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Respir Med. 2009 Aug;103(8):1159-66. doi: 10.1016/j.rmed.2009.02.011. Epub 2009 Mar 16.

Safety, pharmacodynamics and pharmacokinetics of TPI 1020 in smokers with asthma.

Author information

1
Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Québec, QC G1V 4G5, Canada. lpboulet@med.ulaval.ca

Abstract

BACKGROUND:

TPI 1020 is a novel compound with potential for anti-neutrophil effects. TPI 1020 exerts its effects by a dual mechanism of action involving corticosteroid activity and controlled donation of nitric oxide.

OBJECTIVES:

We assessed the safety, pharmacodynamic and pharmacokinetic activity of ascending doses of TPI 1020 compared to budesonide in asthma.

METHODS:

Smokers with mild asthma (n=27) were randomized to receive either 600mcg of TPI 1020 (n=13) or 400mcg of budesonide (n=14) bid for 2weeks followed by 1200 and 800mcg bid, respectively, for an additional week.

RESULT:

There was no serious adverse event and all but one adverse event were mild or moderate (severe headache with budesonide). Patients receiving TPI 1020 reported three-fold fewer treatment-emergent AEs (n=13) than those receiving budesonide (n=39). TPI 1020 had similar effects as budesonide on FEV(1), PEF, rescue medication, asthma scoring system, methacholine response, sputum eosinophils and exhaled NO. Sputum neutrophils (%) tended to decrease more with TPI 1020 (32.6% decrease versus 3.7% increase for budesonide); the decrease occurring only in patients with high neutrophils at baseline. A significant difference favoring TPI 1020 was noted for CRP. Budesonide caused a statistically significant decrease in 24h urinary free cortisol over 22days (median of 4.4-2.8mcg/ml, p=0.01) whereas TPI 1020 had no such effect (4.4-5.8mcg/ml), suggesting lower systemic corticosteroid exposure following TPI 1020 treatment.

CONCLUSION:

TPI 1020 appears safe in asthmatic smokers and warrants further investigation in respiratory conditions.

PMID:
19286361
DOI:
10.1016/j.rmed.2009.02.011
[Indexed for MEDLINE]
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