Safety of ascending single and multiple doses of inhaled SIS, an isotonic aqueous solution of sodium hypochlorite, in healthy subjects

Abstract

Background: SIS is a novel aqueous formulation of sodium hypochlorite (NaOCl), which is present as hypochlorous acid (HOCl), a biological oxidant with broad spectrum antimicrobial activity in vitro.

Objectives & Methods: This single-centre, first-in-human, randomised, double-blind, placebo-controlled study was designed to explore the safety and tolerability of ascending single and multiple doses of inhaled SIS (NCT05188638). Subjects were randomised 3:1 to receive SIS formulations (HOCl concentrations 25 – 100 µg/mL) in single or multiple daily administrations (once to four times daily) for 5 days, or a matching placebo regimen.

Results: A total of N = 57 healthy subjects (age 27 ± 6 years, 60% male, 84% Caucasian, 98% not Hispanic or Latino, BMI 23.9 ± 2.9 kg/m2) were randomised to receive SIS (n = 43) or placebo (n = 14). One subject withdrew voluntarily from the study due to personal choice, unrelated to study treatment. There were no reported serious adverse events. A total of 18 adverse events were reported in 15 subjects (27.9% subjects receiving SIS and 21.4% subjects receiving placebo). Adverse events were predominantly mild. Solicited reporting of primarily mild local tolerability showed a dose-response relationship in SIS treated groups (0% assessments in the single dose 25 µg/mL formulation group to 14.2% assessments in the four times daily 100 µg/mL formulation group over 5 days). No dose-response effects on spirometry were observed.

Conclusions: SIS at concentrations of up to 100 µg/mL administered four times daily was safe and well tolerated, in this study population of healthy volunteers.