title: A controlled trial of 6-weeks' treatment with a novel inhaled phosphodiesterase type-4 inhibitor in COPD.
abstract: Anti-inflammatory drugs are lacking in chronic obstructive pulmonary disease (COPD) and inhibitors of the phosphodiesterase type-4 (PDE4) enzyme have been suggested to be an interesting class of drugs to treat inflammation in COPD. The present authors report the findings of a phase II trial of a novel inhaled PDE4 inhibitor. Three doses, 0.1, 0.4 and 1.0 mg b.i.d., of the compound UK-500,001 were tested in a double-blind, placebo-controlled, 6-week trial in 209 patients with moderate-to-severe COPD. The primary efficacy parameter was trough forced expiratory volume in one second after 6 weeks of treatment, and secondary end-points included other lung function end-points and symptom scores assessed at 2-week intervals. The present study was stopped following a planned interim analysis for futility. No effect on the primary efficacy parameter, other measures of lung function or symptom scores was observed at any dose of UK-500,001 after 6 weeks of treatment. However, after the first 2 weeks of treatment, an improvement in a number of outcome measures in the 1.0 mg b.i.d. dose group was observed compared with placebo. The drug was well tolerated, although PDE4 inhibitor-related side-effects were observed, especially in the highest dose group. The findings of the present study question the role of inhaled phosphodiesterase type-4 inhibitors in chronic obstructive pulmonary disease.
authors.affiliation: North West Lung Centre, Wythenshawe Hospital, Manchester, UK. Jorgen.vestbo@manchester.ac.uk
authors.forename: J
authors.initials: J
authors.lastname: Vestbo
authors.forename: L
authors.initials: L
authors.lastname: Tan
authors.forename: G
authors.initials: G
authors.lastname: Atkinson
authors.forename: J
authors.initials: J
authors.lastname: Ward
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009330:Nebulizers and Vaporizers; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010919:Placebos; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D010726:Phosphodiesterase Inhibitors; D010919:Placebos; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4