A First-in-Human Phase 1 Study to Assess Safety, Tolerability and Pharmacokinetics of a Novel Antifungal Drug VL-2397 in Healthy Adults.

A First-in-Human Phase 1 Study to Assess Safety, Tolerability and Pharmacokinetics of a Novel Antifungal Drug VL-2397 in Healthy Adults.

Antimicrob Agents Chemother. 2019 Aug 19;:

Authors: Mammen MP, Armas D, Hughes FH, Hopkins AM, Fisher CL, Resch PA, Rusalov D, Sullivan SM, Smith LR

Abstract
VL-2397 is an antifungal drug with a novel mechanism of action, rapid fungicidal in vitro activity, and potent in vivo activity against Aspergillus fumigatus, including azole-resistant strains. VL2397-101, a phase 1 first-in-human, randomized, double-blind, placebo-controlled dose-escalation study was conducted in healthy adults to determine the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous (IV) doses of VL-2397. All dosing cohorts were fully enrolled; all subjects completed the safety follow-up. A safety committee reviewed the safety data for each dosing cohort prior to recommending the initiation of each subsequent cohort. No serious adverse events (SAEs) occurred; the majority of treatment-emergent adverse events (TEAEs) were mild and self-limited. The most common drug-related TEAEs were infusion site reactions. No clinically-concerning trends were noted in vital signs, electrocardiograms, physical examinations or safety laboratory results. Following single infusions of VL-2397 the overall and maximum exposures rose less than proportionally with increasing doses from 3 mg to 1200 mg as indicated by AUC24 and Cmax No signs of VL-2397 accumulation were observed following IV infusions of 300, 600 and 1200 mg Q24H for 7 days. Renal elimination plays a major role in total body clearance with up to 47% of unmetabolized drug in urine 24 hours after administration at single doses > 30 mg. Overall, VL-2397 dosing in the study appeared to be safe and well tolerated in the healthy subjects. The safety profile, consistent PK and lack of drug accumulation support further development of VL-2397 in patients with invasive aspergillosis.

PMID: 31427299 [PubMed – as supplied by publisher]

Source: Industry