Open AccessIntravenous Hydroxypropyl β‐Cyclodextrin Formulation of Letermovir: A Phase I, Randomized, Single‐Ascending, and Multiple‐Dose Trial
Author(s) -
ErbZohar K,
Kropeit D,
Scheuenpflug J,
Stobernack HP,
Hulskotte EGJ,
Schanke A,
Zimmermann H,
RübsamenSchaeff H
Publication year - 2017
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12483
Subject(s) - cmax , pharmacokinetics , dosing , placebo , medicine , adverse effect , single center , pharmacology , area under the curve , randomized controlled trial , alternative medicine , pathology
Letermovir is a novel antiviral in clinical development for prophylaxis against human cytomegalovirus in immunocompromised transplant recipients. This two‐part, single‐center, randomized, double‐blind, placebo‐controlled trial evaluated the safety and pharmacokinetics of a hydroxypropyl β‐cyclodextrin (HPβCD)‐based intravenous formulation of letermovir in healthy women. Subjects received single, escalating doses (120, 240, 480, 720, and 960 mg; 6 letermovir, 2 placebo per cohort) or multiple, once‐daily doses (240 mg; 8 letermovir, 4 placebo) of HPβCD‐formulated letermovir and the associated pharmacokinetic profiles and adverse events were investigated. Single‐dose and multiple‐dose regimens were generally well tolerated. Single‐dose escalation resulted in a slightly more‐than‐dose‐proportional increase in the area under the letermovir plasma concentration–time curve (AUC), whereas increase in the maximal observed letermovir plasma concentration (C max ) was dose proportional. After once‐daily dosing, accumulation ratios in AUC and C max were 1.22 and 1.03, respectively. The terminal half‐life was 28.3 h, supporting once‐daily dosing (EudraCT Number: 2012‐001603‐20).