RT Journal Article
SR Electronic
T1 LATE-BREAKING ABSTRACT: A Phase 1b study of PUR0200, a novel tiotropium formulation, in COPD patients
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP PA4365
DO 10.1183/13993003.congress-2015.PA4365
VO 46
IS suppl 59
A1 David Hava
A1 Katie Kane
A1 Fred Reid
A1 Arjun Ravi
A1 Jo Collier
A1 Tess Schmalbach
A1 Dave Singh
YR 2015
UL http://erj.ersjournals.com/content/46/suppl_59/PA4365.abstract
AB Rationale: PUR0200 is a tiotropium bromide formulation engineered in a novel dry powder delivery technology called iSPERSE. iSPERSE offers advantages over traditional technologies in enabling diverse classes of inhaled compounds with improved delivery efficiency to the lung. A Phase 1b study was designed to determine the pharmacokinetics (PK), pharmacodynamics (PD) and safety and tolerability of PUR0200 compared to Spiriva HandiHaler 18μg (HH) in COPD patients.Methods: A 2-part, single dose, placebo controlled dose-ranging study of PUR0200 was performed in moderate-to-severe COPD patients (n=38). The main phase of the study was a 5-period crossover design with 3 doses of PUR0200 (3, 6, or 9μg), placebo and HH 18μg. PK and FEV1 were assessed over 24h post-dose.Results: PUR0200 was well tolerated, with mainly mild adverse events. Absorption of PUR0200 was rapid with dose-proportional increases in C5min and AUCanalyses. Geometric values for C5min and AUC0-30min were similar between PUR0200 3μg and HH 18μg suggesting similar lung deposition. PUR0200 9μg resulted in a 4.5 times higher lung dose of tiotropium than HH 18μg. Statistically significant increases in FEV1 and FVC were observed for all PUR0200 doses compared to placebo. Similar FEV1 responses were observed for all PUR0200 dose levels when compared to HH [Mean (SD) FEV1 change from baseline AUC0-24h (h.L) PUR0200 3μg = 4.09 (2.89) and HH = 4.25 (3.44)].Conclusions: PUR0200 administration of tiotropium results in similar PK and PD to HH 18μg at significantly lower nominal doses, demonstrating the delivery advantages of the iSPERSE technology.