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  4. Efficacy and safety of inhaled calcium lactate PUR118 in the ozone challenge model - a clinical trial
 
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2015
Journal Article
Title

Efficacy and safety of inhaled calcium lactate PUR118 in the ozone challenge model - a clinical trial

Abstract
Background: The ozone challenge model can be used to assess the efficacy of anti-inflammatory compounds in early phases of clinical drug development. PUR118, a calcium salt based formulation engineered in the iSPERSE (TM) dry powder delivery technology, is a novel anti-inflammatory drug for COPD. Here we evaluated the efficacy and safety of three doses of PUR118 in attenuating ozone-induced airway inflammation in healthy volunteers. Methods: In a single-blind, phase 1B proof of concept study, 24 subjects were enrolled to sequentially receive three doses of PUR118 (5.5 mg, n = 18; 11.0 mg, n = 18; 2.8 mg, n = 16). Each dose was inhaled 3 times (1, 13, 25 h, preceded by 2 puffs salbutamol) before the ozone exposure (250 ppb, 3 h intermittent exercise). Sputum was induced 3 h after the end of exposure. Results: Sputum neutrophils, sputum CD14+ cells, as well as concentrations of IL1B, IL6, IL8, MMP9, and TNFA in sputum supernatant significantly increased after ozone exposure (n = 24). The percentage of sputum neutrophils (n = 12 who completed all treatments) did not change following treatment with different doses of PUR118. The high dose treatment group (n = 16) showed a decrease in the percentage and number of sputum macrophages (p <= 0.05) as well as a decrease in blood neutrophils (p = 0.04), and an increase in blood CD14 + cells (p = 0.04) compared to baseline. All dosages of PUR118 were safe and well tolerated. Conclusion: Ozone challenge resulted in the expected and significant increase of sputum inflammatory parameters. Treatment with multiple rising doses of PUR118 was safe and three applications within 25 h prior to the ozone challenge had small effects on ozone-induced airway inflammation.
Author(s)
Holz, Olaf  
Biller, Heike
Müller, Meike  
Kane, Katie
Rosano, Molly
Hanrahan, John
Hava, David L.
Hohlfeld, Jens M.
Journal
BMC pharmacology & toxicology. Online journal  
Open Access
File(s)
Download (662.5 KB)
Rights
CC BY 4.0: Creative Commons Attribution
DOI
10.24406/publica-r-241858
10.1186/s40360-015-0021-1
Language
English
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
Keyword(s)
  • obstructive pulmonary disease

  • induced airway inflammation

  • healthy-volunteers

  • Inhalation

  • roflumilast

  • Antagonist

  • markers

  • pulmonary disease, chronic obstructive

  • COPD

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