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Inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study

BACKGROUND: OligoG is a low molecular-weight alginate oligosaccharide that improves the viscoelastic properties of cystic fibrosis (CF) mucus and disrupts biofilms, thereby potentiating the activity of antimicrobial agents. The efficacy of inhaled OligoG was evaluated in adult patients with CF. METH...

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Autores principales: van Koningsbruggen-Rietschel, Silke, Davies, Jane C., Pressler, Tacjana, Fischer, Rainald, MacGregor, Gordon, Donaldson, Scott H., Smerud, Knut, Meland, Nils, Mortensen, Jann, Fosbøl, Marie Ø., Downey, Damian G., Myrset, Astrid H., Flaten, Hugo, Rye, Philip D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: European Respiratory Society 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569163/
https://www.ncbi.nlm.nih.gov/pubmed/33123558
http://dx.doi.org/10.1183/23120541.00132-2020
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author van Koningsbruggen-Rietschel, Silke
Davies, Jane C.
Pressler, Tacjana
Fischer, Rainald
MacGregor, Gordon
Donaldson, Scott H.
Smerud, Knut
Meland, Nils
Mortensen, Jann
Fosbøl, Marie Ø.
Downey, Damian G.
Myrset, Astrid H.
Flaten, Hugo
Rye, Philip D.
author_facet van Koningsbruggen-Rietschel, Silke
Davies, Jane C.
Pressler, Tacjana
Fischer, Rainald
MacGregor, Gordon
Donaldson, Scott H.
Smerud, Knut
Meland, Nils
Mortensen, Jann
Fosbøl, Marie Ø.
Downey, Damian G.
Myrset, Astrid H.
Flaten, Hugo
Rye, Philip D.
author_sort van Koningsbruggen-Rietschel, Silke
collection PubMed
description BACKGROUND: OligoG is a low molecular-weight alginate oligosaccharide that improves the viscoelastic properties of cystic fibrosis (CF) mucus and disrupts biofilms, thereby potentiating the activity of antimicrobial agents. The efficacy of inhaled OligoG was evaluated in adult patients with CF. METHODS: A randomised, double-blind, placebo-controlled multicentre crossover study was used to demonstrate safety and efficacy of inhaled dry powder OligoG. Subjects were randomly allocated to receive OligoG 1050 mg per day (10 capsules three times daily) or matching placebo for 28 days, with 28-day washout periods following each treatment period. The primary end-point was absolute change in percentage predicted forced expiratory volume in 1 s (FEV(1)) at the end of 28-day treatment. The intention-to-treat (ITT) population (n=65) was defined as randomised to treatment with at least one administration of study medication and post-dosing evaluation. RESULTS: In this study, 90 adult subjects were screened and 65 were randomised. Statistically significant improvement in FEV(1) was not observed in the ITT population. Adverse events included nasopharyngitis, cough and pulmonary exacerbation. The number and proportions of patients with adverse events and serious adverse events were similar between OligoG and placebo group. CONCLUSIONS: Inhalation of OligoG-dry powder over 28 days was safe in adult CF subjects. Statistically significant improvement of FEV(1) 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 that indicate that further studies of OligoG in this patient population are justified.
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spelling pubmed-75691632020-10-28 Inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study van Koningsbruggen-Rietschel, Silke Davies, Jane C. Pressler, Tacjana Fischer, Rainald MacGregor, Gordon Donaldson, Scott H. Smerud, Knut Meland, Nils Mortensen, Jann Fosbøl, Marie Ø. Downey, Damian G. Myrset, Astrid H. Flaten, Hugo Rye, Philip D. ERJ Open Res Original Articles BACKGROUND: OligoG is a low molecular-weight alginate oligosaccharide that improves the viscoelastic properties of cystic fibrosis (CF) mucus and disrupts biofilms, thereby potentiating the activity of antimicrobial agents. The efficacy of inhaled OligoG was evaluated in adult patients with CF. METHODS: A randomised, double-blind, placebo-controlled multicentre crossover study was used to demonstrate safety and efficacy of inhaled dry powder OligoG. Subjects were randomly allocated to receive OligoG 1050 mg per day (10 capsules three times daily) or matching placebo for 28 days, with 28-day washout periods following each treatment period. The primary end-point was absolute change in percentage predicted forced expiratory volume in 1 s (FEV(1)) at the end of 28-day treatment. The intention-to-treat (ITT) population (n=65) was defined as randomised to treatment with at least one administration of study medication and post-dosing evaluation. RESULTS: In this study, 90 adult subjects were screened and 65 were randomised. Statistically significant improvement in FEV(1) was not observed in the ITT population. Adverse events included nasopharyngitis, cough and pulmonary exacerbation. The number and proportions of patients with adverse events and serious adverse events were similar between OligoG and placebo group. CONCLUSIONS: Inhalation of OligoG-dry powder over 28 days was safe in adult CF subjects. Statistically significant improvement of FEV(1) 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 that indicate that further studies of OligoG in this patient population are justified. European Respiratory Society 2020-10-19 /pmc/articles/PMC7569163/ /pubmed/33123558 http://dx.doi.org/10.1183/23120541.00132-2020 Text en Copyright ©ERS 2020 http://creativecommons.org/licenses/by-nc/4.0/This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.
spellingShingle Original Articles
van Koningsbruggen-Rietschel, Silke
Davies, Jane C.
Pressler, Tacjana
Fischer, Rainald
MacGregor, Gordon
Donaldson, Scott H.
Smerud, Knut
Meland, Nils
Mortensen, Jann
Fosbøl, Marie Ø.
Downey, Damian G.
Myrset, Astrid H.
Flaten, Hugo
Rye, Philip D.
Inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study
title Inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study
title_full Inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study
title_fullStr Inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study
title_full_unstemmed Inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study
title_short Inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study
title_sort inhaled dry powder alginate oligosaccharide in cystic fibrosis: a randomised, double-blind, placebo-controlled, crossover phase 2b study
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569163/
https://www.ncbi.nlm.nih.gov/pubmed/33123558
http://dx.doi.org/10.1183/23120541.00132-2020
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