Pharmacokinetics of Oral Letermovir in Adults With End-Stage Kidney Disease With or Without Haemodialysis

Official title

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

Overview

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.

Interventions

• Drug Letermovir 480 mg [PREVYMIS]
  A single 480 mg oral dose of letermovir (2 x 240 mg tablets).

Primary outcome measures

• Area Under the plasma concentration-time Curve (AUC) of letermovir [Time frame: Pre-dose to 48 hours post-dose]

Eligibility criteria

Inclusion criteria

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.

Group 1:

• Adult participants (≥18 years old).
• Estimated Glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2.
• 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.

Group 2:

• Adult participants (≥18 years old).
• Estimated Glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2.
• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07101055 · UQ117254-Letermovir

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗