PT  - JOURNAL ARTICLE
AU  - William MacNee
AU  - Richard J Allan
AU  - Ieuan Jones
AU  - Maria Cristina De Salvo
AU  - Lisa F Tan
TI  - Efficacy and safety of the oral p38 inhibitor PH-797804 in chronic obstructive pulmonary disease: a randomised clinical trial
AID  - 10.1136/thoraxjnl-2012-202744
DP  - 2013 Aug 01
TA  - Thorax
PG  - 738--745
VI  - 68
IP  - 8
4099  - http://thorax.bmj.com/content/68/8/738.short
4100  - http://thorax.bmj.com/content/68/8/738.full
SO  - Thorax2013 Aug 01; 68
AB  - Rationale Chronic obstructive pulmonary disease (COPD) is a common lung disease leading to progressive decline in lung function. Inhibition of release of inflammatory mediators by p38 inhibitors may be a useful treatment for chronic inflammation of the airways thought to underlie the pathogenesis of the disease. Objectives To evaluate the efficacy and safety of PH-797804, a potent and selective p38 inhibitor, in adults with moderate to severe COPD (Global Initiative for Chronic Obstructive Lung Disease stage II/III). Methods This was a randomised, adaptive design, double-blind, placebo-controlled, parallel-group, multicentre trial. Patients were initially randomised to placebo, 0.5, 3, 6 or 10 mg PH-797804 once daily and treated for 6 weeks following a 2-week run-in. Measurements and main results The primary endpoint was change from baseline in trough forced expiratory volume in 1 s (FEV1) compared with placebo after 6 weeks of treatment. Secondary endpoints included other spirometric parameters, transition dyspnoea index, rescue mediation use, high sensitivity C-reactive protein and symptoms. A total of 230 patients were assigned to treatment; placebo (n=45), 0.5 mg (n=20), 3 mg (n=47), 6 mg (n=70) and 10 mg (n=48). PH-797804 showed a statistically significant improvement in trough FEV1 at week 6 compared with placebo of 0.086 litre (95% Bayesian CI 0.008 to 0.164) and 0.093 litre (95% CI 0.018 to 0·166) at 3 and 6 mg PH-797804, respectively. PH-797804 3 mg and 6 mg showed an improvement in the baseline dyspnoea index/transition dyspnoea index total focal score at week 6. PH-797804 was well tolerated at all doses studied. Conclusions PH-797804 demonstrated improvements over placebo in lung function parameters and dyspnoea in patients with moderate to severe COPD. TrialRegNo NCT00559910.