RT Journal Article
SR Electronic
T1 Bronchodilator effect of a novel inhaled dual PDE3/4 inhibitor, RPL554, in mild allergic asthma & rhinitis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P708
VO 42
IS Suppl 57
A1 Zuzana Diamant
A1 Lui Franciosi
A1 Nicoletta Morelli
A1 Rob Zuiker
A1 Ingrid Kamerling
A1 Marieke de Kam
A1 Koos Burggraaf
A1 Adam Cohen
A1 Michael Walker
A1 Clive Page
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/P708.abstract
AB Background: RPL554 is a novel inhaled dual phosphodiesterase (PDE) 3 & 4 inhibitor with long-acting bronchodilator & anti-inflammatory effects in preclinical models.Aims and Objectives: To evaluate RPL554 safety & efficacy in mild allergic asthma & rhinitis.Methods: In 2 randomised, double-blind, placebo-controlled, crossover trials, 10 mild allergic asthmatics (M; 20-50y; FEV1: 82-112%prd; PC20Mch: 0.07-1.49mg/mL; SABA prn only) and 10 allergic rhinitics (M; 19-44y; 6 with co-existing asthma; FEV1: 83-128%prd) were studied. In asthmatics, a methacholine challenge (PC20Mch) was done 1h from nebulisation start to assess bronchoprotection. Using a jet nebuliser, RPL554 0.018mg/kg was inhaled 10min via an oro-nasal mask. Standard safety & pharmacokinetic measurements were at predetermined times from nebulisation start with spirometry at pre-dose & regularly for 24h. Bronchodilation was assessed by FEV1 changes.Results: RPL554 was well-tolerated. Adverse events were mild, transient & generally of equal frequency in RPL554 & placebo groups with no significant changes in heart rate or systemic blood pressure noted. In asthmatics, RPL554 produced rapid, sustained bronchodilation, with a mean maximal FEV1 increase of 520mL (95%CI: 320-720mL; p<0.0001) or 15% increase from baseline vs. placebo. It also increased PC20MCh by mean 1.5 doubling doses (95%CI: 0.63– 2.3; p=0.004). In rhinitics, a maximal bronchodilator response occurred between 30min & 3h with a mean maximal FEV1 increase of 300mL or 7.5% increase (95%CI: 90-310mL; p=0.004).Conclusions: RPL554 produced safe, rapid, long-lasting bronchodilation in mild allergic asthmatics & rhinitics, with bronchoprotection in asthmatics.