Pharmacokinetics (PK) and Safety of Intravenous (IV) Brincidofovir (BCV) in Healthy Adult Subjects

Abstract

Poster Abstracts • OFID 2017:4 (Suppl 1) • S311 9). Nasal specimens were used to detect clinical and colonizing pathogens using the Diatherix TEM-PCR Respiratory Panel. Results. A total of 90 recruits were enrolled in the study. Twelve recruits were lost due to training attrition in the first week of the study. The participants were male and the mean age was 23 yo (SD 4.9). There were 10 (13%) cases of ILI reported among the 78 remaining participants, 6 in week 1, 3 in week 2 and 1 in week 9. The most frequently detected pathogens in the 10 symptomatic cases were coronavirus (5, 50%), rhinovirus (4, 40%), other enterovirus (3, 30%), and influenza A (2, 20%). Pathogen co-detections were common, 8 out 10 cases were associated with 2 pathogens, representing 7 unique combinations. While rhinovirus and coronavirus were most common among asymptomatic trainees, 10% had detectable influenza A. Detection of multiple pathogens was common in the first two weeks of training (50% among those who had viral detection). The study is still in progress. Conclusion. Symptomatic ILI was associated with coronavirus, rhinovirus, and enterovirus, in addition to influenza in the early weeks of training. Coronavirus and rhinovirus also circulated widely among healthy recruits, along with influenza. The findings will inform ILI control strategies for congregated military trainees. Background. BCV is a lipid conjugate nucleotide that has shown rapid viral clearance in patients with adenovirus infection and improved survival in animal models of smallpox. In preclinical studies in rats, IV BCV dosed twice weekly for up to 29 days was not associated with gastrointestinal (GI), hematopoietic, hepatic, or renal toxicity. This study evaluated the safety and PK of IV BCV in healthy subjects. Methods. In this double-blind study, subjects were randomized 3:1 to receive IV BCV or placebo in sequential single ascending dose cohorts (Table 1). Plasma PK samples were collected over 7 days and assayed by HPLC-MS. Plasma BCV PK parameters were determined by non-compartmental analysis and dose proportionality was assessed. Safety assessments were collected over 14 days. Results. Forty healthy male subjects (18-46 years, 83% White) were enrolled and completed the study. Plasma BCV Cmax and AUC∞ increased in proportion to dose (Table 1). AEs and alanine aminotransferase (ALT) elevations were dose-and infusion duration-related (Table 1). GI AEs were mild. All AEs and ALT elevations were transient a…