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Efficacy and safety of the oral p38 inhibitor PH-797804 in chronic obstructive pulmonary disease: a randomised clinical trial
  1. William MacNee1,
  2. Richard J Allan2,
  3. Ieuan Jones2,
  4. Maria Cristina De Salvo3,
  5. Lisa F Tan2
  1. 1Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
  2. 2Department of Clinical Research, Pfizer Global Research and Development, Sandwich, UK
  3. 3Centro Medico Dra. De Salvo, Buenos Aires, Argentina
  1. Correspondence to Dr Lisa F Tan, Department of Clinical Research, Pfizer Global Research and Development, Field House, Field Road, Kingston, Cambridge CB23 2NQ, UK; lisa.tan{at}


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.

  • COPD Pharmacology

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