Pharmacokinetic Study of Raltegravir in Human Immunodeficiency Virus/Hepatitis C Virus (HIV/VHC) Coinfected Patients With Advanced (Child-Pugh C) Hepatic Cirrhosis (LIVERAL)
Phase I, Open Label, Unicentric Study of Multiple-dose Pharmacokinetics of Raltegravir in Patients Infected With Human Immunodeficiency Virus and Hepatitis C Virus With and Without Advanced (Child-Pugh C) Hepatic Cirrhosis.
Raltegravir is the first integrase inhibitor used in humans.
It has been shown to be highly efficacious and well tolerated in phase III clinical trials in multidrug experienced human immunodeficiency virus(HIV)-infected patients, as well as initial therapy in untreated patients.
Pharmacokinetic studies in healthy adult subjects indicate that the major mechanism of clearance of the drug is glucuronidation mediated by UGT1A1, with a minor contribution of renal excretion of unchanged parent compound.
Unlike CYP-based metabolism, glucuronidation is generally found to be relatively unaffected by hepatic disease.
A single dose pharmacokinetic study of raltegravir in patients with mild to moderate hepatic insufficiency (Steigbigel et al. 2008) found no clinically important effect on the drug pharmacokinetic profile, with no dosage adjustment being necessary.
The liver safety and tolerability of boosted atazanavir (ATV/r) has been evaluated in human immunodeficiency virus and hepatitis C virus (HIV/HCV) coinfected patients with advanced liver disease (decompensated cirrhosis) (Hermida JM et al. 4th IAS: Sidney, 2007).
Similar to Raltegravir, ATV is also mainly metabolized by conjugation through UGT1A1.
There is an urgent need for potent and efficacious ARV drugs with a clean safety liver profile even in patients with severe liver disease.
The investigators hypothesized that pharmacokinetics will not be altered in HIV/HCV patients with advanced (Child-Pugh grade C) cirrhosis or in those with no histologic liver damage.
研究概览
研究类型
介入性
注册 (实际的)
10
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Madrid、西班牙、28034
- Hospital Universitario Ramón y Cajal.
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- Adults, clinically stable HIV/HCV coinfected patients on HAART with controlled viremia (<50 copies/ml) for at least 6 months. HAART will be based on a boosted protease inhibitor (lopinavir, fosamprenavir or darunavir). Hepatic Stability is defined by the absence of new events of descompensation (Child-Pugh score) in the previous six weeks with no data of progressive hepatic insufficiency.
- Liver biopsy performed during the previous year showing no liver damage (F0-F1 in the Metavir score) or by elastometry results ≤ 6 Kpa, to classify patients in group B.
- Liver cirrhosis guided by biopsy (F4 in the Metavir score) or elastometry: results ≥ 14 Kpa, to classify patients in group A.
- Body mass index (BMI) in the range of 19-35 kg/m2.
Exclusion Criteria:
- HBV surface antigen positive.
- Clinical demonstration of a new descompensation event in the previous 6 weeks.
- Alcohol abuse as an average daily consumption > 20g.
- Treatment with boosted atazanavir, saquinavir or indinavir.
- Concomitant treatment with phenytoin, phenobarbital and rifampinor other UGT1A1 inhibitors.
- Use of any investigational agents (other than ART on expanded access) within 90 days of randomization.
- Active or previous HCV treatment with Ribavirin and /or Peg-interferon if sustained virological response achieved.
- Women taking oral contraceptives
- Pregnancy and lactancy.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：非随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：Patients with Child-Pugh C hepatic-cirrhosis.
VIH/VHC coinfected patients with advanced (Child-Pugh C) hepatic cirrhosis.
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有源比较器：VIH/VHC coinfected patients without liver damage.
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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The area under the curve (AUC0-12) calculated from plasma concentrations, the maximum concentration (Cmax) and the the minimum concentration (Cmin) of Raltegravir 400 mg/12 hours in the steady state for both arms.
大体时间：On the fifth day of treatment with raltegravir
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On the fifth day of treatment, patient will be hospitalized in the clinical trial unit in order to obtaine plasma concentrations previous to the administration of the corresponding dose (basal) and at the following times post-administration: 30min, 1h, 1h30min, 2h, 3h, 4h, 6h, 8h, and 12h.
With these measures, (AUC0-12), Cmax and Cmin will be calculated in order to describe the pharmacokinetic of Raltegravir 400 mgBID in the steady state in both arms
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On the fifth day of treatment with raltegravir
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Change from baseline in hematology and biochemistry parameters at day 5 and 15, number of adverse events (serious and non serious) notified and number of patients who discontinue the study (drop-out rate).
大体时间：On day 1, 5 and 15
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Hematology and biochemistry parameters, adverse events notified during the study and drop-out rate will be recorded in order to evaluate the safety and tolerability of multiple doses of raltegravir in HIV/HCV coinfected patients, with no liver damage and with advanced cirrhosis.
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On day 1, 5 and 15
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Santiago Moreno Guillen, MD、Hospital Universitario Ramón y Cajal. Madrid
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2010年12月1日
初级完成 (实际的)
2011年6月1日
研究完成 (实际的)
2011年10月1日
研究注册日期
首次提交
2011年2月1日
首先提交符合 QC 标准的
2011年2月3日
首次发布 (估计)
2011年2月4日
研究记录更新
最后更新发布 (估计)
2013年2月1日
上次提交的符合 QC 标准的更新
2013年1月31日
最后验证
2013年1月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- LIVERAL
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.