Cohort 3 will be excluded if the subject has taken any prescription drugs in the 30 days prior to dosing. Furthermore, the subject will be excluded if he/she does not agree to refrain from concomitant drugs throughout the study unless medically necessary as determined by the Investigator.
- •Subjects enrolled in Cohort 1 and 2 may continue taking stable preexisting medications throughout the study with the exception of strong P-gp inhibitors. Strong P-gp inhibitors include but are not limited to: amiodarone, azithromycin, clarithromycin, erythromycin, ketoconazole, and verapamil. Prescribed stable acetaminophen use up to 2,000 mg per day is allowable. Any acetaminophen use with alcohol within 48 hours of dosing is prohibited. Furthermore, the subject will be excluded if he/she does not agree to refrain from additional concomitant drugs throughout the study unless medically necessary as determined by the Investigator.
- •The subject has a history of severe trauma or bone fracture within 6 months prior to dosing; or planned surgery within 1 month after dosing.
- •The subject has a history of blood donation of more than 500mL within 3 months prior to dosing.
- •The subject has received an investigational drug product within 30 days or 5 half-lives of the investigational compound, whichever is greater, from Day -
- •The subject has positive screen for drugs of abuse at Day -
- •The subject does not agree to withhold from alcohol consumption from 48 hours prior to dosing through discharge.
- •The subject has a medical or surgical condition which may impair drug absorption.
- •The subject is pregnant or breastfeeding.
- •The subject has any condition which could interfere with or for which the treatment might interfere with the conduct of the study, or would, in the opinion of the Investigator, increase the risk of the subject's participation in the study.
研究组 & 干预措施
Cohort 1
Experimental
Mild Impairment, Child-Pugh Category A
干预措施: Betrixaban (Drug)
Cohort 2
Experimental
Moderate Impairment, Child-Pugh Category B
干预措施: Betrixaban (Drug)
Cohort 3
Experimental
Essentially Healthy man or woman without liver disease matched to Cohorts 1 & 2 for age, sex and weight.
干预措施: Betrixaban (Drug)
结局指标
主要结局
PK - Tmax
时间窗: Day 1 through Day 6
Time to maximum observed plasma concentration (Tmax).
PK - AUC (0-last)
时间窗: Day 1 through Day 6
Area under the plasma concentration-time curve from 0 to last measurable concentration (AUC (0-last)).
PK - Plasma half-life (t1/2)
时间窗: Day 1 through Day 6
Plasma half-life (t1/2), distribution half-life and terminal half-life.
PK - (AUC(0-∞)).
时间窗: Day 1 through Day 6
Total area under the plasma concentration-time curve from time 0 to infinity (AUC(0-∞)).
PK - Cmax
时间窗: Day 1 through Day 6
Maximum observed plasma concentration (Cmax)
PK - Volume of distribution
时间窗: Day 1 through Day 6
Apparent volume of distribution (Vd/F).
PK - Total clearance
时间窗: Day 1 through Day 6
Apparent total clearance (CL/F).
次要结局
- Safety - 12 Lead ECG - PR(Day -30 through up to Day 21)
- Safety - Treatment Emergent AEs(Day -1 through up to Day 21)
- Safety - Demographics(Day -30 through Day -2 (Screening))
- Safety - Vital Signs Temperature(Day -30 through up to Day 21)
- Safety - Vital Signs Blood Pressure(Day -30 through up to Day 21)
- Safety - Vital Signs Heart Rate(Day -30 through up to Day 21)
- Safety - 12 Lead ECG - WRS(Day -30 through up to Day 21)
- Safety - Lab - Hematology - Platelet Count(Day -30 through up to Day 21)
- Safety - Lab - Hematology - Lymphocytes(Day -30 through up to Day 21)
- Safety - Lab - Hematology - Mean Corpuscular Hemoglobin Volume(Day -30 through up to Day 21)
- Safety - Lab - Hematology - Monocytes(Day -30 through up to Day 21)
- Safety - Vital Signs Respiratory Rate(Day -30 through up to Day 21)
- Safety - Lab - Hematology - white blood cell [WBC](Day -30 through up to Day 21)
- Safety - Lab - Hematology - Eosinophil's(Day -30 through up to Day 21)
- Safety- Lab - Coagulation - PT(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Potassium(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Glucose(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Blood Urea Nitrogen(Day -30 through up to Day 21)
- Safety - Lab - Urinalysis - Specific Gravity(Day -30 through up to Day 21)
- Safety - 12 Lead ECG - RR(Day -30 through up to Day 21)
- Safety - Physical Exam - Height(Day -30 through up to Day 21)
- Safety - Lab - Hematology - Mean Corpuscular Hemoglobin Concentration(Day -30 through up to Day 21)
- Safety- Lab - Coagulation - aPTT(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Creatinine(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - AST(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - ALT(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Albumin(Day -30 through up to Day 21)
- Safety - Lab - Urinalysis - Nitrate(Day -30 through up to Day 21)
- Safety - 12 Lead ECG - QT(Day -30 through up to Day 21)
- Safety - Physical Exam - Weight(Day -30 through up to Day 21)
- Safety - Lab - Hematology - hemoglobin(Day -30 through up to Day 21)
- Safety - Lab - Hematology - hematocrit(Day -30 through up to Day 21)
- Safety - Lab - Hematology - Absolute Basophils(Day -30 through up to Day 21)
- Safety - Lab - Hematology - Neutrophils(Day -30 through up to Day 21)
- Safety- Lab - Coagulation - INR(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Sodium(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Alkaline Phosphatase(Day -30 through up to Day 21)
- Safety - Lab - Blood Virology - HIV II(Day-30 through Day -2 (Screening))
- PD - Anti-Factor Xa Concentration(Day 1 through Day 6)
- PD - Thrombin Concentrations(Day 1 through Day 6)
- Safety - 12 Lead ECG - QTcF(Day -30 through up to Day 21)
- Safety - 12 Lead ECG - QTcB(Day -30 through up to Day 21)
- Safety - Lab - Hematology - Absolute Neutrophil Count(Day -30 through up to Day 21)
- Safety - Lab - Hematology - Mean Corpuscular Hemoglobin(Day -30 through up to Day 21)
- Safety- Lab - Coagulation - Factor V Leiden(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Chloride(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Carbon Dioxide(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - GGT(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Total Protein(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Calcium(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Uric Acid(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - LDH(Day -30 through up to Day 21)
- Safety - Lab - Hematology - Red Blood Cell Count(Day -30 through up to Day 21)
- Safety - Lab - Hematology - Red Cell Distribution Width(Day -30 through up to Day 21)
- Safety - Lab - Hematology - Reticulocyte(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Phosphorus(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Total Bilirubin(Day -30 through up to Day 21)
- Safety - Lab - Urine toxicology Panel - Ethanol(Day -30 through Day -1)
- Safety - Lab - Urine toxicology Panel - Opiates(Day -30 through Day -1)
- Safety - Lab - Blood Virology - HIV I(Day-30 through Day -2 (Screening))
- Safety - Lab - Blood Virology - Hepatitis C(Day-30 through Day -2 (Screening))
- Safety - Lab - Urinalysis - Protein(Day -30 through up to Day 21)
- Safety - Lab - Serum Chemistry - Fractionated Bilirubin(Day -30 through up to Day 21)
- Safety - Lab - Urine toxicology Panel - Amphetamines(Day -30 through Day -1)
- Safety - Lab - Urine toxicology Panel - Barbiturates(Day -30 through Day -1)
- Safety - Lab - Urine toxicology Panel - Cannabinoids(Day -30 through Day -1)
- Safety - Lab - Urine toxicology Panel - Cocaine(Day -30 through Day -1)
- Safety - Lab - Urinalysis - pH(Day -30 through up to Day 21)
- Safety - Lab - Urinalysis - Glucose(Day -30 through up to Day 21)
- Safety - Lab - Urinalysis - Hemoglobin(Day -30 through up to Day 21)
- Safety - Lab - Urinalysis - Leukocyte esterase(Day -30 through up to Day 21)
- Safety - Fecal Occult Blood Testing(Day -30 through Day -2 (screening))
- Safety - Lab - Blood Virology - Hepatitis B(Day-30 through Day -2 (Screening))
- Safety - Lab - Serum Pregnancy(Day -30 through up to Day 21)
- Safety - Urine Occult Blood Testing(Day -30 through Day -2 (screening))
研究者
研究点 (1)
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