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

: Holz, Olaf; Biller, Heike; Müller, Meike; Kane, Katie; Rosano, Molly; Hanrahan, John; Hava, David L.; Hohlfeld, Jens M.

Fulltext urn:nbn:de:0011-n-3695802 (662 KByte PDF)
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Created on: 10.5.2016

BMC pharmacology & toxicology. Online journal 16 (2015), Art. 21, 10 pp.
ISSN: 2050-6511
Journal Article, Electronic Publication
Fraunhofer ITEM ()
obstructive pulmonary disease; induced airway inflammation; healthy-volunteers; Inhalation; roflumilast; Antagonist; markers; pulmonary disease, chronic obstructive; COPD

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.