First‐in‐Human, Single‐ and Multiple‐Ascending‐Dose, Food‐Effect, and Absolute Bioavailability Trials to Assess the Pharmacokinetics, Safety, and Tolerability of Pritelivir, a Nonnucleoside Helicase‐Primase Inhibitor Against Herpes Simplex Virus in Healthy Subjects

• Published in: Clinical pharmacology in drug development 2023-07, Vol.12 (7), p.749-760
• Main Authors: Kropeit, Dirk, Bonsmann, Susanne, Richter, Oliver, McCormick, David, Pausch, Jörg, Sumner, Melanie, Birkmann, Alexander, Zimmermann, Holger, Rübsamen‐Schaeff, Helga
• Format: Article
• Language: English
• Subjects: absolute bioavailability; Bioavailability; Biological Availability; DNA Primase; Female; first in human; food effect; Healthy Volunteers; Herpes viruses; Humans; MAD; Male; nonnucleoside helicase‐primase inhibitor; Pharmacokinetics; Plasma; pritelivir; SAD; Simplexvirus
• ISSN: 2160-763X; 2160-7648
• DOI: 10.1002/cpdd.1241

The pharmacokinetics and safety of the novel herpes simplex virus helicase‐primase inhibitor pritelivir were evaluated in 5 phase 1 trials: a single‐ascending‐dose trial, 2 multiple‐ascending‐dose trials, a food‐effect trial, and an absolute bioavailability trial in healthy male subjects. One cohort of healthy female subjects was included in the single‐ascending‐dose trial. Pritelivir pharmacokinetics were linear up to 480 mg following single and up to 400 mg following multiple once‐daily doses. The half‐life ranged from 52 to 83 hours, and steady state was reached between 8 and 13 days. Maximum plasma concentration and area under the plasma concentration–time curve from time 0 to the last quantifiable concentration were 1.5‐ and 1.1‐fold higher in female compared to male subjects. Absolute bioavailability was 72% under fasted conditions. Following a fatty diet, pritelivir time to maximum concentration was 1.5 hour delayed and maximum plasma concentration and area under the plasma concentration–time curve from time 0 to the last quantifiable concentration were 33% and 16% higher, respectively. Pritelivir was safe and well tolerated up to 600 mg following single and up to 200 mg following multiple once‐daily doses. Considering a therapeutic dose of 100 mg once‐daily, pritelivir demonstrated a favorable safety and tolerability and pharmacokinetic profile in healthy subjects to support further development.