A controlled trial of 6 weeks' treatment with a novel inhaled PDE₄ inhibitor in COPD

¹ North West Lung Centre, Wythenshawe Hospital / University of Manchester, Manchester, United Kingdom; and Medicines Evaluation Unit, Manchester, United Kingdom
² Clinical R&D, Pfizer Inc, Sandwich, United Kingdom

^* To whom correspondence should be addressed. E-mail: Jorgen.vestbo{at}manchester.ac.uk.

	Abstract

Anti-inflammatory drugs are lacking in COPD and inhibitors of the phosphodiesterase type-4 (PDE₄) enzyme have been suggested as an interesting class of drugs to treat inflammation in COPD. We report the findings of a Phase II trial of a novel inhaled PDE₄-inhibitor.

Three doses of the compound UK-500,001 were tested, 0.1mg, 0.4mg and 1mg twice daily (BID), in a double-blind placebo-controlled 6 week trial in 209 patients with moderate or severe COPD. The primary efficacy parameter was trough FEV₁ after 6 weeks of treatment, and secondary endpoints included other lung function endpoints, and symptom scores assessed at 2 weekly intervals. The study was stopped following a planned interim analysis for futility.

No effect was observed at any dose after 6 weeks of treatment on the primary efficacy parameter, other measures of lung function or symptom scores. However, after the first 2 weeks of treatment, there was an improvement in the 1mg BID dose group compared to placebo on a number of outcome measures. The drug was well tolerated although PDE₄-inhibitor related side effects were observed, especially in the highest dose group.

Our findings question the role of inhaled PDE₄-inhibitors in COPD.