The pharmacokinetics, pharmacodynamics and tolerability of PUR0200, a novel tiotropium formulation, in chronic obstructive pulmonary disease.
AIMS
PUR0200 is a tiotropium bromide formulation engineered with the iSPERSE dry powder delivery technology. PUR0200 is being developed as a bioequivalent alternative to tiotropium bromide, delivered using Spiriva® HandiHaler® (HH). We investigated the bronchodilator effects, pharmacokinetics and safety of PUR0200 in patients with chronic obstructive pulmonary disease (COPD).


METHODS
This was a randomized, placebo-controlled, crossover study using different PUR0200 doses and the comparator tiotropium HH. In vitro aerodynamic particle size distribution (aPSD) characterization of PUR0200 and tiotropium HH are presented. The main endpoints included forced expiratory volume in 1 s (FEV1 ) trough and (0-24 h) and pharmacokinetic parameters.


RESULTS
The increased fine-particle fraction of PUR0200 demonstrated by testing using the next-generation impactor increased the proportion of drug available for lung deposition compared with the tiotropium HH. There was a numerical dose-response effect for PUR0200 on FEV1 , with 3 μg demonstrating a lower effect than higher doses. The placebo-adjusted mean (95% confidence interval) increases from baseline at 24 h postdose were 150 ml (100-200), 210 ml (160-270) and 200 ml (140-250) for 3 μg, 6 μg and 9 μg doses of PUR0200, respectively. Tiotropium HH (18 μg) caused a mean 169 ml (standard deviation 157ml) improvement in trough FEV1 , which was not significantly different to the PUR0200 effects at any of the tested doses.


CONCLUSIONS
PUR0200 treatment caused bronchodilation in COPD patients that was similar in magnitude to that caused by tiotropium HH. This enabled a similar clinical effect on lung function to be achieved with PUR0200 using a lower metered dose of tiotropium compared with tiotropium HH.
['Singh|Dave|D|0000-0001-8918-7075', 'Ravi|Arjun|A|', 'Kane|Katie|K|', 'Schmalbach|Tess|T|', 'Hava|David L|DL|']
D000280:Administration, Inhalation D000368:Aged D001993:Bronchodilator Agents D018592:Cross-Over Studies D004305:Dose-Response Relationship, Drug D004311:Double-Blind Method D058995:Dry Powder Inhalers D005260:Female D006801:Humans D008297:Male D008875:Middle Aged D029424:Pulmonary Disease, Chronic Obstructive D013147:Spirometry D013810:Therapeutic Equivalency D000069447:Tiotropium Bromide D016896:Treatment Outcome
pharmacokinetics PUR0200 tiotropium COPD FEV1