Safety of Ascending Single and Multiple Doses of Nebulised SoftOx Inhalation Solution in Healthy Subjects

Background: This first-in-human study will investigate the safety and tolerability of single and multiple doses of nebulised SoftOx Inhalation Solution (SIS) delivered via a jet nebuliser to healthy subjects. Objectives: The objective of the current study is to assess the safety and tolerability of single and multiple ascending doses of nebulised SIS in healthy subjects. Eligibility: Subjects are eligible to participate in this study if they are healthy, between 18 and 55 years of age, and have a Body Mass Index (BMI) of ≥ 18.5 and ≤ 29.9 kg/m2. Subjects are not eligible to participate in this study if they have recently participated in another clinical trial or have donated blood, have a medical condition or a history of drug hypersensitivity, are using concomitant medication, or have a positive drugs of abuse test. Design: A randomised, double-blind, and placebo-controlled trial. Subjects will be enrolled into one of three single dose groups or into one of four multiple dose groups. The two first multiple dose groups will be dosed once daily (OD) for five days. The two last multiple dose groups will be dosed twice daily (BID) for four days plus a morning dose on Day 5, or four times daily (QID) for four days plus a morning dose on Day 5, respectively. The investigational medicinal product (SIS or placebo; IMP) will be delivered via a jet nebuliser and inhaled through a mask over a period of up to 15 minutes. Each treatment group will comprise eight subjects who will be randomised to receive SIS or placebo in a 3:1 ratio. A Safety Monitoring Committee (SMC) will review the safety and tolerability data from all preceding groups and decide whether the planned next dose regimen is acceptable prior to initiating the dosing in a new dose group. The dose to be administered in the multiple dose groups will depend on the results obtained in the single dose groups and will be decided by the SMC. The dose tested in the first multiple dose group will be the second