Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD

Autor: Aida Emirova, Dave Singh, Marie Anna Nandeuil, Mirco Govoni, Henrik Watz, Brian Leaker, Oliver Kornmann, Silvia Geraci, Germano Lucci, Kai Michael Beeh, Brendan Colgan
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
Chronic bronchitis
Leukotriene B4
Placebo
Gastroenterology
03 medical and health sciences
chemistry.chemical_compound
Pulmonary Disease
Chronic Obstructive

0302 clinical medicine
Double-Blind Method
Internal medicine
medicine
para-Aminobenzoates
Humans
Induced sputum
Macrophage inflammatory protein
Aged
lcsh:RC705-779
Inflammation
Pharmacology
COPD
Sulfonamides
Cross-Over Studies
Dose-Response Relationship
Drug

business.industry
Research
Chronic obstructive pulmonary disease
Sputum
lcsh:Diseases of the respiratory system
Middle Aged
medicine.disease
Crossover study
Phosphodiesterase 4 inhibitors
Bronchodilator Agents
030104 developmental biology
Treatment Outcome
030228 respiratory system
chemistry
Tumor necrosis factor alpha
Female
medicine.symptom
Inflammation Mediators
business
Biomarkers
Zdroj: Respiratory Research
Respiratory Research, Vol 20, Iss 1, Pp 1-12 (2019)
ISSN: 1465-993X
Popis: Background CHF6001 is a novel inhaled phosphodiesterase-4 inhibitor. This Phase IIa study assessed the effects of CHF6001 on markers of inflammation in induced sputum and blood in patients with chronic obstructive pulmonary disease (COPD). Methods This was a multicentre, three-period (each 32 days), three-way, placebo-controlled, double-blind, complete-block crossover study. Eligible patients had COPD, chronic bronchitis, and were receiving inhaled triple therapy for ≥2 months. Patients received CHF6001 800 or 1600 μg, or matching placebo twice daily via multi-dose dry-powder inhaler (NEXThaler). Induced sputum was collected pre-dose on Day 1, and post-dose on Days 20, 26 and 32. Blood was sampled pre-dose on Day 1, and pre- and post-dose on Day 32. Results Of 61 randomised patients, 54 (88.5%) completed the study. There were no significant differences between groups for overall sputum cell count, or absolute numbers of neutrophils, eosinophils or lymphocytes. CHF6001 800 μg significantly decreased the absolute number and percentage of macrophages vs placebo. In sputum, compared with placebo both CHF6001 doses significantly decreased leukotriene B4, C-X-C motif chemokine ligand 8, macrophage inflammatory protein 1β, matrix metalloproteinase 9, and tumour necrosis factor α (TNFα). In blood, both CHF6001 doses significantly decreased serum surfactant protein D vs placebo. CHF6001 1600 μg significantly decreased TNFα ex-vivo (after incubation with lipopolysaccharide). Conclusion The data from this study show that CHF6001 inhaled twice daily has anti-inflammatory effects in the lungs of patients with COPD already treated with triple inhaled therapy. Trial registration The study is registered on ClinicalTrials.gov (NCT03004417). Electronic supplementary material The online version of this article (10.1186/s12931-019-1142-7) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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