A controlled trial of 6-weeks' treatment with a novel inhaled phosphodiesterase type-4 inhibitor in COPD
J Vestbo, L Tan, G Atkinson, J Ward, UK-500,001 Global Study Team, J C Figuero Casas, A Echazarreta, E Giugno, O E Rizzo, M C De Salvo, P Bardin, M Phillips, J P Seale, P Thompson, G R Bailey, D S Helmersen, K J Killian, D E M O'Donnell, S Chernilo, R Sepúlveda, F Pavicic, N Tudoric, M Kasl, V Kolek, J Musil, E Csanky, M Namenyi, Z Mark, R Alvarez, P De Lucas, J Vestbo, J Vestbo, L Tan, G Atkinson, J Ward, UK-500,001 Global Study Team, J C Figuero Casas, A Echazarreta, E Giugno, O E Rizzo, M C De Salvo, P Bardin, M Phillips, J P Seale, P Thompson, G R Bailey, D S Helmersen, K J Killian, D E M O'Donnell, S Chernilo, R Sepúlveda, F Pavicic, N Tudoric, M Kasl, V Kolek, J Musil, E Csanky, M Namenyi, Z Mark, R Alvarez, P De Lucas, J Vestbo
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.
Trial registration: ClinicalTrials.gov NCT00263874.
Source: PubMed