A Prospective, Open-Label, Single-Centre, Comparative Pharmacokinetic Study of Oral Letermovir (PREVYMIS) in Patients (i) Undergoing Intermittent Haemodialysis and (ii) Not Undergoing Intermittent Haemodialysis
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 20
- 主要终点
- Area Under the plasma concentration-time Curve (AUC) of letermovir
研究概览
简要总结
This study aims to understand how the antiviral medication letermovir (PREVYMIS) is processed by the body in adults with end-stage kidney disease (ESKD), including those who are receiving intermittent haemodialysis and those who are not. Letermovir is already approved in many countries, including Australia, for preventing cytomegalovirus (CMV) infections in patients who have received stem cell transplants. However, its pharmacokinetics - or how the drug is absorbed, distributed, and cleared from the body - have not been studied in patients with ESKD, especially those on dialysis.
This is a single-centre, open-label, interventional pharmacokinetic study. It will recruit 20 adult participants, split into two groups: 10 participants on intermittent haemodialysis and 10 not undergoing dialysis. All participants will receive a single oral dose of 480 mg letermovir. The study does not involve treatment for CMV infection. Instead, it focuses only on how the drug behaves in the body in this patient population.
Participants will have blood samples collected before and after taking the medication to measure drug concentrations over time. In patients on dialysis, an additional sample will be taken from the dialysis machine to understand if letermovir is removed during treatment. No more than 35 mL of blood (around two tablespoons) will be collected across two study visits.
The goal of this study is to generate important safety and dosing information to help guide future use of letermovir in people with kidney failure. It is expected that these findings will support more informed clinical decisions and potentially lead to updated dosing recommendations for this group.
The study is funded by Merck Sharp & Dohme LLC (MSD), the manufacturer of letermovir, and is being conducted by researchers from The University of Queensland Centre for Clinical Research (UQCCR) and the Royal Brisbane and Women's Hospital (RBWH). To support participation, prepaid meal vouchers, taxi vouchers, or parking tickets will be provided so that participants do not incur any out-of-pocket expenses.
Participation is voluntary. The study has been approved by a Human Research Ethics Committee and is conducted according to national ethical guidelines.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 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
- 是
入选标准
- •All participants of childbearing potential who are engaging in sexual activity that could result in pregnancy must be willing to use highly effective contraception from screening through 30 days post-dose of letermovir. Male participants must also agree not to donate sperm during this period.
- •Adult participants (≥18 years old).
- •Estimated Glomerular filtration rate (eGFR) < 15 mL/min/1.73 m
- •Clinical indication for regular intermittent haemodialysis.
- •Agreement to receive a single 480 mg dose of letermovir.
- •Willing and able to provide informed consent.
- •Consent to cannula placement for blood draws.
- •Adult participants (≥18 years old).
- •Estimated Glomerular filtration rate (eGFR) < 15 mL/min/1.73 m
- •No clinical indication for regular intermittent haemodialysis.
- •Agreement to receive a single 480 mg dose of letermovir.
- •Willing and able to provide informed consent.
- •Consent to cannula placement for blood draws.
排除标准
- •Participants who lack the capacity to provide informed consent.
- •Patients with suspected or known hypersensitivity to any of the active or inactive ingredients of the oral letermovir formulation.
- •Patients who are taking any of the following medications, unless these can be safely discontinued temporarily for the duration of the study as determined by the study investigator: statins (pitavastatin, simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin) and proton pump inhibitors (omeprazole, pantoprazole).
- •Patients who are taking any of the following medications: cyclosporine, pimozide, ergot alkaloids, or drug metabolism inducers including amiodarone, nafcillin, warfarin, carbamazepine, phenobarbital, phenytoin, glyburide, voriconazole, rifabutin, rifampicin, pimozide, thioridazine, bosentan, St. John's Wort, efavirenz, etravirine, nevirapine, sirolimus, tacrolimus, modafinil, CYP2C8 substrates (e.g., repaglinide, rosiglitazone), or CYP3A substrates (e.g., alfentanil, fentanyl, midazolam, quinidine).
- •Patients with severe hepatic impairment.
- •Pregnant, planning to conceive, breastfeeding, or intending to breastfeed during the study period.
- •Presence of any rapidly progressing disease or immediately life-threatening illness (i.e., death deemed imminent within 48 hours).
- •Any condition or circumstance that, in the investigator's opinion, would compromise patient safety or the integrity of study data.
研究组 & 干预措施
ESKD undergoing intermittent haemodialysis
Participants with end-stage kidney disease (ESKD) who are receiving regular intermittent haemodialysis. Each participant receives a single oral dose of letermovir (480 mg) approximately 2 hours before their scheduled dialysis session.
干预措施: Letermovir 480 mg [PREVYMIS] (Drug)
ESKD not undergoing intermittent haemodialysis
Participants with end-stage kidney disease (ESKD) who are not receiving haemodialysis. Each participant receives a single oral dose of letermovir (480 mg).
干预措施: Letermovir 480 mg [PREVYMIS] (Drug)
结局指标
主要结局
Area Under the plasma concentration-time Curve (AUC) of letermovir
时间窗: Pre-dose to 48 hours post-dose
The AUC will be calculated using non-compartmental analysis based on serial plasma concentration measurements following a single oral dose of letermovir. The aim is to compare systemic exposure between participants with end-stage kidney disease who are undergoing intermittent haemodialysis and those who are not.
次要结局
未报告次要终点
研究者
Jason A Roberts
Professor
The University of Queensland