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Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD.
Respir Res 2019; 20(1):180RR

Abstract

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).

Authors+Show Affiliations

Medicines Evaluation Unit, The University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK.Insaf Respiratory Research Institute, Wiesbaden, Germany.Celerion, Belfast, UK.IKF Pneumologie Frankfurt, Clinical Research Centre Respiratory Diseases, Frankfurt, Germany.The Heart Lung Centre, London, UK.Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research, Grosshansdorf, Germany.Global Clinical Development, Chiesi, Parma, Italy.Global Clinical Development, Chiesi, Parma, Italy.Global Clinical Development, Chiesi, Parma, Italy.Global Clinical Development, Chiesi, Parma, Italy. M.Govoni@chiesi.com.Global Clinical Development, Chiesi, Parma, Italy.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31399091

Citation

Singh, Dave, et al. "Effect of the Inhaled PDE4 Inhibitor CHF6001 On Biomarkers of Inflammation in COPD." Respiratory Research, vol. 20, no. 1, 2019, p. 180.
Singh D, Beeh KM, Colgan B, et al. Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD. Respir Res. 2019;20(1):180.
Singh, D., Beeh, K. M., Colgan, B., Kornmann, O., Leaker, B., Watz, H., ... Nandeuil, M. A. (2019). Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD. Respiratory Research, 20(1), p. 180. doi:10.1186/s12931-019-1142-7.
Singh D, et al. Effect of the Inhaled PDE4 Inhibitor CHF6001 On Biomarkers of Inflammation in COPD. Respir Res. 2019 Aug 9;20(1):180. PubMed PMID: 31399091.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of the inhaled PDE4 inhibitor CHF6001 on biomarkers of inflammation in COPD. AU - Singh,Dave, AU - Beeh,Kai Michael, AU - Colgan,Brendan, AU - Kornmann,Oliver, AU - Leaker,Brian, AU - Watz,Henrik, AU - Lucci,Germano, AU - Geraci,Silvia, AU - Emirova,Aida, AU - Govoni,Mirco, AU - Nandeuil,Marie Anna, Y1 - 2019/08/09/ PY - 2019/06/12/received PY - 2019/07/23/accepted PY - 2019/8/11/entrez PY - 2019/8/11/pubmed PY - 2019/8/11/medline KW - Chronic obstructive pulmonary disease KW - Induced sputum KW - Inflammation KW - Pharmacology KW - Phosphodiesterase 4 inhibitors SP - 180 EP - 180 JF - Respiratory research JO - Respir. Res. VL - 20 IS - 1 N2 - 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). SN - 1465-993X UR - https://www.unboundmedicine.com/medline/citation/31399091/Effect_of_the_inhaled_PDE4_inhibitor_CHF6001_on_biomarkers_of_inflammation_in_COPD_ L2 - https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-019-1142-7 DB - PRIME DP - Unbound Medicine ER -