Abstract | BACKGROUND: 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.
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Authors | Louis-Philippe Boulet, Catherine Lemière, Gail Gauvreau, Ron Olivenstein, Diane Lougheed, Bruno Paradis, Paul O'Byrne, René Pageau, Paolo M Renzi |
Journal | Respiratory medicine
(Respir Med)
Vol. 103
Issue 8
Pg. 1159-66
(Aug 2009)
ISSN: 1532-3064 [Electronic] England |
PMID | 19286361
(Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- NCX 1020
- Nitric Oxide
- Budesonide
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Topics |
- Adolescent
- Adult
- Aged
- Anti-Inflammatory Agents
(administration & dosage, adverse effects, pharmacokinetics)
- Asthma
(drug therapy)
- Budesonide
(administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
- Dose-Response Relationship, Drug
- Double-Blind Method
- Female
- Forced Expiratory Volume
(drug effects)
- Humans
- Male
- Middle Aged
- Neutrophil Activation
(drug effects)
- Nitric Oxide
(metabolism)
- Sputum
(cytology)
- Treatment Outcome
- Young Adult
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