Bioequivalence Study of Crushed Sofosbuvir/Velpatasvir Compared to the Whole Tablet
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 试验地点
- 3
- 主要终点
- AUC
研究概览
简要总结
Epclusa® is a pan-genotypic, once-daily tablet for the treatment of chronic hepatitis C virus (HCV) infection containing the NS5B- polymerase inhibitor sofosbuvir (SOF, nucleotide analogue) 400 mg and the NS5A inhibitor velpatasvir (VEL) 100 mg.
For patients with swallowing difficulties, administration of whole tablets can be problematic. In addition, HCV patients that are hospitalized (at intensive care units) due to severe illness (co-infections/ liver failure) might not be able to swallow medication. Therefore it is useful to know whether it is possible to administer SOF/VEL through a different route, like a feeding tube.
In daily practice, information about the safety and efficacy of crushed tablets is lacking which might result in interruption or discontinuation of expensive HCV therapy. However, it is not recommended to interrupt treatment because there is no evidence about the efficacy of the therapy after discontinuation (and restart).
Currently, patients and healthcare professionals are crushing SOF/VEL tablets without information about efficacy and safety. Depending on the biopharmaceutical characteristics of a drug formulation, crushing tablets can lead to altered pharmacokinetics of drugs.
It is important to know whether pharmacokinetic parameters are influenced by crushing of tablets; both a decrease and an increase in exposure may occur. A decrease of the plasma concentrations of SOF and/or VEL potentially reduces the therapeutic effect of the drugs. Higher doses or switching to other HCV-drugs might be needed. In contrast, in case a higher Cmax,ss and/or exposure occurs there might be an increased risk of toxicity.
As a result, crushing the drug is a contra-indication based on the available data.
Therefore this study will be conducted to investigate whether a crushed SOF/VEL tablet is bioequivalent to SOF/VEL as a whole tablet.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with SOF/VEL treatment for the treatment of chronic HCV genotype 1 through
- •Patient is at least 18 at the day of screening.
- •Patient is able and willing to sign the Informed Consent Form.
- •Patient is able and willing to follow protocol requirements.
排除标准
- •Pregnant female (as confirmed by an hCG urine test performed at screening) or breast-feeding female.
- •Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
- •Inability to understand the nature and extent of the study and the procedures required.
- •Clinically relevant low hemoglobin concentration at screening judged by the patient's own hepatologist.
研究组 & 干预措施
sofosbuvir/velpatasvir tablet
Single-dose sofosbuvir/velpatasvir as a whole tablet in a fasted state.
干预措施: sofosbuvir/velpatasvir tablet (Drug)
sofosbuvir/velpatasvir crushed
Single-dose crushed sofosbuvir/velpatasvir in a fasted state.
干预措施: sofosbuvir/velpatasvir crushed (Drug)
结局指标
主要结局
AUC
时间窗: Up to 24 hours after administration
Cmax
时间窗: one dosing interval after administration of SOF/VEL (up to 24 hours)
次要结局
- Adverse events(During the entire conduct of the study, maximum of two weeks)