Evaluation of a Simple Pharmacokinetic Tool (myPKFiT™) to Guide Personalized Factor VIII Dosing in Patients With Hemophilia
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 39
- 主要终点
- Clearance (Cl)
研究概览
简要总结
This is an investigator-initiated, industry-funded, multi-centre, international study that will be carried out prospectively at hemophilia treatment centres across Canada, the Czech Republic and Australia with SickKids as the coordinating site. The study will use a central laboratory not directly affiliated with any of the participating sites. Enrollment target is 50 participants, both adult and pediatric with severe hemophilia A receiving Advate, who will each complete a 2-point and 6-point pharmacokinetic (PK) sampling. The main aim is to compare the results of a 2 sample PK using clinically practical time points and myPKFiT™ (a web-based, population PK Bayesian tool) to a 6 sample population PK to determine whether the results obtained are in good agreement.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed diagnosis of Hemophilia A;
- •Severe disease (FVIII <2%);
- •Receiving ADVATE for prevention of bleeding (prophylaxis) or receiving ADVATE on demand and a candidate for prophylaxis;
- •Body weight ≤120 kg; and ≥12kg;
排除标准
- •FVIII inhibitor positive (level of ≥0.6 Bethesda Units [BU] per mL using the Nijmegen modification of the Bethesda assay). Inhibitor status to be documented as negative prior to study enrollment according to the two most recent, consecutive inhibitor assays on record. If patients have < 50 exposure days, an assay will be completed centrally within a reasonable timeframe (approximately 8 weeks suggested) to make sure that they are negative.
- •Body weight >120 kg or <12kg;
- •Human immunodeficiency virus (HIV) positivity with cluster of differentiation 4 (CD4) count < 200 / microliter;
- •Significant hepatic dysfunction, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times upper limit of normal
- •History of recent events that might affect FVIII half-life (e.g., infection, surgery or an invasive procedure) within 2 weeks of blood sampling.
结局指标
主要结局
Clearance (Cl)
时间窗: 2 years
2-point PK sampling protocol against 6-point PK sampling protocol
Volume of distribution at steady state (Vss)
时间窗: 2 years
2-point PK sampling protocol against 6-point PK sampling protocol
Mean residence time (MRT)
时间窗: 2 years
2-point PK sampling protocol against 6-point PK sampling protocol
Time to factor VIII concentration of 1% over baseline
时间窗: 2 years
2-point PK sampling protocol against 6-point PK sampling protocol
In vivo recovery (IVR)
时间窗: 2 years
2-point PK sampling protocol against 6-point PK sampling protocol
Maximum concentration (Cmax)
时间窗: 2 years
2-point PK sampling protocol against 6-point PK sampling protocol
Terminal half-life (t1/2)
时间窗: 2 years
2-point PK sampling protocol against 6-point PK sampling protocol
Area under the moment curve (AUMC)
时间窗: 2 years
2-point PK sampling protocol against 6-point PK sampling protocol
area under the plasma concentration versus time curve (AUC)
时间窗: 2 years
2-point PK sampling protocol against 6-point PK sampling protocol
次要结局
未报告次要终点
研究者
Victor Blanchette
Medical Director, Pediatric Thrombosis and Hemostasis Program
The Hospital for Sick Children