Introduction: For many surgical procedures, surgical site infections (SSI) are much too common and are increasingly caused by highly virulent and multi-drug resistant microorganisms. An additional approach to SSI prevention is needed. E-101 Solution is a topical antimicrobial intended for application within a surgical wound to prevent SSI. It is novel both in terms of its mechanism of action and its intended use. The enzymatic activity of glucose oxidase produces a steady state of hydrogen peroxide which enables porcine myeloperoxidase (p-MPO) in E-101 Solution to catalyze the oxidation of chloride to hypochlorous acid and tyrosine to the tyrosyl radical and the disproportionation of hydrogen peroxide to singlet oxygen. These end-products are highly microbicidal against bacteria, viruses, fungi, yeasts, and prions in a concentration-dependent and time-dependent fashion. In animal models, E-101 Solution is considered safe, causing no deleterious effects on wound healing when administered directly into an experimental surgical wound.

Background: Prior to clinical testing of E-101 Solution on patients who are at high risk for SSI, it is necessary to ascertain its safety in healthy adult volunteers. Evaluation of the skin irritation potential of E-101 Solution is considered an important indicator of topical drug safety.

Methods: A well-accepted, FDA-recommended cumulative irritation Phase 1A study protocol was used to assess the safety of E-101 Solution during and after 21 consecutive days of topical exposure at dosage levels of 100 GU/mL and 300 GU/mL, compared to that of both 0.9% physiological saline (negative control) and 0.1% sodium lauryl sulfate (positive control). This study was subject-blinded and evaluator-blinded. A total of 30 subjects received all four treatments applied to both abraded and non-abraded target skin sites. Safety was assessed by visual inspection and scoring of skin irritation using a standardized irritation scoring scale, monitoring for adverse events, and laboratory tests.

Results: The table summarizes the mean cumulative irritation produced by the study drugs.

Study Test Article	Mean Cumulative Irritation Score: Non-Abraded Skin	Mean Cumulative Irritation Score: Abraded Skin
Physiological saline (negative control)	13.90	20.63
E-101 Solution – 100 GU/mL	18.23	25.53
E-101 Solution – 300 GU/mL	20.10	32.33
Sodium lauryl sulfate (positive control)	38.77	47.80

Skin irritation scores from abraded and non-abraded skin were lower (p < 0.05) in response to E-101 Solution exposure than those of the positive control. All notable E-101 Solution-related skin reactions were completely resolved within 48 hours after the last drug exposure. There were no clinically significant adverse patterns evident from conventional laboratory safety tests among the treated subjects and no adverse events.

Conclusions: The results of a conventional cumulative irritation Phase 1 study demonstrate E-101 Solution to be safe for application to human skin.