Background: OligoG is a low molecular-weight alginate oligosaccharide that improves the viscoelastic properties of CF mucus and disrupts biofilms, thereby potentiating the activity of antimicrobial agents. The efficacy of inhaled OligoG was evaluated in adult patients with cystic fibrosis (CF). Methods: A randomized, double-blind, placebo-controlled multi-centre cross-over study was used to demonstrate safety and efficacy of inhaled dry powder OligoG. Subjects were randomly allocated to receive OligoG 1050mg per day (10 capsules TID) or matching placebo for 28-days, with 28-day washout periods following each treatment period. The primary endpoint was absolute change in percent predicted FEV1 at the end of 28-day treatment. The ITT population (N=65) was defined as randomised to treatment with at least one administration of study medication and post-dosing evaluation.Results:Ninety adult subjects were screened and 65 randomized. Statistically significant improvement in FEV1 was not observed in the ITT population. Adverse events (AEs) included nasopharyngitis, cough and pulmonary exacerbation. The number and proportions of patients with AEs and SAEs were similar between OligoG and placebo group.Conclusions: Inhalation of OligoG-DPI over 28-days was safe in adult CF subjects. Statistically significant improvement of FEV1 was not reached. The planned analyses did not indicate a significant treatment benefit with OligoG compared to placebo. Post-hoc exploratory analyses showed subgroup results which indicate that further studies of OligoG in this patient population are justified.