TY - JOUR
T1 - A controlled trial of 6-weeks' treatment with a novel inhaled phosphodiesterase type-4 inhibitor in COPD
AU - Vestbo, J
AU - Tan, L
AU - Atkinson, G
AU - Ward, J
AU - NN, NN
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
KW - Administration, Inhalation
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Cyclic Nucleotide Phosphodiesterases, Type 4
KW - Double-Blind Method
KW - Female
KW - Forced Expiratory Volume
KW - Humans
KW - Male
KW - Middle Aged
KW - Nebulizers and Vaporizers
KW - Phosphodiesterase Inhibitors
KW - Placebos
KW - Pulmonary Disease, Chronic Obstructive
KW - Treatment Outcome
U2 - 10.1183/09031936.00068908
DO - 10.1183/09031936.00068908
M3 - Journal article
C2 - 19213793
SN - 1399-3003
SN - 0904-1850
VL - 33
SP - 1039
EP - 1044
JO - The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
JF - The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
IS - 5
ER -