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

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.