Safety, tolerability, and pharmacokinetics of topical NB-001 (0.1%, 0.3%, and 0.5%) for the treatment of recurrent herpes labialis

Abstract

METHODS 0 (0.0%) 1 (0.8%) 0 (0.0%) 0 (0.0%) Subjects with Serious AEs 0 (0.0%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Subjects with AEs leading to discontinuation of drug 1 (0.9%) 0 (0.0%) 1(0.9%) 0 (0.0%) Subjects with drug-related AEs 7 (6.0%) 8 (6.6%) 9 (7.8%) 8 (6.2%) 2 (2.7%) 1 (0.8%) 0 (0.0%) 0 (0.0%) Application Site Reaction 4 (3.4%) 2 (1.7%) 1 (0.9%) 0 (0.0%) Second Herpes Lesion 7 (6.0%) 9 (7.4%) 11 (9.5%) 13 (10.1%) Nasopharyngitis 4 (3.4%) 1 (0.8%) 0 (0.0%) 1 (0.8%) Headache 1 (0.9%) 3 (2.5%) 3 (2.6%) 0 (0.0%) Shoulder Pain 3 (2.6%) 0 (0.0%) 0 (0.0%) 0 (0.0%) Background: NB-001 is a topically applied oil-in-water emulsion containing high energy nanometer-sized droplets that permeate skin pores and hair follicles to enter the epidermis and dermis where they kill virus on contact. At 180 nm, the droplets are excluded by tight junctions between epithelial cells and thus do not disrupt tissue matrices or enter blood vessels. This minimizes skin irritation and systemic absorption. We assessed the reported adverse events (AEs) including skin irritation and systemic drug absorption of 3 concentrations of NB-001 (0.1%, 0.3% and 0.5%) compared to vehicle. Method: 484 subjects with recurrent herpes labialis were randomized to NB-001 (0.1%, 0.3%, 0.5%) or vehicle. Subjects applied 200 µL of medication 5 times daily for a maximum of 4 days. Safety, including dermal irritation, was evaluated daily by AE query. A subset of subjects had pharmacokinetic sampling following application of medication to an open lesion (Day 3 �1 day). Samples were analyzed for circulating levels of a marker for the nanoemulsion using a validated HPLC method (limit of detection 1 ng/mL). Results: 482 subjects started treatment and were included in the safety population. There were no deaths, no serious AEs, no significant drug-related AE and no subjects to moderate in severity and as expected for this population. The most commonly reported AE was a second cold sore lesion, reported in 8% of subjects. Overall, all active treatments were well tolerated with only 1 subject in the 0.1% NB-001 group reporting application site irritation. There were negligible levels of active ingredient detected in plasma samples following topical application of NB-001, indicating a lack of systemic absorption. Conclusions: There were no significant safety or dermal irritation concerns in any of the treatment groups and pharmacokinetic sampling indicated no significant systemic absorption. NB-001 is safe and well tolerated in subjects with recurrent herpes labialis.